Neurochem. Res. [JOURNAL]
Sun
200 papers
Naringenin-Loaded PCL Nanoparticles Attenuate Glial Activation and TNF-α Expression in Iron-Induced Post-traumatic Epilepsy.
Rabidas SS, Prakash C, Bhati S … +3 more , Bhattacharya J, Saran S, Sharma D
Neurochem Res · 2026 Feb · PMID 41729347 · Publisher ↗
Post-traumatic epilepsy (PTE) is the consequence of traumatic brain damage (TBI), which poses an important health risk for the human population. The underlying mechanism of PTE is complex and appears to be linked with va...
Post-traumatic epilepsy (PTE) is the consequence of traumatic brain damage (TBI), which poses an important health risk for the human population. The underlying mechanism of PTE is complex and appears to be linked with various cellular processes, including oxidative stress and neuroinflammation. Over the years, it has been recognized that most of the available antiseizure medicines are ineffective in preventing PTE. As a result, there is an urgent need to search for alternate treatment options. Naringenin is a flavonoid with multiple pharmacological properties and has shown beneficial effects in several health issues, including neurological disorders. In this study, we investigated the effect of naringenin-loaded polycaprolactone nanoparticles (NarNPs) on neuroinflammatory response in the PTE model. NarNPs were produced using the nanoprecipitation method, and their physicochemical properties were examined by DLS, TEM and AFM. To induce epilepsy in rats, FeCl3 was injected intracortically, and naringenin (NAR), both free NAR and NarNPs, were administered orally, 15 days post-surgery. Epileptic seizures were observed by electroencephalography (EEG) patterns and spectral power analysis of γ-waves. Immunofluorescence analysis of GFAP, IBA1 and TNF-α was performed to examine the disease-modifying potential of NarNPs. Our findings demonstrated that NarNPs marginally reduced epileptiform seizure activity in epileptic rats. Further, the study reported that NarNPs lowered the expression of GFAP, IBA1, and TNF-α. Overall, our data imply that NarNPs have antiseizure and disease-modifying potential by attenuating glial activation and TNF-α production in PTE rats.
Targeting the Microbiota-Gut-Brain Axis: Bacillus coagulans Protects Against Rotenone-Induced Parkinson's Disease in Rats.
Rout M, Prusty SK, Singh V … +3 more , Kispotta S, Sarangi P, Kar DM
Neurochem Res · 2026 Feb · PMID 41729340 · Publisher ↗
Gut microbiota and its derived metabolites affect brain physiology through several pathways. Dysfunction of gut-microbiota is involved in the pathogenesis of Parkinson's disease (PD). Introduced the pleiotropic effect of...
Gut microbiota and its derived metabolites affect brain physiology through several pathways. Dysfunction of gut-microbiota is involved in the pathogenesis of Parkinson's disease (PD). Introduced the pleiotropic effect of probiotics (PBT) in the function of the central nervous system, can delay the disease progression through microbiota-gut-brain axis (MGBA). PD is characterized by aggregated alpha-synuclein (α-syn), oxidative stress and neuroinflammation leading to depletion of dopaminergic neurons in the midbrain region. Our study designed to assess the neuroprotective effect of PBT Bacillus coagulans (B. coagulans) against rotenone (ROT) induced PD rats. To eliminate hormone-based errors associated with estrous cycle, we only used male rats in this experiment. ROT (50 mg/kg/day) caused perturbation of intestinal barrier leading to gut microbiome disturbances along with accumulation of α-syn in intestine and brain with motor deficits. qPCR of gut homogenate interpreted that treatment with B. coagulans alter the gut microbial composition in experimental PD through MGBA. This formulation claims as a supportive agent to restore the progression and aid in the therapeutic management of PD.
Effects of Electroacupuncture Stimulation on Motor Function Recovery in Mice After Spinal Cord Injury by Regulating Astrocyte Activation.
Zhong HZ, Cheng L, Tian DS … +4 more , Jiang Y, Jing JH, Wu ZH, Zhou Y
Neurochem Res · 2026 Feb · PMID 41729337 · Publisher ↗
Although it has been shown that electroacupuncture (EA) can regulate the activation of astrocytes, forming a stable microenvironment for nerve cell survival, and participating in the repair of spinal cord injury (SCI), t...
Although it has been shown that electroacupuncture (EA) can regulate the activation of astrocytes, forming a stable microenvironment for nerve cell survival, and participating in the repair of spinal cord injury (SCI), the underlying mechanisms are not fully understood. The study aimed to investigate the effects of EA stimulation on motor function recovery in mice after SCI by regulating astrocyte activation, and explore the involvement and regulatory role of Hippo-YAP signaling pathway. In this study, we established T10 thoracic SCI model by clip compression technique, and applied EA at Jiaji points on both sides of the spine at T12 and L2 levels at 6 h after model establishment. The results showed that compared with the SCI group, the EA group showed significantly higher BMS scores at 7, 14 and 28 days post-injury, and better hindlimb motor function recovery at 28 days after SCI (P < 0.05). An improvement in the degree of inflammatory reaction, the extent of glial scar formation, and the atrophy of neurons, an increase in the number of Nissl bodies, a decrease in karyorrhexis were observed in the EA group at different time points post-injury. The EA group showed significantly decreased expression of inflammatory factors (IL-1β, TNF-a and IL-6), GFAP and CSPGs, increased expression of p-MST1 and p-YAP, decreased expression of MST1 and YAP, increased p-MST1/MST1 ratio and p-YAP/YAP ratio than the SCI group at each time point post-injury (all P < 0.05). The EA group also showed significantly up-regulated expression of ZO-1, CLN-5, 5-HT and NFH, significantly increased density of NeuN-positive neurons and significantly decreased expression of CS56, CD68 compared to the SCI group at 14 days post-injury (all P < 0.05). Our findings suggest that EA stimulation may down-regulate the activation level of the astrocytes by activating the Hippo-YAP signaling pathway and decreasing the transcriptional activity of its downstream effector YAP, thus inhibiting the formation of glial scar and the release of inflammatory factors, enhancing the repair of the blood-spinal cord barrier, facilitating neuron survival and axon regeneration, leading to improvement in the recovery of hindlimb motor function in mice after SCI.
Transcranial Photobiomodulation Modulates Oxidative Stress Biomarkers and Complex IV Activity in Anhedonic-Like Behavior.
Bortoluzzi L, Colombo R, da Motta Pinto KB … +12 more , Viscardi LH, Missiaggia R, Turella DJ, Schwantess L, Salvador M, Branco CS, Rigotti M, Scotton E, Schons T, Ribeiro SB, Caldieraro MA, Rosa AR
Neurochem Res · 2026 Feb · PMID 41721935 · Full text
Major depressive disorder (MDD) is a prevalent and complex condition with limited treatment success in many patients. Photobiomodulation (PBM), particularly transcranial PBM (tPBM) using red to near-infrared light, has e...
Major depressive disorder (MDD) is a prevalent and complex condition with limited treatment success in many patients. Photobiomodulation (PBM), particularly transcranial PBM (tPBM) using red to near-infrared light, has emerged as a promising non-invasive intervention. However, optimal parameters and precise mechanisms remain unclear. This research aimed to analyze the effects of transcranial photobiomodulation (red and infrared) on behavioral and biological parameters related to MDD in a chronic mild stress (CMS) model. Male Wistar rats were exposed to CMS for five weeks and subsequently categorized into two groups-resilient (CMS-R) and susceptible (CMS-S)-based on their performance in the sucrose consumption test (SCT). The CMS-S group was further divided into three subgroups: (1) sham treatment, (2) tPBM red (600 nm), and (3) tPBM infrared (840 nm). A control group of non-stressed animals was included for baseline comparisons. Biological measures included lipid damage (TBARS), antioxidant defense (TEAC), mitochondrial complex IV activity (CCO), and nitric oxide (NO) concentration in the prefrontal cortex and blood were measured. As expected, post-tPBM treatment (both red and infrared groups) exhibited increased sucrose consumption compared to the sham (p < 0.001). The red and infrared presented higher serum TEAC levels than the sham and control groups, but these effects did not reach statistical significance (p = 0.306). In contrast, the red group showed lower peripheral TBARS levels than the sham group (p = 0.0048); such effect was similar to the control non-stress group. The infrared group showed higher NO levels within the hippocampus than the sham group p = 0.0134) and higher prefrontal CCO activity levels than the red group (p = 0.012), which was similar to the control non-stress group. Our study demonstrated that animals treated with tPBM using red (600 nm) or infrared (840 nm) wavelengths exhibited significant improvements in both behavioral and biological parameters in the CMS model. In particular, tPBM may offer therapeutic benefits by ameliorating oxidative stress and enhancing mitochondrial function, thereby presenting a promising alternative for the management of MDD.
Effect of 6-Hydroxydopamine on Iron Metabolism in MO3.13 Oligodendrocytes.
Li X, Du C, Chen Z … +3 more , Qu Y, Xie J, Wang J
Neurochem Res · 2026 Feb · PMID 41721865 · Publisher ↗
Iron accumulation in the substantia nigra is a hallmark of Parkinson's disease (PD), but its cellular drivers remain unclear. Oligodendrocytes, the most iron-rich cells in the brain, have been implicated in PD pathology....
Iron accumulation in the substantia nigra is a hallmark of Parkinson's disease (PD), but its cellular drivers remain unclear. Oligodendrocytes, the most iron-rich cells in the brain, have been implicated in PD pathology. Our previous studies showed that 6-hydroxydopamine (6-OHDA) promotes iron accumulation in neurons and astrocytes by increasing iron influx and decreasing efflux. However, its effects on oligodendrocyte iron metabolism remain unknown. In this study, we examined how 6-OHDA affects iron homeostasis and inflammatory gene expression in MO3.13 oligodendrocytes. Using MTT, calcein-AM fluorescence assays, RT-PCR, and Western blotting, we compared undifferentiated and differentiated cells. In undifferentiated oligodendrocytes, 6-OHDA increased transferrin receptor 1 (TfR1) and iron regulatory protein 1 (IRP1) while reducing ferroportin 1 (FPN1), resulting in enhanced iron uptake and reduced export. In contrast, differentiated cells showed decreased TfR1 and IRP1 and increased FPN1, promoting iron efflux. 6-OHDA also induced stage-specific inflammatory responses. In undifferentiated cells, IL-1β and TNF-α mRNA levels rose in a dose-dependent manner, whereas differentiated cells selectively upregulated IL-1β. These results suggest that undifferentiated oligodendrocytes undergo iron-related inflammation that may promote differentiation, while differentiated cells respond with a more restricted cytokine profile. This study is the first to demonstrate that 6-OHDA promotes iron accumulation in undifferentiated oligodendrocytes by disrupting the IRP1-mediated balance between TfR1 and FPN1. Moreover, 6-OHDA induces distinct inflammatory responses depending on the stage of oligodendrocyte differentiation. These findings highlight the dual role of oligodendrocytes as both iron reservoirs and modulators of the neuroinflammatory microenvironment, providing new insights into the cellular mechanisms underlying nigral iron accumulation in PD, and suggesting that oligodendrocytes play a critical regulatory role in PD pathogenesis.
Ozone Treatment Attenuates Neuroinflammation and Alters miRNA Expression in a Rat Model of Post-Traumatic Epilepsy.
Demir H, Demirtas C, Yildirim H … +9 more , Demir E, Uzun SK, Sevgin K, Beyaztaş H, Güler EM, Hekimoglu G, Coskunpinar EM, Sanlier N, Yildirim M
Neurochem Res · 2026 Feb · PMID 41718951 · Full text
The aim of this study was to investigate the effects of intraperitoneal ozone therapy in a post-traumatic epilepsy (PTE) model. An in vivo PTE model was established in male Sprague-Dawley rats, which were randomised to c...
The aim of this study was to investigate the effects of intraperitoneal ozone therapy in a post-traumatic epilepsy (PTE) model. An in vivo PTE model was established in male Sprague-Dawley rats, which were randomised to control (n = 8), PTE (n = 10), and PTE + Ozone (n = 10) groups. 0.7 mg/kg ozone was administered intraperitoneally for 3 consecutive days. Seizure activity was video recorded for 120 min and evaluated for latency, frequency, duration, and severity. Behavioral assessments of locomotor activity, anxiety, and spatial memory were conducted using open field, elevated plus, and radial arm maze tests on days 4-6 after the first ozone application. Blood and brain tissues were collected for biochemical assays (SUR1, TRPM4, IL-1β, IL-6, TNF-α, TAS, TOS, OSI, thiol-disulfide homeostasis), histological analyses (H&E, Cresyl Violet, and 8-OHdG immunostaining), and qRT-PCR of epilepsy-related miRNAs. Significant differences were observed among the groups for all serum and brain biomarkers (p < 0.001). The PTE group showed marked increases in SUR1, TRPM4, IL-1β, IL-6, TNF-α, TOS, OSI, TT, NT, and DIS levels, accompanied by a decrease in TAS. Ozone treatment partially reversed these changes by reducing cytokine and oxidative stress markers, improving thiol-disulfide balance, and restoring TAS levels. Behavioural testing revealed beneficial effects of ozone, including reduced immobility, fewer errors in the radial arm maze, and increased open-arm exploration. Although seizure severity, latency, and duration were not significantly altered, seizure frequency showed a decreasing trend (p = 0.067). Immunofluorescence for 8-OHdG revealed increased hippocampal oxidative DNA damage in the PTE group, which was attenuated following ozone treatment. Analysis of miRNA expression revealed downregulation in the PTE group, whereas ozone treatment resulted in overall upregulation. There was no statistically significant difference between miRNA expression results and the PTE + Ozone group (p = 0.056-0.076). Ozone therapy mitigated oxidative stress and inflammation, improved redox homeostasis, enhanced cognitive and locomotor performance, and reduced hippocampal DNA damage in the PTE model. Furthermore, the observed upregulation of specific miRNAs following ozone treatment highlights a potential molecular mechanism contributing to its neuroprotective effects.
Neuroprotective Mechanisms of Ficus deltoidea in an Alzheimer's Disease-Like Rat Model: Targeting Tau Hyperphosphorylation Through Glycogen Synthase Kinase-3 Beta and Protein Phosphatase 2A Regulation.
Manoharan SD, Usman AS, Abdul Hamid H … +5 more , Che Mohd Nassir CMN, Cheema MS, Che Ramli MD, Mohd Moklas MA, Mehat MZ
Neurochem Res · 2026 Feb · PMID 41718891 · Full text
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by memory loss, neurodegeneration, amyloid plaque accumulation and tau hyperphosphorylation. Dysregulation of glycogen synthase kinase-3β...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by memory loss, neurodegeneration, amyloid plaque accumulation and tau hyperphosphorylation. Dysregulation of glycogen synthase kinase-3β (GSK-3β) and protein phosphatase 2 A (PP2A) plays a pivotal role in tau pathology, contributing to synaptic dysfunction and memory impairment. Current AD medications offer limited palliative care, underscoring the need for multifaceted therapeutic strategies. Ficus deltoidea (FD), a medicinal plant renowned for its antioxidant and anti-inflammatory properties, has demonstrated neuroprotective effects, however, its specific role in modulating tau-associated proteins in AD remains underexplored. Thus, this study investigated the neuroprotective properties of FD on the spatial learning and memory, hippocampal histology and the levels of GSK-3β and PP2A in an AD-like rat model. Male rats were administered D-galactose (60 mg/kg) and aluminum chloride (200 mg/kg) for 11 weeks to induce AD-like characteristics. Rats were divided into six groups: control, AD model, donepezil-treated (1 mg/kg), and FD-treated groups receiving 50, 100 and 200 mg/kg of FD extract. Behavioural performances were assessed using the open field test (OFT) and modified elevated plus maze (mEPM). FD administration significantly improved spatial learning and memory in AD-like rats. Nissl staining revealed an increase in viable hippocampal granule neurons in FD-treated rats. Immunoblot analysis reported a reduction in GSK-3β and an increase in PP2A levels, suggesting reduced hippocampal tau phosphorylation. These findings indicate that FD confers neuroprotection by restoring the kinase-phosphatase balance, which in turn enhances hippocampal neuronal survival and memory, thereby supporting its potential as a phytotherapeutic agent for AD intervention.
Chaetoglobosin F Attenuates Amyloid-β-Induced Neurotoxicity in Caenorhabditis elegans by Regulating Autophagy and Oxidative Stress Via the Insulin/IGF-1 and p38 MAPK Pathways.
Lu X, Xu K, Zhou Z … +8 more , Ding G, Zhang Y, Liang Y, Zhou J, Jia M, Zhang Y, Shen L, Li H
Neurochem Res · 2026 Feb · PMID 41714576 · Publisher ↗
Alzheimer's disease (AD) is a progressive neurodegenerative disease for which no effective clinical therapies currently exist. The neuroprotective potential of Chaetoglobosin F (CF), a fungal secondary metabolite, was in...
Alzheimer's disease (AD) is a progressive neurodegenerative disease for which no effective clinical therapies currently exist. The neuroprotective potential of Chaetoglobosin F (CF), a fungal secondary metabolite, was investigated in this study using a Caenorhabditis elegans (C. elegans) model of AD that are transgenic nematodes expressing amyloid-beta (Aβ). Key parameters evaluated included paralysis rate, lifespan, motor and cognitive functions, Aβ plaque aggregation, intracellular reactive oxygen species (ROS), and autophagosome formation. The transcriptional levels of genes were examined by real time PCR. Results showed that treatment with CF significantly delayed paralysis, extended lifespan, and ameliorated Aβ-induced deficits in locomotion and chemotaxis. CF markedly reduced Aβ plaque accumulation, suppressed intracellular ROS levels, and promoted autophagosome formation. Furthermore, CF had potent inhibitory effects on acetylcholinesterase (AChE) activity. These beneficial effects were correlated with the upregulation of crucial genes, including daf-16, skn-1, pmk-1, mtl-1, unc-51, bec-1, lgg-1, sod-1 and sod-3, which confirmed the improving antioxidant defenses and autophagy. Our findings demonstrate that CF confers strong neuroprotection against Aβ-induced toxicity in C. elegans by co-regulating oxidative stress and autophagy through the Insulin/IGF-1 (IIS) and p38 MAPK signaling pathways. These results suggest that CF is a promising natural compound for further investigation as a potential therapeutic agent for AD.
The Impact of REM Sleep Deprivation on ER Stress and Alzheimer-Like Pathology: Therapeutic Potential of Melatonin.
Çakır A, Şehzade S, Koç C … +5 more , Çilingir S, Acar D, Süyen G, Bican Demir A, Kahveci N
Neurochem Res · 2026 Feb · PMID 41706263 · Full text
REM sleep deprivation (REMSD) contributes to neurodegenerative diseases like Alzheimer’s Disease (AD). This study examined REMSD’s effects on cognition, ER stress, and AD-like pathology in rats, alongside melatonin’s the...
REM sleep deprivation (REMSD) contributes to neurodegenerative diseases like Alzheimer’s Disease (AD). This study examined REMSD’s effects on cognition, ER stress, and AD-like pathology in rats, alongside melatonin’s therapeutic potential. REMSD was induced for six days using the modified multiple platform method (MMPM). Cognitive function was tested via the Morris Water Maze (MWM). Rats received melatonin (20 mg/kg), 4-PBA (as a positive control, 100 mg/kg), or vehicle during deprivation/recovery periods. Western blotting and ELISA assessed ER stress markers (BiP, pIRE1, pPERK, peIF2-α, CHOP and GRP94, GADD34), Alzheimer related molecules (Aβ40/42, Tau, APP, GSK3β) and apoptosis-related proteins (Caspase 2, Caspase 12, BAX/Bcl-2). In addition, the mRNA expression levels of ATF4 and ATF6 were determined by PCR. Recovery sleep restored cognition, but melatonin/4-PBA enhanced it further. REMSD was associated with increased ER stress and AD-like pathology, whereas melatonin and 4-PBA appeared to attenuate these alterations, possibly by influencing the unfolded protein response (UPR) and reducing protein misfolding. Melatonin shows promise in countering SD-associated neurodegeneration, highlighting sleep’s role in proteostasis and its potential clinical use in AD and protein-misfolding disorders.
Ginsenoside Rb1 Inhibits Phosphorylation of Cx43 and Promotes Mitophagy To Attenuate Mouse Cerebral Ischemia/Reperfusion Injury.
Chen W, Ye G, Chen P … +5 more , Wang H, Li Z, Liu X, Zhang G, Feng J
Neurochem Res · 2026 Feb · PMID 41703332 · Publisher ↗
Cerebral ischemia/reperfusion injury is a leading cause of neurological deficits, with limited treatment options available. Ginsenoside Rb1 (GRb1), a major bioactive compound of Panax ginseng, has shown neuroprotective p...
Cerebral ischemia/reperfusion injury is a leading cause of neurological deficits, with limited treatment options available. Ginsenoside Rb1 (GRb1), a major bioactive compound of Panax ginseng, has shown neuroprotective potential. This study investigates whether GRb1 exerts its protective effects against cerebral ischemia/reperfusion injury, focusing on its effects in promoting mitophagy as the underlying mechanism. Male C57BL/6J mice underwent middle cerebral artery occlusion for 30 min followed by reperfusion. Mice were divided into four groups: Sham, Vehicle, GRb1-treated, and GRb1 combined with Mdivi-1, a mitophagy inhibitor. GRb1 (20 mg/kg) and Mdivi-1 (40 mg/kg) were administered intraperitoneally at 1 h, 12 h, and 24 h post-ischemia, followed by daily injections. Cognitive function and anxiety-like behavior were assessed using the Morris Water Maze and Open Field Test. Neuroinflammation, mitochondrial function, and connexin 43 phosphorylation were analyzed through immunofluorescence, Western blot, and ELISA. Mitophagy was evaluated by examining key markers, including PINK1, Parkin, Atg5, LC3 II, and p62. GRb1 significantly improved cognitive function and reduced anxiety-like behavior following ischemia/reperfusion injury. GRb1-treated mice exhibited decreased microglial activation and reduced levels of pro-inflammatory cytokines IL-1β and TNF-α while increasing the anti-inflammatory cytokine IL-10. Additionally, GRb1 preserved mitochondrial function by enhancing ATP production, increasing superoxide dismutase activity, and upregulating PGC1α while reducing Drp1 expression. Western blot analysis revealed that GRb1 decreased connexin 43 phosphorylation and enhanced mitophagy, as indicated by increased levels of PINK1, Parkin, Atg5, and LC3 II, with reduced p62 accumulation. Importantly, these protective effects were largely diminished when mitophagy was inhibited by Mdivi-1. GRb1 exerts its neuroprotective effects against cerebral ischemia/reperfusion injury through the activation of mitophagy. Targeting mitophagy may represent a promising therapeutic strategy for ischemic stroke and related neurological disorders.
Fascin-1 Limits Secondary Damage by Preventing Oxidative‑Stress‑Induced Microglial Death After Spinal Cord Injury.
Zhan F, Xu D, Shi T … +4 more , Niu H, Wang S, Feng E, Cao Y
Neurochem Res · 2026 Feb · PMID 41701401 · Publisher ↗
Secondary injury after spinal cord injury (SCI) is driven by oxidative stress, microglial activation, and apoptosis. Fascin‑1, an actin‑bundling protein implicated in immune regulation, may influence these processes, but...
Secondary injury after spinal cord injury (SCI) is driven by oxidative stress, microglial activation, and apoptosis. Fascin‑1, an actin‑bundling protein implicated in immune regulation, may influence these processes, but its role in SCI remains unclear. We analyzed a mouse spinal cord single‑nucleus RNA‑seq dataset across five time points after T9 SCI to define cell-type-specific Fascin‑1 dynamics. We modeled oxidative stress in human (HMC3) and mouse (BV2) microglia using HO and assessed the effects of Fascin‑1 overexpression on viability, apoptosis, reactive oxygen species (ROS), redox biomarkers, and apoptosis/antioxidant proteins. In a rat contusion SCI model, we delivered AAV‑Fascin‑1 and evaluated locomotor recovery, histopathology, apoptosis, redox indices, and protein expression. Single‑nucleus analysis reveal that Fscn1 expression transiently decreased in microglia and astrocytes early after SCI, then recovered. In vitro, Fascin‑1 overexpression enhanced microglial viability under HO, reduced apoptosis and ROS, decreased MDA, restored SOD/GPx activity and the GSH/GSSG balance, downregulated Bax and cleaved Caspase‑3/9, and upregulated Bcl-2. In vivo, AAV‑Fascin‑1 improved BBB scores from day 7 to 14 post‑SCI, reduced lesion cavitation and fibrotic scarring, preserved Nissl‑positive neurons, and normalized redox indices and apoptosis/antioxidant protein levels. Fascin‑1 mitigates oxidative stress and apoptosis in microglia and attenuates secondary damage via activation of the NRF2/HO‑1 axis after SCI. These findings identify FSCN1 as a potential therapeutic target to enhance functional recovery following SCI.
Investigating the Neuroprotective Effects of Saw Palmetto Fruit Extract Against D-Galactose and Aluminum Chloride Induced Alzheimer's Disease: In Vivo Study.
Nisar A, Akhter N, Chauhdary Z … +5 more , Anjum F, Saleem F, Sana S, Rafiq I, Mustafa A
Neurochem Res · 2026 Feb · PMID 41701395 · Publisher ↗
Serenoa repens (Saw palmetto) contain 85–90% fatty acids and other constituents include sterols rich in components as carotenoids, lipases, tannin and sugars. The purpose of this study is to investigate the therapeutic p...
Serenoa repens (Saw palmetto) contain 85–90% fatty acids and other constituents include sterols rich in components as carotenoids, lipases, tannin and sugars. The purpose of this study is to investigate the therapeutic potential of Saw palmetto fruit extract against Alzheimer’s disease in a mice model. Phytochemical analysis was performed by HPLC analysis after preparation of plant extract by microwave assisted extraction technique.AD induced in mice by D-galactose and aluminum chloride 100 mg/kg of each (orally), and treated with saw palmetto fruit extract 250 mg/kg, 500 mg/kg, and 800 mg/kg were administered orally for 21 days. Neurobehavioral observations were performed to determine the pharmacological manipulation on cognitive and behavioral functions. Mice were sacrificed after behavioral studies to perform biochemical, neurochemical and gene expression analysis. Neuro-active compounds detected in HPLC analysis like chlorogenic acid, p-coumaric acid, gallic acid, HB acid and salicylic acid were screened by the molecular docking and interaction analysis. SP extract treatment showed dose-dependent neuroprotective effects as manifested by neurobehavioral, histopathological analysis which showed that with 250 mg/kg moderately enhance the synaptic density and neuronal survival. Notable neurodegenerative effects were observed at 800 mg/kg, accompanied by reduced neurodegenerative histopathology at 500 mg/kg. Phytochemicals in SP extract showed most stable conformation within the active site of target protein AChE. ADMET results sustained the computational experiments by presenting significant results, further molecular dynamic analysis also confirms the perfect interaction of the target AChE protein with Quercetin, Chlorogenic acid. These five phytochemicals could be recommended for clinical testing for management of Alzheimer’s disease.
Decorin Attenuates Epileptogenesis and Modulates Hippocampal Synaptic Plasticity via the mTOR Signalling Pathway.
Liu Z, Shen Y, Luo AD … +7 more , Ao WL, Guan SQ, Lei F, Xu ZC, Yu CY, Xu P, Huang H
Neurochem Res · 2026 Feb · PMID 41701388 · Publisher ↗
The pathophysiological mechanism of epilepsy has not been fully elucidated. Abnormal synaptic plasticity in the hippocampus may be an important trigger. Decorin (DCN), an extracellular matrix protein, may affect synaptic...
The pathophysiological mechanism of epilepsy has not been fully elucidated. Abnormal synaptic plasticity in the hippocampus may be an important trigger. Decorin (DCN), an extracellular matrix protein, may affect synaptic remodeling by regulating the mTOR signalling pathway. However, its role and molecular mechanism in epilepsy remain unclear. In this study, a chronic epilepsy mouse model induced by kainic acid (KA) was established. The protein expression of DCN in the hippocampus was significantly increased during the occurrence of epilepsy. By using an adeno-associated virus (AAV) to knock down DCN expression in the hippocampus, the effect of DCN on the occurrence of epilepsy was explored. The experiments revealed that knocking down DCN could significantly shorten the duration of status epilepticus, reduce the frequency and severity of spontaneous seizures, etc. Moreover, DCN knockdown could improve synaptic remodelling by downregulating the expression of key proteins, such as AMPA/NMDA receptor subunits (GluN2A, GluN2B) and PSD95, on the postsynaptic membrane, and reducing the abnormal increase in dendritic spine density and the number of synaptic vesicles. Molecular mechanism studies revealed that DCN physically interacts with mTOR protein, and its knockdown coincided with reduced phosphorylation and activation of mTOR. These findings suggest a potential link between DCN and mTOR signalling. Therefore, the DCN-mTOR axis emerges as a potential target for modulating the excessive synaptic transmission associated with epilepsy. This study is the first to reveal that DCN participates in the pathological process of epilepsy by regulating mTOR-dependent synaptic plasticity, providing experimental evidence that the DCN-mTOR axis can be targeted to intervene in synaptic homeostasis imbalance.
Rotating Magnetic Field Therapy Induces System-Level Neuroprotection in A53T α-Synuclein Transgenic Mice Through Coordinated Suppression of Cellular Stress Pathways.
Anayyat U, Kiani MN, Mei X … +7 more , Zhang F, Fatima A, Yang Z, Li K, Zheng G, Wei Y, Wang X
Neurochem Res · 2026 Feb · PMID 41701385 · Publisher ↗
Current therapeutic strategies for Parkinson's disease (PD) focus exclusively on symptomatic management without addressing underlying disease progression. Despite decades of research emphasizing the enhancement of the ce...
Current therapeutic strategies for Parkinson's disease (PD) focus exclusively on symptomatic management without addressing underlying disease progression. Despite decades of research emphasizing the enhancement of the cellular defense pathway, disease-modifying treatments remain elusive. We evaluated rotating magnetic field (RMF) therapy in A53T transgenic mice harboring a familial PD-associated mutation. Transgenic and wild-type animals (n = 8 per group) received RMF treatment (4 Hz, 0.4 T, 2 h daily) for six months. Motor function, muscle strength, and neuropathological markers were assessed. Comprehensive transcriptomic and proteomic analyses were performed to elucidate the molecular mechanisms involved. Untreated A53T transgenic mice exhibited progressive motor decline (51% reduction in locomotor activity, 39% decrease in muscle strength) accompanied by the accumulation of pathological α-synuclein aggregates. RMF-treated transgenic mice demonstrated significant functional recovery, with 78% wild-type locomotor activity and 80% normal muscle strength, with a marked reduction in α-synuclein pathology. Molecular profiling revealed unexpected suppression of hyperactivated stress response pathways, including mTOR signaling, autophagy, and oxidative stress responses (NES = -2.05 to -2.65, FDR < 0.01), whereas metabolic defense mechanisms such as glutathione biosynthesis were increased (NES = 2.18, FDR < 0.001).These findings suggest that normalization of aberrant stress signaling through RMF therapy represents a novel disease-modifying strategy with potential applicability to other neurodegenerative disorders characterized by proteostasis dysfunction.
Correction: Ciprofol Promotes SIRT1-Mediated Raf Regulation of ERK1/2 Hyperphosphorylation.
Wang J, Lin J, Liu L … +4 more , Liu S, Xie Z, Jiang S, Huang H
Neurochem Res · 2026 Feb · PMID 41670786 · Publisher ↗
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AQP4-IgG-Induced Astrocyte-Derived Small Extracellular Vesicles Carrying Mitochondrial DNA Regulate the TLR9/MyD88/NF-κB Pathway to Drive Microglial Activation and Neuromyelitis Optica.
Zhou J, Li H, Wen Y … +3 more , He L, He Y, Meng H
Neurochem Res · 2026 Feb · PMID 41670763 · Publisher ↗
Neuromyelitis optica spectrum disorder (NMOSD) is a rare but serious inflammatory demyelinating disease. A key characteristic of NMOSD is the presence of a pathogenic autoantibody in serum called aquaporin-4 immunoglobul...
Neuromyelitis optica spectrum disorder (NMOSD) is a rare but serious inflammatory demyelinating disease. A key characteristic of NMOSD is the presence of a pathogenic autoantibody in serum called aquaporin-4 immunoglobulin G (AQP4-IgG). This study investigates the mechanism of astrocyte-derived small extracellular vesicles (EVs) carrying mitochondrial DNA (mtDNA) to promote AQP4-IgG-induced microglial activation in neuromyelitis optica (NMO) via the toll-like receptor 9 (TLR9)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway. Serum IgG was isolated from NMOSD patients (AQP4-IgG) and healthy controls (Con-IgG). Astrocytes were treated with AQP4-IgG or Con-IgG. EVs were isolated via ultracentrifugation, characterized, and examined for internalization. Microglia were exposed to EVs, and mtDNA levels were assessed. An NMO mouse model was established, with neurological damage, mouse behaviors, tissue damage, and microglial characterization evaluated using modified neurological severity score, open-field test, rotarod test, luxol fast blue staining, and flow cytometry. Inflammatory cytokines, TLR9, MyD88, p65, IκBα, p-p65, and p-IκBα in BV2 cells and spinal cord tissues were analyzed via ELISA, RT-qPCR, and western blot. AQP4-IgG-induced astrocyte-derived EVs increased Iba1-high-expressing and CD86/tumor necrosis factor-α-high-expressing cells, reduced CD206/transforming growth factor-β-high-expressing cells, and boosted inflammatory responses. AQP4-IgG-induced EVs carried mtDNA to activate microglia via the TLR9/MyD88/NF-κB pathway. TLR9/MyD88/NF-κB pathway inhibition reversed AQP4-IgG-induced EVs' promotion on microglial activation. In vivo, AQP4-IgG-induced EVs-mtDNA exacerbated microglial activation and NMO through the TLR9/MyD88/NF-κB pathway. AQP4-IgG-induced EVs carried mtDNA to upregulate TLR9, further activating the MyD88/NF-κB pathway, thereby promoting microglial activation and transition toward pro-inflammatory gene-high-expressing cells to drive NMO progression.
Glucocorticoid-Mediated Astrocytic L-Lactate Release Drives Chronic Postsurgical Pain via Spinal Neuronal Sensitization.
Li Y, An Y, Wu Y … +1 more , Wei X
Neurochem Res · 2026 Feb · PMID 41661438 · Publisher ↗
Chronic post-surgical pain (CPSP) in rats is characterized by persistent mechanical allodynia and spinal neuronal hypersensitivity. Astrocyte-derived L-lactate, a key modulator of neuronal excitability and synaptic plast...
Chronic post-surgical pain (CPSP) in rats is characterized by persistent mechanical allodynia and spinal neuronal hypersensitivity. Astrocyte-derived L-lactate, a key modulator of neuronal excitability and synaptic plasticity, was herein investigated for its role in CPSP development following skin/muscle incision and retraction (SMIR). SMIR triggered long-lasting mechanical allodynia, concomitantly with astrocyte activation and elevated L-lactate levels in the spinal dorsal horn. Blockage of glycogenolysis by 4-dideoxy-1,4-imino-D-arabinitol (DAB), inhibition of carbonic anhydrase (CA) by acetazolamide or inhibition of soluble adenylyl cyclase (sAC) by bithionol prevented SMIR-induced mechanical allodynia and reduced spinal dorsal horn L-lactate levels, implicating a critical role of astrocyte-derived lactate in CPSP development and maintenance. Chemogenetic inhibition of spinal astrocyte suppressed mechanical allodynia and decreased L-lactate accumulation in the dorsal horn. Notably, exogenous L-lactate enhanced the firing rate of spinal lamina Ⅰ-II neurons but failed to alter excitatory synaptic transmission, suggesting a selective role for L-lactate in modulating spinal neuronal intrinsic excitability. Mechanistically, SMIR elevated plasma glucocorticoid levels, while adrenalectomy (ADX) abolished both SMIR- induced mechanical allodynia and spinal lactate elevation. Collectively, these findings indicate that glucocorticoid receptor signaling drives astrocytic L-lactate release in spinal dorsal horn following SMIR, which promotes spinal neuronal hyperexcitability and contributes to CPSP pathogenesis.
Integrative Analysis of Trace Elements, Oxidative Stress, and Psychological Distress in Epilepsy: Biochemical Profiling and In Silico Docking Insights.
Vishwakarma S, Pathak A, Maurya AK … +4 more , Singh S, Ashish A, Singh NK, Singh R
Neurochem Res · 2026 Feb · PMID 41661398 · Publisher ↗
Epilepsy is a complex neurological disorder shaped by oxidative stress, imbalances in trace elements, and psychological distress, yet the mechanisms linking these factors to seizure severity and psychiatric outcomes rema...
Epilepsy is a complex neurological disorder shaped by oxidative stress, imbalances in trace elements, and psychological distress, yet the mechanisms linking these factors to seizure severity and psychiatric outcomes remain poorly understood. This study investigated their interplay through clinical, biochemical, and in silico approaches. A cross sectional analysis was conducted on 200 epilepsy patients and 200 controls with comparable age and sex distributions. Psychological distress was measured using the Depression Anxiety Stress Scale-21 (DASS-21). Serum levels of copper (Cu), zinc (Zn), selenium (Se), iron (Fe), chromium (Cr), and magnesium (Mg) were quantified via atomic absorption spectrophotometry, while oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were assessed by ELISA. Hierarchical regression identified predictors of stress and anxiety, and molecular docking was employed to evaluate interactions of Cu, Zn, Se, and MDA with SOD. Results revealed that epilepsy patients had significantly higher stress, anxiety, depression, Cu, and MDA levels, along with reduced Zn, Se, SOD, and GSH. Regression analyses indicated that Cu and MDA were positive predictors of psychological distress, while Zn, Se, and SOD exerted protective effects. Docking studies demonstrated strong binding of Cu and MDA to SOD, potentially impairing its activity, whereas Zn and Se promoted stabilization of antioxidant defenses. These findings suggest that trace element dysregulation and oxidative stress contribute to both seizure pathology and psychiatric comorbidities, reinforcing a cycle of neuronal excitatory imbalance, and psychological vulnerability. Integrating antioxidant based therapies and trace element correction with mental health monitoring may improve personalized management of epilepsy. This study is distinctive in combining clinical, biochemical, psychological, and molecular docking analyses to unravel the synergistic effects of trace elements and oxidative stress on epilepsy outcomes.
Contextual Fear Conditioning Selectively Increases Levels of Arc and c-Fos Proteins in the Dorsal, but not the Ventral Hippocampus.
Kumar Y, Jha SK
Neurochem Res · 2026 Feb · PMID 41661368 · Publisher ↗
The hippocampus plays an important role in contextual fear-conditioning and exhibits functional specialization along its dorso-ventral axis. The dorsal hippocampus (DH) is primarily involved in spatial and contextual pro...
The hippocampus plays an important role in contextual fear-conditioning and exhibits functional specialization along its dorso-ventral axis. The dorsal hippocampus (DH) is primarily involved in spatial and contextual processing, whereas the ventral hippocampus (VH) modulates affective and emotional components of memory. Although these regions are functionally interconnected, their differential neuronal temporal dynamics during contextual fear conditioned (CxFC) memory consolidation and retrieval remain unclear. In this study, we examined the selective engagement and activity-dependent changes during the early phase of CxFC memory consolidation and retrieval in the DH and VH. Mice were subjected to fear-conditioning, and freezing behaviour was assessed during baseline, training, and testing sessions as a measure of fear memory. The levels of Arc and c-Fos proteins in the DH and VH were measured at 0, 1, 3, and 5 h. The freezing response increased significantly during testing compared to the baseline day. The level of Arc and c-Fos proteins significantly increased in the DH but not in the VH during the training and testing days. Arc levels in the DH showed a time-dependent increase, peaking at the 1st hour, and remaining significantly elevated through the 5th hour on conditioning and post-conditioning days, with no corresponding changes observed in the VH. Similarly, c-Fos levels in the DH increased significantly at 1, 3, and 5 hours on both days, with no corresponding changes in the VH. Our results suggest that the DH may play an essential role in mediating the early phase of CxFC memory formation and its subsequent retrieval.
MARCH6 Confers Protection Against Endoplasmic Reticulum Autophagy in Gliomas by Destabilizing FAM134B.
Zhou Y, Chen R, Liu G … +5 more , Zhang L, Zheng H, Zheng J, Zuo X, Xie P
Neurochem Res · 2026 Feb · PMID 41661358 · Publisher ↗
This study probed the mechanism of MARCH6 in endoplasmic reticulum autophagy (ER-phagy) during glioma development by regulating FAM134B stability. MARCH6 and FAM134B expression levels were measured in glioma tissues. A c...
This study probed the mechanism of MARCH6 in endoplasmic reticulum autophagy (ER-phagy) during glioma development by regulating FAM134B stability. MARCH6 and FAM134B expression levels were measured in glioma tissues. A comparative analysis was conducted on the correlation between clinical parameters and FAM134B expression in 46 glioma patients. FAM134B and MARCH6 were knocked down in glioma cells, followed by detection of cell viability and apoptosis, typical ER stress (ERS) markers (PERK, IRE1α, eIF2α, and CHOP), autophagy-related proteins (P62 and LC3B), and autophagosome cytoplasmic accumulation. A mouse glioma model was established for in vivo validation. MARCH6-FAM134B interaction, FAM134B ubiquitination levels, and protein stability were examined. FAM134B expression was high and MARCH6 expression was low in glioma tissues. MARCH6 induced FAM134B protein ubiquitination and degradation, reducing its stability in glioma cells. Knockdown of FAM134B reduced glioma cell survival, inhibited PERK, IRE1α, eIF2α, and CHOP expression, decreased LC3I to LC3II conversion, lowered LC3B fluorescence expression, and reduced the accumulation of autophagosomes with continuous ER structures in the cytoplasm, while enhancing apoptosis and P62 expression. This effect can be reversed by knocking down MARCH6. In vivo, FAM134B knockdown suppressed tumorigenesis in mice. MARCH6 exerts a repressive effect on ERS responses and ER-phagy in glioma cells by destabilizing FAM134B.
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