Neurochem. Res. [JOURNAL]
Sun
200 papers
Serum Aberrant Expression of miR-431-5p and Their Diagnostic Value in Parkinson's Disease.
Liu C, Xu J, Mao S … +3 more , Li P, Lai F, Chen P
Neurochem Res · 2026 Jan · PMID 41549156 · Publisher ↗
Non-coding RNA plays an important role in the occurrence and development of Parkinson's disease (PD). This study only explores the diagnostic value of miR-431-5p in PD and its role in the development of PD. A total of 92...
Non-coding RNA plays an important role in the occurrence and development of Parkinson's disease (PD). This study only explores the diagnostic value of miR-431-5p in PD and its role in the development of PD. A total of 92 patients with PD were selected as the PD group, and 100 healthy individuals undergoing physical examinations were selected as the control group. The levels of serum miR-431-5p were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic value of serum miR-431-5p for PD. Multivariate Logistic regression was utilized to analyze the risk factors of PD with cognitive impairment. The in vitro PD cell model was constructed by inducing SH-SY5Y cells with MPP, and the effects of miR-431-5p on the proliferation, apoptosis, inflammation, oxidative stress and autophagy of the cell model were explored. Luciferase reporter gene was used to evaluate the interaction between miR-431-5p and its downstream target genes. The expression of miR-431-5p in PD is decreased, and its expression in PD with cognitive impairment is lower than that in PD without cognitive impairment. The diagnostic value of miR-431-5p combined with α-Syn for PD is better than that of a single indicator. Logistics regression analysis demonstrated that total unified Parkinson's disease rating scale (UPDRS) and miR-431-5p were the risk factors for the occurrence of PD with cognitive impairment. In vitro studies have shown that MPP induces the inhibition of proliferation and the promotion of apoptosis, autophagy, inflammation and oxidative stress. However, the above effects can be offset by the addition of miR-431-5p mimics. SOX9 is a direct target gene of miR-431-5p, which is upregulated in PD. miR-431-5p is down-regulated in PD and has clinical significance for the early diagnosis of PD. miR-431-5p may play a role in the progression of PD by targeting SOX9.
Retraction Note: Xanthohumol Attenuates Lipopolysaccharide-Induced Depressive Like Behavior in Mice: Involvement of NF-κB/Nrf2 Signaling Pathways.
Rahman SU, Ali T, Hao Q … +6 more , He K, Li W, Ullah N, Zhang Z, Jiang Y, Li S
Neurochem Res · 2026 Jan · PMID 41549154 · Publisher ↗
Abstract loading — click title to view on PubMed.
Probiotic Supplementation Modulates FGFR2 and TLR4 Signaling and Attenuates Chronic Neuroinflammation in an Experimental Stroke Model.
Bayat R, Rezvani Z, Rahmatipour S … +2 more , Azami Tameh A, Vahidinia Z
Neurochem Res · 2026 Jan · PMID 41533236 · Publisher ↗
Stroke is a major cause of mortality and morbidity. It is known to induce gut dysbiosis, which can exacerbate brain injury by increasing systemic inflammation and disrupting the gut-brain axis. This study investigated th...
Stroke is a major cause of mortality and morbidity. It is known to induce gut dysbiosis, which can exacerbate brain injury by increasing systemic inflammation and disrupting the gut-brain axis. This study investigated the effects of probiotics on immunomodulation and brain regeneration in a post-stroke animal model, with a particular focus on gut-brain axis. In this study, Male Wistar rats were divided into three groups: Sham, Ischemia and Ischemia + Probiotic. Focal cerebral ischemia was induced by one-hour middle cerebral artery occlusion (MCAO). The probiotic group received 10 CFU/ml probiotic solution via gavage for 14 days. After 14 days, behavioral outcomes and cerebral infarct volume were assessed. Molecular docking was performed to analyze the binding affinities of probiotic metabolites with TLR4 and FGFR2 which were further validated by RT-PCR gene expression analysis. Serum matrix metalloproteinase-9 activity was evaluated using zymography and oxidative stress was assessed by measuring malondialdehyde, total antioxidant capacity, and nitric oxide levels in the ischemic penumbra. According to the results, the probiotic group showed a significant reduction in infarct volume and improved behavioral deficits. Molecular analysis revealed that probiotics increased nitric oxide levels and total antioxidant capacity while decreasing malondialdehyde levels. Consistent with molecular docking, there was a significant increase in FGFR2 and TLR4 gene expression and matrix metalloproteinase-9 activity. These findings show probiotic supplementation reduces brain damage after stroke, likely via the modulation of FGFR2/TLR4 inflammatory pathway, which could originate from gut microenvironment dysregulation.
The Anti-proliferative Effects of Anandamide and Oleamide in Glioblastoma Cell Lines Recruit Mitochondrial and PPAR-γ Receptor Modulation.
Torres-Román AL, Ortega-Gómez A, Reyes-Soto CY … +12 more , Aparicio-Trejo OE, Cuevas-López B, García-Arroyo FE, Ruíz-García E, Matus-Santos JA, Ferrer B, Aschner M, Jardón G, López-Goerne T, Molina-Hernández A, Tenorio-Monterrubio JC, Santamaría A
Neurochem Res · 2026 Jan · PMID 41533230 · Full text
The endocannabinoid anandamide (AEA) and the related metabolite oleamide (ODA) have been demonstrated to possess anti-proliferative properties by recruiting apoptotic mechanisms in glioblastoma cells; however, the role o...
The endocannabinoid anandamide (AEA) and the related metabolite oleamide (ODA) have been demonstrated to possess anti-proliferative properties by recruiting apoptotic mechanisms in glioblastoma cells; however, the role of receptors other than the canonical cannabinoid receptors in their pattern of anti-proliferative mechanisms has been poorly investigated. Here, we evaluated the role of mitochondrial function and PPAR-γ membrane receptors in the anti-proliferative mechanisms induced by AEA and ODA in the glioblastoma cell lines C6 and RG2. Cell viability and lipid peroxidation assessments in both cell lines showed antiproliferative and pro-oxidant effects of the tested cannabinoids, respectively, compared to primary astrocyte cultures used as a non-tumor negative control. AEA and ODA also reduced mitochondrial membrane potential in C6, but not in RG2 cells, while impairing mitochondrial Complex I activity in C6. The PPAR-γ receptor antagonist GW9662 showed differential effects on the AEA- and ODA-induced loss of cell viability in both cell lines, as well as in mitochondrial membrane potential. The ontogenetic origin and metabolic differences between RG2 and C6 cell lines may establish differential responses evoked by endogenous cannabinoids and PPAR-γ receptor modulation. Combined, our results demonstrate that AEA and ODA modulate mitochondrial function in glioblastoma cells by inhibiting the activity of mitochondrial Complex 1, which in turn increases markers of oxidative damage and interferes with glioblastoma proliferation.
The Molecular Signature of Astrocyte Response to Hypoxia Outlines the Metabolic and Cell Survival Mechanisms for Neuroprotection.
Stefanelli R, Spada C, Palma A … +2 more , Canterini S, Fiorenza MT
Neurochem Res · 2026 Jan · PMID 41533048 · Publisher ↗
The molecular reprogramming of astrocyte gene expression induced by oxygen deprivation is one of the astrocyte-mediated neuroprotective processes relevant to neurodegenerative diseases and various brain injury conditions...
The molecular reprogramming of astrocyte gene expression induced by oxygen deprivation is one of the astrocyte-mediated neuroprotective processes relevant to neurodegenerative diseases and various brain injury conditions. The primary oxygen sensor that mediates eukaryotic cells' adaptive response to changes in oxygen concentration is hypoxia-inducible transcription factor 1 alpha (HIF-1α). Therefore, the astrocyte neuroprotective ability triggered by the activation of HIF-1α downstream effectors has sparked interest in hypoxia mimetics-based treatment approaches as a means to induce adaptive responses without direct hypoxia exposure. Compared to similar studies that evaluated the effect of both oxygen and glucose deprivation for several hours, this study uncovers the reprogramming of astrocyte gene expression patterns after exposure to hypoxia alone for short and relatively long periods of time - 30 min for short-term (ST) and three hours for long-term (LT) hypoxia - as well as following 24 h of reoxygenation induced recovery (RIR). The transcriptional activation of a number of genes, including Pdk1, Mct4, Sirt1, Bcl2, Hsp70, and Sod2, ends rather rapidly, only lasting over the ST-hypoxia. Conversely, during LT-hypoxia, Glut1 and Vegf1 show elevated expression, which is likely due to a positive feedback loop in which secreted Vegf increases both its own and Glut1's expression. Interestingly, the ST-hypoxia establishes long-lasting variations of gene expression that may be essential for generating an effective neuroprotective response. This is demonstrated by the fact that Mct4 expression continues to be raised during the 24-hour normoxia period that follows the ST-hypoxia, thereby aiding in metabolic adaptation. Therefore, it is reasonable to draw the conclusion that the length of transcriptional activation varies depending on the gene and is associated with the function of the encoded protein.
Effect of Ang II Receptor Inhibition on GSK-3β/CREB/BDNF Signalling in REM Sleep Deprivation-Induced Memory Impairment.
Elma N, Sayan Özaçmak H, Turan İ
Neurochem Res · 2026 Jan · PMID 41533036 · Full text
REM (rapid eye movement) sleep deprivation causes serious impairments in hippocampus-dependent learning and memory. This study examined whether the angiotensin II receptor blocker telmisartan, given at two different dose...
REM (rapid eye movement) sleep deprivation causes serious impairments in hippocampus-dependent learning and memory. This study examined whether the angiotensin II receptor blocker telmisartan, given at two different doses, could reduce cognitive deficits and affect molecular pathways related to chronic REM sleep deprivation. Thirty-two male Wistar-Albino rats (200-280 g, 3 months old) were randomly divided into four groups (n = 8): control, sleep deprivation (SD), telmisartan-treated SD groups at 1 mg/kg (SD+Tel1) and 3 mg/kg (SD+Tel3). Chronic REM sleep deprivation was induced for 21 days using the modified multiple platform (MMP) method. Telmisartan or distilled water was administered orally once daily. Cognitive performance was tested in the Morris water maze, assessing escape latency and time spent in the target quadrant. After behavioral tests, hippocampal and prefrontal cortex samples were analyzed for brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), glycogen synthase kinase-3 beta (GSK-3β), monocarboxylate transporter 2 (MCT2), and lactate dehydrogenase (LDH) levels, while plasma samples were analyzed for corticosterone (CORT) levels. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitrate, and glycogen were also measured. Sleep-deprived rats showed impaired learning and memory with longer escape latency and reduced time spent of target quadrant. Telmisartan-treated SD groups demonstrated significantly improved cognitive performance, increased BDNF and CREB expression, decreased GSK-3β levels, and balanced oxidative stress markers. In conclusion, telmisartan protected against cognitive and biochemical damage caused by chronic REM sleep deprivation, likely through modulation of GSK-3β/CREB/BDNF signaling and reduction of oxidative stress.
Modulating miRNA-367-3p Expression by Kaempferol Alleviates Experimental Autoimmune Encephalomyelitis: Targeting Fpn1-Dependent Ferroptosis and cAMP/CREB/CNTF Signaling.
El-Gohary RM, Shoeib HM, Barhoma RAE … +8 more , Badr SM, Zaher SM, El Gheit REA, Elshora OA, Elamly MH, Magar MR, Abdelkader GE, Mohamed AS
Neurochem Res · 2026 Jan · PMID 41533024 · Full text
Multiple sclerosis (MS) is a progressive, immune-mediated demyelinating disorder of the central nervous system (CNS). Kaempferol (KAM), a dietary bioflavonoid found in many edible and medicinal plants, exhibits significa...
Multiple sclerosis (MS) is a progressive, immune-mediated demyelinating disorder of the central nervous system (CNS). Kaempferol (KAM), a dietary bioflavonoid found in many edible and medicinal plants, exhibits significant neuroprotective effects in various immunological and neurological disorders; however, its therapeutic potential in MS remains largely unexplored. This study aimed to investigate the protective effects of KAM and the underlying molecular mechanisms using an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. 40 female C57B1/6 mice were assigned to 4 groups: Normal control [saline (i.d.) + DMSO (i.p.)]; KAM [saline (i.d.) + KAM (50 mg/kg/d, i.p.)]; EAE [MOG35–55 immunization (i.d.) + DMSO (i.p.)]; and EAE + KAM [MOG35–55 immunization (i.d.) + KAM (50 mg/kg/d, i.p.)]. The brain and spinal cord were dissected for biochemical, molecular, histopathological, electron microscopic, and immunohistochemical analysis. KAM administration efficiently reduced clinical scores and ameliorated neural cytomorphological abnormalities. KAM profoundly combated iron overload and effectively upregulated ferroportin1 (Fpn1)-encoding gene expression. Furthermore, KAM valuably counteracted neuronal ferroptosis chiefly by restoring the Slc7A11/GSH/GPX4 axis. KAM considerably attenuated proinflammatory cytokine IL-17 and chemokine CCL-19. Intriguingly, KAM promoted axonal remyelination as indicated by an observable escalation in myelin basic protein content through activating the cAMP/CREB/ciliary neurotrophic factor (CNTF) axis. Collectively, for the first time, these findings demonstrated KAM’s neuroprotective potency against EAE, considering its antioxidant, anti-ferroptotic, immunomodulatory, anti-inflammatory, and neurotrophic properties, primarily mediated by inhibiting Fpn1-mediated ferroptosis, activating the cAMP/CREB/CNTF axis, and enhancing miRNA-367-3p expression. Accordingly, miRNA-367-3p has been proposed as an upcoming therapeutic target for MS, and KAM could be a promising treatment option for MS patients.
Ginsenoside Rb1 Maintains Tunneling Nanotubes between Astrocytes and Neurons To Protect Mice from Cerebral ischemia/reperfusion Injury.
Chen W, Feng J, Chen P … +6 more , Wang H, Li Z, Yan J, Ye G, Zhang G, Qin Y
Neurochem Res · 2026 Jan · PMID 41528388 · Publisher ↗
Ginsenoside Rb1 (GRb1), the major bioactive component of ginseng, exhibits multiple therapeutic effects. However, its neuroprotective role in cerebral ischemia/reperfusion (I/R) injury remains unclear. The neuroprotectiv...
Ginsenoside Rb1 (GRb1), the major bioactive component of ginseng, exhibits multiple therapeutic effects. However, its neuroprotective role in cerebral ischemia/reperfusion (I/R) injury remains unclear. The neuroprotective effects of GRb1 were investigated using a mouse middle cerebral artery occlusion (MCAO) model and in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) models. GRb1 was administered intraperitoneally to MCAO mice, and the effects on neurological function, brain edema, blood-brain barrier (BBB) integrity, and extracellular matrix (ECM) remodeling were evaluated. In the OGD/R model, tunneling nanotubes (TnTs) formation, oxidative stress, and mitochondrial integrity were evaluated in a co-culture of astrocytes and neurons. GRb1 markedly enhanced neurological function, alleviated brain edema, and maintained BBB integrity in MCAO mice. It also inhibited the expression of matrix metalloproteinases and Granzyme B while increasing Serpina3n, indicating protection of ECM integrity. In OGD/R-treated neurons, GRb1 reduced oxidative stress, restored superoxide dismutase activity, and preserved ATP and mitochondrial DNA. Importantly, GRb1 significantly enhanced TnTs formation, and inhibition of TnTs with cytochalasin B markedly reversed these protective effects, supporting a TnT-dependent mechanism. GRb1 effectively protected against I/R-induced neuronal injury through TnTs-dependent mechanisms, modulating oxidative stress, ECM remodeling, and mitochondrial integrity.
Exploring Exercise-Linked Neurovascular Unit Adaptations and Sema3G Pathway Involvement in Rats with Vascular Cognitive Impairment.
Dong J, Huang J, Gao F … +4 more , Liu Y, Sun R, Li G, Sui M
Neurochem Res · 2026 Jan · PMID 41504904 · Publisher ↗
Vascular cognitive impairment (VCI) is a neurological disorder in which chronic cerebral hypoperfusion is one of the common causes, often leading to cognitive and motor dysfunction. Moderate-intensity exercise is a non-p...
Vascular cognitive impairment (VCI) is a neurological disorder in which chronic cerebral hypoperfusion is one of the common causes, often leading to cognitive and motor dysfunction. Moderate-intensity exercise is a non-pharmacological intervention that promotes long-term, sustainable, and low-risk brain health restoration. However, the multidimensional functional effects and underlying mechanisms of such training remain insufficiently understood. This study aimed to explore how moderate-intensity training relates to improvements in cognitive and gait functions in VCI, with a focus on neurovascular unit (NVU)-related processes and the potential involvement of vasculogenic Sema3G signaling within the hippocampus. Male Sprague-Dawley rats underwent bilateral common carotid artery occlusion (BCAO) surgery to induce VCI, followed by four weeks of moderate-intensity treadmill training in the exercise group. Moderate-intensity training effectively improved memory performance and gait stability in VCI rats. Exercise also corresponded with increased hippocampal Sema3G expression and higher levels of its related intercellular signaling components (Nrp2/PlexinA4). At the neuronal level, exercise was associated with enhanced synaptic marker expression and elevated hippocampal neuronal firing. In terms of immune modulation, exercise shifted microglial phenotypes toward an anti-inflammatory profile, suggesting a more supportive environment for neurovascular repair. Collectively, these findings indicate that moderate-intensity training may influence multiple NVU components, and that the Sema3G/Nrp2/PlexinA4 signaling axis could be one pathway contributing to the observed cognitive and motor benefits in VCI rats. Moderate-intensity exercise may therefore represent a promising approach for mitigating cognitive and motor decline associated with cerebral hypoperfusion.
Primary Human Reactive Microglia Display Mitochondrial Dysfunction and Metabolic Imbalance Upon Lipopolysaccharide Exposure.
Fontes G, de Sá Hayashide L, Messor DF … +9 more , Marques M, Leocadio VE, Amorim P, Minho AS, Paiva-Pereira E, Savio LEB, Fernandes PD, Pinto RS, Diniz LP
Neurochem Res · 2026 Jan · PMID 41499046 · Publisher ↗
Microglial activation is a central component of neuroinflammation and contributes to the progression of neurodegenerative diseases. However, most of our current understanding is derived from rodent models, which do not f...
Microglial activation is a central component of neuroinflammation and contributes to the progression of neurodegenerative diseases. However, most of our current understanding is derived from rodent models, which do not fully recapitulate human-specific responses. In this study, we employed a human primary microglial model isolated from astrocyte-enriched cultures to investigate the cellular and metabolic alterations induced by inflammatory stimulation with lipopolysaccharide (LPS). The isolated human microglia were characterized by strong expression of canonical markers, including IBA-1, CD68, CD45, F4/80, and TMEM119. Upon LPS exposure, cells displayed a robust reactive phenotype with increased expression of activation markers and NF-κB. Functional validation showed preserved phagocytic activity, confirming the immunocompetent status of the cells. Importantly, this is the first study to demonstrate that human primary reactive microglia exhibit mitochondrial dysfunction in response to inflammatory stimuli. LPS treatment led to a significant reduction in mitochondrial mass (TOMM20), increase in mitochondria fragmentation. We observed that LPS increases the phosphorylation of DRP1, indicating enhanced mitochondrial fission and reduction in mitochondrial membrane potential (TMRE), accompanied by increased production of mitochondrial superoxide (MitoSOX), elevated levels of hydrogen peroxide and nitric oxide. This effect was temporally associated with a decrease in intracellular ATP levels, followed by an increase in extracellular lactate production, suggesting a compensatory glycolytic shift in response to mitochondrial bioenergetic failure. Together, these findings highlight a previously uncharacterized vulnerability of human microglia to inflammatory mitochondrial stress and establish a robust and physiologically relevant platform for studying human-specific mechanisms of microglial activation and bioenergetic failure in neurodegenerative conditions.
Obesity Aggravates Status Epilepticus Through Lipocalin-2-mediated Inflammation and Necroptosis.
Lee GS, Lee SB, Kim MH … +3 more , Roh GS, Kim MJ, Kim HJ
Neurochem Res · 2026 Jan · PMID 41499026 · Publisher ↗
Obesity is an escalating global health concern associated with numerous comorbidities, including an elevated risk of neurodegenerative disorders. Status epilepticus, characterized by prolonged and recurrent seizures, lea...
Obesity is an escalating global health concern associated with numerous comorbidities, including an elevated risk of neurodegenerative disorders. Status epilepticus, characterized by prolonged and recurrent seizures, leads to neuroinflammation and progressive neuronal cell death. Although obesity is recognized as a comorbidity in epilepsy, its mechanistic contribution to SE pathology remains poorly defined. This study investigated the effects of obesity on SE using leptin-deficient ob/ob mice, a well-established model of metabolic dysfunction. Pilocarpine was used to induce SE, and seizure progression was assessed. Compared to wild-type controls, ob/ob mice exhibited significantly reduced latency to seizure onset and a more rapid progression to SE. Fluoro-Jade B staining revealed markedly increased neuronal death in the CA1 and hilus regions of the hippocampus in ob/ob mice. Concurrently, immunofluorescence staining and western blot analysis showed robust astrocyte activation, evidenced by upregulated glial fibrillary acidic protein (GFAP). Obesity also intensified neuroinflammatory signaling, as evidenced by increased levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), along with increased expression of lipocalin-2 (LCN2) and phosphorylated signal transducer and activator of transcription 3(p-STAT3). Furthermore, necroptosis, a regulated form of cell death mediated by mixed lineage kinase domain-like protein (MLKL), was significantly enhanced in ob/ob mice following SE, as indicated by elevated phosphorylated MLKL (p-MLKL) expression. These results suggest that obesity exacerbated seizure susceptibility and amplifies neuroinflammatory and neurodegenerative processes in SE. This work highlights the LCN2-STAT3-MLKL signaling axis as a potential therapeutic target in obesity-associated seizure disorders and offers new insight into the interplay between systemic metabolism and epileptic brain injury.
Altered Fibronectin-α5β1 Integrin-Src Signalling Pathway Drives Network Hyperexcitability in the Hippocampal Formation and Anterior Temporal Lobe in Temporal Lobe Epilepsy.
Yadav N, Priya, Dixit N … +9 more , Anand S, Banerjee J, Tripathi M, Chandra PS, Doddamani R, Sharma MC, Lalwani S, Siraj F, Dixit AB
Neurochem Res · 2026 Jan · PMID 41499010 · Publisher ↗
Fibronectin (FN1), a vital extracellular matrix protein, has been reported to be elevated in blood and cerebrospinal fluid in epileptic patients exhibiting recent seizure activity. A transcriptomic study from MTLE-HS pat...
Fibronectin (FN1), a vital extracellular matrix protein, has been reported to be elevated in blood and cerebrospinal fluid in epileptic patients exhibiting recent seizure activity. A transcriptomic study from MTLE-HS patients has identified FN1 as a potential gene linked to MTLE. Nonetheless, the function of FN1 and the participation of the FN1/α5β1-Integrin/Src kinase signaling pathway are yet to be fully investigated in both pre-clinical and clinical investigations of TLE. Furthermore, its role in NMDA receptor-mediated hyperexcitability in TLE requires investigation. This study evaluates the contribution of the FN1/α5β1-Integrin/Src kinase axis in facilitating NMDA-induced hyperexcitability in temporal lobe epilepsy. Hippocampal formation and ATL tissues from MTLE-HS patients, as well as acute and chronic Li-pilocarpine TLE rat models, were examined using qRT-PCR, immunoblotting, and ex vivo immunolabeling to evaluate the expression of FN1, α5β1 Integrin, Src kinase, and NMDA receptor subunits. To assess the functions of FN1 and Src in NMDA receptor-induced hyperexcitability, siRNA-mediated knockdown was conducted in TLE rats. Following knockdown, behavioral assessments, molecular studies, and in vivo EEG were employed to examine the FN1/α5β1 Integrin/Src axis in seizure-related hyperexcitability.In MTLE-HS patients and TLE rat models, FN1 and Src kinase showed upregulation in both the hippocampal formation and ATL, together with increased α5β1 Integrin levels in rats. Elevated Src activity was associated with augmented phosphorylation of NMDA receptors. The siRNA-mediated knockdown of FN1 or Src diminished NMDA receptor phosphorylation and markedly reduced seizure activity in TLE animals. Our research suggests that FN1 has a role in MTLE pathophysiology and may regulate NMDAR-mediated hyperexcitability via the FN1/α5β1 Integrin/Src kinase pathway. This pathway regulates seizures via the hippocampal formation and anterior temporal lobe networks. The therapeutic potential of targeting this signaling pathway for epilepsy needs additional investigation.
Neuroprotective Effects of C-Phycocyanin in Chronic Unpredictable Mild Stress-Exposed Rats: Regulation of Neuroinflammation and CREB/BDNF Signaling.
Talebi Taheri A, Dadgostar E, Ferdosi F … +7 more , Rahmati-Dehkordi F, Karimi Z, Aschner M, Zahedi E, Mirzaei H, Nabavizadeh F, Tamtaji OR
Neurochem Res · 2026 Jan · PMID 41499003 · Publisher ↗
Depression is a widespread neuropsychiatric disorder that significantly impacts emotional and cognitive function. Antidepressant medications are frequently accompanied by various adverse effects. C-phycocyanin has been p...
Depression is a widespread neuropsychiatric disorder that significantly impacts emotional and cognitive function. Antidepressant medications are frequently accompanied by various adverse effects. C-phycocyanin has been previously shown to exert potent anti-inflammatory, and neuroprotective properties. Therefore, this study evaluated the therapeutic effects of C-phycocyanin against anxiety and depressive-like behaviors, and memory dysfunction in an animal model of chronic unpredictable mild stress (CUMS)-induced depression and explored the underlying mechanisms. Rats were daily exposed for six weeks to CUMS, during which phycocyanin (100 mg/kg, orally) was administered in the final three weeks of the study. Following the assessment of anxiety/ depressive-like behaviors, and memory dysfunction by the open field test (OFT), tail suspension test (TST), elevated plus maze (EPM), and passive avoidance test (PAT), rats were euthanized by decapitation. Then, hippocampal TNF-α and IL-1β concentrations, and hippocampal protein expressions (Iba-1, CD86, NF-κβ, CREB, and BDNF) were determined by an ELISA assay, and western blots, respectively. C-phycocyanin significantly decreased immobility time in OFT and TST, increased open arm time in EPM, and step-through latency time in PAT. Furthermore, C-phycocyanin suppressed CUMS-induced the M1 microglia polarization and neuroinflammation by reducing hippocampal TNF-α and IL-1β concentrations, and the protein expression of Iba-1, CD86, and NF-κβ in the hippocampus of CUMS-exposed rats. It also increased the hippocampal protein expression of CREB and BDNF. C-phycocyanin improved CUMS-induced anxiety and depressive-like behaviors, and memory dysfunction, which could be explained, at least in part, by inhibition of M1 microglial polarization and neuroinflammation, and enhancement of CREB/BDNF signaling.
Deep Brain Stimulation of Lateral Habenula Ameliorates Depression-like Symptoms in Rats: Involvement of Mesolimbic Circuit.
Kanhere HS, Kokare DM, Jogdand YR … +2 more , Dudhabhate BB, Subhedar NK
Neurochem Res · 2026 Jan · PMID 41498987 · Publisher ↗
Deep brain stimulation (DBS) is a promising approach for the treatment of psychiatric disorders including depression, and various targets have been tested for their usefulness. Among these lateral habenula (LHb), a criti...
Deep brain stimulation (DBS) is a promising approach for the treatment of psychiatric disorders including depression, and various targets have been tested for their usefulness. Among these lateral habenula (LHb), a critical site linked to depression, has attracted considerable attention in recent years. DBS at LHb produced antidepressant activity by modulating the monoamine levels. However, the precise circuitry that mediates the positive effects have not been clarified. Herein we employed chronic unpredictable mild stress (CUMS) protocol to generate rats with depression-like phenotype. These animals showed (a) reduced sucrose intake and locomotion, (b) increased immobility in forced swim test, (c) reduction in GAD67 mRNA and increase in VGLUT2 mRNA in the LHb tissue, (d) an increase in glutamate and GABA level in the ventral tegmental area (VTA), and (e) reduction in dopamine in the microdialysates collected from nucleus accumbens shell (AcbSh). Application of DBS, targeted unilaterally at the LHb for 1 h each day for 14 days, resulted in reversal of almost all the above parameters suggesting anti-depressive like action. With a view to dissect the role of GABA in LHb, bicuculline (GABA-A receptor antagonist), administered intra-LHb to CUMS rats, reduced sucrose preference in spite of the application of DBS. We suggest that DBS at LHb may (a) upregulate GABAergic system in LHb, (b) reduce the control exercised by the LHb over VTA via glutamatergic system, and (c) upregulate VTA-Acb pathway. The series of changes finally leading to the increase in DA in Acb, may lead to anti-depressive action.
UNC5B Promotes Post-Stroke Microglial Pyroptosis via DAPK3/MVK Pathway.
Luo Y, Liao S, Yao M … +2 more , Wang R, Yu J
Neurochem Res · 2026 Jan · PMID 41498970 · Publisher ↗
Pyroptotic inflammation has been shown to contribute to neuronal injury after stroke. Uncoordinated-5 homolog B (UNC5B) is implicated in neuroinflammation, and its downstream kinase death-associated protein kinase 3 (DAP...
Pyroptotic inflammation has been shown to contribute to neuronal injury after stroke. Uncoordinated-5 homolog B (UNC5B) is implicated in neuroinflammation, and its downstream kinase death-associated protein kinase 3 (DAPK3) is predicted to interact with mevalonate kinase (MVK). To examine the role of UNC5B in post-stroke pyroptosis, we used a photothrombosis (PT) stroke model in mice and an oxygen-glucose deprivation (OGD) model in BV-2 microglia. Knockdown of Unc5b or Mvk and pharmacological inhibition of DAPK3 were performed, followed by detection of pyroptosis-associated proteins and cell viability. Interactions between DAPK3 and MVK were assessed using transwell coculture and co-immunoprecipitation. PT or OGD induced neuronal injury and increased expression of pyroptosis-related proteins. Knockdown of Unc5b or Mvk in microglia protected neurons by suppressing pyroptosis and disrupting the DAPK3-MVK protein complex. Upregulation of p-MVK was prevented by either Unc5b knockdown or DAPK3 inhibition, whereas DAPK3 upregulation was blocked only by Unc5b knockdown and not by Mvk knockdown. Our results suggest that UNC5B promotes post-stroke microglial pyroptosis in part through the DAPK3/MVK pathway.
Targeting the YY1/HDAC2 Transcriptional Axis by Neferine Ameliorates Sleep Deprivation-Induced Cognitive Deficits.
Li J, Liu Y, Liao Z … +5 more , Zeng C, Zeng L, Han J, Wu Y, Shen Z
Neurochem Res · 2026 Jan · PMID 41498882 · Publisher ↗
Epigenetic dysregulation, particularly through histone acetylation dynamics, is critically implicated in sleep deprivation-induced cognitive dysfunction pathogenesis. This study delineates a novel regulatory axis wherein...
Epigenetic dysregulation, particularly through histone acetylation dynamics, is critically implicated in sleep deprivation-induced cognitive dysfunction pathogenesis. This study delineates a novel regulatory axis wherein histone deacetylase 2 (HDAC2) deficiency mitigates cognitive deficits, while its upstream transcriptional control mechanisms remain poorly characterized. Through integrative bioinformatics and functional genomics, we identified Yin Yang 1 (YY1) as a direct transcriptional activator of HDAC2. Mechanistic investigations revealed YY1 binds the HDAC2 promoter, enhancing its transcriptional activity. Prefrontal cortical YY1 knockdown in murine models precipitated molecular and neurocognitive improvement, including HDAC2 downregulation, elevated expression of synaptic markers, alongside elevated dendritic spine complexity. These findings position YY1 as a sleep deprivation-responsive epigenetic modulator with intrinsic neuroprotective functionality. Translating these mechanistic insights, we conducted pharmacological screening to identify YY1-reducing therapeutics. Neferine (NEF) emerged as a lead compound, demonstrating dual inhibition of the YY1/HDAC2 axis. In chronic sleep deprivation models, NEF administration rescued synaptic deficits and ameliorated cognitive impairments. Crucially, NEF’s neuroprotective efficacy proved entirely contingent upon intact YY1/HDAC2 signaling, as evidenced by its null effects in HDAC2 conditional knockout models. This study reveals YY1 as a key regulator of HDAC2, identifying the YY1/HDAC2 pathway as a potential therapeutic target for sleep deprivation-induced cognitive deficits.
Protective Effects of TNF-α Neutralizing Antibody on the Neurovascular Unit Through Down-Regulating Calpain/NF-κB Inflammatory Pathway During Ischemic Stroke.
Jin C, Wang C, Zhao Y … +2 more , Wang B, Sun M
Neurochem Res · 2026 Jan · PMID 41498875 · Publisher ↗
Tumor necrosis factor-alpha (TNF-α) plays a detrimental role in the brain during ischemic stroke, and TNF-α inhibition has been reported to reduce ischemic brain injury. This study aimed to investigate whether TNF-α cont...
Tumor necrosis factor-alpha (TNF-α) plays a detrimental role in the brain during ischemic stroke, and TNF-α inhibition has been reported to reduce ischemic brain injury. This study aimed to investigate whether TNF-α contributes to neurovascular unit (NVU) damage by modulating the calpain/NF-κB inflammatory pathway following ischemic stroke. Rats were subjected to 1.5 h of transient middle cerebral artery occlusion (MCAO) followed by reperfusion. A TNF-α neutralizing antibody (TNF-α Ab) was administered intracerebroventricularly 15 min before MCAO. The activation of calpain and NF-κB signaling, as well as NVU damage, was evaluated 24 h after MCAO. TNF-α Ab dose-dependently improved neurological function and reduced infarct volumes 24 h post-MCAO. It also attenuated apoptotic cell death, preserved the ultrastructural morphology of the NVU, and decreased blood-brain barrier permeability in the penumbra and core. Moreover, TNF-α Ab increased calpastatin levels, reduced the levels of calpain 1 and calpain 2, and suppressed calpain activity in the cytosol of both the penumbra and core. Additionally, it lowered the cytosolic levels of high mobility group box-1 and elevated cytosolic IκBα levels. TNF-α Ab also reduced cytosolic and nuclear NF-κB p65 levels. Furthermore, it down-regulated the levels of intracellular adhesion molecule-1, interleukin-1β, matrix metalloproteinase (MMP)-2, and MMP-9, and suppressed myeloperoxidase activity in the penumbra and core. These findings demonstrate the protective effects of TNF-α Ab against NVU damage in the ischemic penumbra and core, and suggest that TNF-α contributes to NVU damage by upregulating the calpain/NF-κB inflammatory pathway during ischemic stroke.
Targeting Oxidative Stress and Apoptosis with Levothyroxine in Experimental Parkinson's Disease in Rats.
Houshmand F, Anjomshoa M, Najafi-Chaleshtori S … +4 more , Mobini GR, Zafarian R, Heidari M, Azizi F
Neurochem Res · 2026 Jan · PMID 41498849 · Publisher ↗
Parkinson’s disease is a long-term, progressive condition that affects both movement and other parts of life that aren’t motor-related. Cognitive decline is one of the most impactful non-motor symptoms, as it can serious...
Parkinson’s disease is a long-term, progressive condition that affects both movement and other parts of life that aren’t motor-related. Cognitive decline is one of the most impactful non-motor symptoms, as it can seriously affect overall quality of life. Although existing dopamine replacement therapies, including levodopa, mainly focus on alleviating motor symptoms, they do not adequately address issues such as dyskinesia, non-motor deficits, and the need for neuroprotective treatments. This research aimed to explore the neuroprotective properties of levothyroxine (L-T4) in a PD animal model. Female Wistar rats received 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB) and were treated with L-T4 (10–100 µg/kg) for 3 weeks. The Morris water maze (MWM), rotarod test, rotational behavior, and analyses of oxidative stress and apoptosis indices were conducted at the end of week 3 after surgery. In this study, L-T4 significantly enhanced learning and memory, improved motor balance and reduced the total number of rotations compared to the 6-OHDA-lesioned group. Biochemical analyses revealed that L-T4 enhanced the activity of superoxide dismutase (SOD) and catalase (CAT). It also lowered levels of lipid peroxidation and reduced the number of neurons dying through apoptosis in the striatum. These effects were seen when compared to the group that received 6-OHDA treatment. It was found that L-T4 treatment mitigated 6-OHDA induced motor and cognitive impairment, likely due to its antioxidant and anti-apoptotic effects. These findings propose that L-T4 may offer neuroprotective benefits for individuals with PD experiencing motor and memory deficits.
Mild Neonatal Hypoxia Modifies the Reactivity of the Glucocorticoid System in Adult Rats, Promoting Improved Learning and Spatial Memory Under Stressful Conditions.
Potapova S, Safarova D, Tyulkova E … +1 more , Vetrovoy O
Neurochem Res · 2026 Jan · PMID 41498834 · Publisher ↗
Mild neonatal hypoxia (NH) can serve as a conditioning stimulus that persistently modulates stress systems. We tested whether brief neonatal hypobaric hypoxia induces long-term changes hypothalamic-pituitary-adrenal (HPA...
Mild neonatal hypoxia (NH) can serve as a conditioning stimulus that persistently modulates stress systems. We tested whether brief neonatal hypobaric hypoxia induces long-term changes hypothalamic-pituitary-adrenal (HPA) regulation and adult behavior. Male Wistar rats received three 2 h hypobaric sessions on postnatal days 8-10. At 3 months, behavior was assessed. Biochemical measures included plasma/adrenal corticosterone (CORT), plasma ACTH, brain CORT, CRH/POMC/GR/11β-HSD2 protein, and HPA/steroidogenic gene expression. NH yielded a calmer, context-beneficial phenotype: startle latency increased, Morris water maze memory improved, whereas Barnes, recognition memory, and forced swim measures were unchanged. Hypothalamic CRH protein and pituitary/plasma ACTH were reduced, despite unchanged crh and Pomc mRNA, suggesting post-transcriptional control. Basal CORT in plasma and adrenals remained unchanged, but the CORT response to mild stress was larger and more sustained. In the adrenal glands, Cyp11b1 was selectively downregulated, whereas Mc2r, Cyp11a1, Hsd3b2, Cyp21a1 were unaffected. GR and 11β-HSD2 protein did not differ across tissues. In the brain, CORT decreased selectively in the amygdala. NH appears to act as developmental preconditioning, leading to persistent behavioral adaptations and altered HPA regulation in adulthood, characterized by reduced central drive at rest, preserved basal output, and efficient mobilization under challenge.
Valproate Releases the Latent Differentiation Capacity of Neuroblastoma by Targeting SP1/CDK4 Signaling.
Su M, Ma Y, Liu X … +6 more , Wu Y, Peng X, Xiong X, Huang K, Zhang S, Li Y
Neurochem Res · 2026 Jan · PMID 41484768 · Publisher ↗
Differentiation therapy represents a standard therapeutic regimen for high-risk neuroblastoma (HR-NB), demonstrating significant efficacy in suppressing tumor recurrence and improving patient survival rates. Retinoic aci...
Differentiation therapy represents a standard therapeutic regimen for high-risk neuroblastoma (HR-NB), demonstrating significant efficacy in suppressing tumor recurrence and improving patient survival rates. Retinoic acid (RA) remains the sole clinically approved differentiation-inducing agent for HR-NB, yet its therapeutic application is substantially limited by inherent drug resistance. Here, we found that valproate (VPA) exhibited dose-dependent inhibition of tumorigenicity in NB cells SH-SY5Y, SK-N-BE and retinoic acid (RA)-resistant SK-N-AS, along with the induction of G1-phase arrest and extensive neuronal differentiation. Subsequently, the transcriptomic landscape revealed that the impact of VPA on the biological processes of NB cells was predominantly enriched in the cell cycle pathway and Cyclin Dependent Kinase 4 (CDK4) as the most central gene. Additionally, we found that dual treatment with all-trans retinoic acid (ATRA) synergistically promotes NB cell differentiation, specifically in RA-resistant SK-N-AS cells. We therefore identify VPA as a therapeutic approach to dramatically enhance NB differentiation efficacy that could be used in combination with RA to improve patient outcomes, specifically for patients with RA-resistant HR-NB. These investigations will provide novel insights into cell cycle-mediated differentiation reprogramming in HR-NB.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe