Brain Res. [JOURNAL]
Sun
200 papers
Tauroursodeoxycholic acid alleviates depression-like behavior induced by chronic unpredictable mild stress through amelioration of catecholamine imbalance.
Spasojevic N, Stefanovic B, Ferizovic H … +4 more , Jankovic M, Virijevic K, Contos A, Dronjak S
Brain Res · 2026 Mar · PMID 41620195 · Publisher ↗
Depression is thought to emerge as a result of monoamine neuromodulators' deficiency in a specific central nervous system site. Tauroursodeoxycholic acid (TUDCA) has been found to have a protective role against diseases...
Depression is thought to emerge as a result of monoamine neuromodulators' deficiency in a specific central nervous system site. Tauroursodeoxycholic acid (TUDCA) has been found to have a protective role against diseases affecting the central nervous system. The potential effects of TUDCA on brain monoamine neurotransmitters in a stress-induced depression model have not been reported. We investigated the effects of TUCDA treatment on serotonin, norepinephrine and dopamine, catecholamine biosynthesis enzyme tyrosine hydroxylase (TH) and degrading enzyme monoamine oxidase A (MAO-A), NLRP3 and pro-inflammatory IL-1β in the hippocampus and mPFC of male rats subjected to chronic unpredictable mild stress (CUMS). Behavioral results demonstrated that TUDCA exhibits antidepressant and anxiolytic properties. TUDCA treatment markedly reduced the stress-increased the levels of IL-1β and NLRP3 in the hippocampus and mPFC of CUMS rats. Results showed that TUDCA treatment failed to alter serotonin levels in the hippocampus and mPFC, whereas it restored reduced dopamine and norepinephrine in the hippocampus and ameliorated dopamine imbalance in the mPFC of stressed rats. Further analysis showed that TUDCA treatment increases TH expression in the hippocampus and reduces the increased the protein levels of MAO-A in both brain areas. Our research suggests that TUDCA mitigated depressive-like behavior, and the mechanism appeared to be related to the regulation of catecholamine levels and their synthetic and degrading enzymes in both brain areas.
RhoA regulates morphine associated NMDA receptor signaling in the prelimbic region of medial prefrontal cortex pyramidal neurons.
Dong Q, Wang X, Wen Y … +5 more , Fu J, Zhang L, Zhang Y, Yan Z, Qu L
Brain Res · 2026 Mar · PMID 41617067 · Publisher ↗
Opioid dependence (OD) involves maladaptive neuroplasticity in brain reward circuits, particularly within the medial prefrontal cortex (mPFC). While RhoA and NMDA receptors (NMDARs) are implicated in addiction-related sy...
Opioid dependence (OD) involves maladaptive neuroplasticity in brain reward circuits, particularly within the medial prefrontal cortex (mPFC). While RhoA and NMDA receptors (NMDARs) are implicated in addiction-related synaptic plasticity, their specific interaction within mPFC subregions remains unclear. Using male Sprague-Dawley rats (6 weeks old), we investigated the role of RhoA signaling in the prelimbic cortex (PLC) via behavioral, molecular biological, and electrophysiological assays. Intra-PLC infusion of the RhoA inhibitor Rhosin significantly attenuated morphine-induced conditioned place preference and locomotor sensitization. Furthermore, repeated morphine administration (RMA) upregulated RhoA expression in layer 5 pyramidal neurons. In vitro whole-cell patch-clamp recordings of layer 5 neurons, stimulated at layer 2/3, revealed that Rhosin reduced the amplitude of synaptic NMDAR-mediated excitatory postsynaptic currents. Additionally, using an activity-dependent MK-801 block to isolate extrasynaptic components, we demonstrated that RhoA inhibition significantly attenuated extrasynaptic NMDAR activation, likely by limiting glutamate spillover during high-frequency stimulation. These findings elucidate a critical mechanism by which RhoA mediates opioid-induced neuroadaptations through the regulation of both synaptic and extrasynaptic NMDAR activity, identifying RhoA in the PLC as a promising therapeutic target for opioid dependence.
Therapeutic potential of iPSC-exosomes and miR-7 in Targeting Glioblastoma.
Yilmaz B, Savalan A, Ebrahimi A
Brain Res · 2026 Mar · PMID 41611050 · Publisher ↗
Exosomes play a vital role in intercellular communication, significantly influencing cell behavior and fate. Their influence is particularly evident in diseases like glioblastoma, one of the most challenging cancers to t...
Exosomes play a vital role in intercellular communication, significantly influencing cell behavior and fate. Their influence is particularly evident in diseases like glioblastoma, one of the most challenging cancers to treat. Due to glioblastoma's high resistance to conventional therapies, novel treatment strategies are urgently needed. Exosomes, being nano-sized vesicles capable of crossing the blood-brain barrier, can deliver bioactive molecules, including nucleic acids, proteins, and metabolites, to suppress tumor-promoting activities in cancer cells. Induced pluripotent stem cells (iPSCs), known for their unlimited proliferation potential and lack of ethical concerns compared to embryonic sources, present a valuable source of exosomes for therapeutic purposes. Although embryonic stem cell-derived exosomes have shown anti-tumor effects against glioblastoma, the therapeutic potential of iPSC-derived exosomes remains largely unexplored. In this study, we demonstrate that exosomes derived from iPSCs exert anti-tumorigenic effects on glioblastoma cells. We also focused on microRNAs (miRNAs), key regulators of cellular proliferation and apoptosis, which are considered promising therapeutic targets in glioblastoma. Specifically, we observed that microRNA-7 (miR-7) significantly inhibits glioblastoma cell proliferation, migration, and invasion. Our findings show that treatment with a miR-7-5p mimic reduces glioblastoma cell proliferation, and its combination with iPSC-derived exosomes leads to either additive or synergistic anti-cancer effects. These results highlight iPSC-derived exosomes and miR-7 as promising therapeutic candidates for glioblastoma and potentially other malignancies.
Covert attention modulates visual perception in early infancy.
Tsurumi S, Kanazawa S, Yamaguchi MK … +1 more , Kawahara JI
Brain Res · 2026 Mar · PMID 41611049 · Publisher ↗
Visual attention enhances perception by facilitating detection, localization, and identification of stimuli. Classic accounts propose that such modulation depends on feedback from higher cortical areas, whereas recent ev...
Visual attention enhances perception by facilitating detection, localization, and identification of stimuli. Classic accounts propose that such modulation depends on feedback from higher cortical areas, whereas recent evidence suggests contributions from feedforward processes within early visual regions. Infants provide a unique opportunity to test these mechanisms because their feedback pathways remain immature during the first half of the first year. Here, we examined whether covert attention influences perception in 3- to 4-month-old infants using a spatial cueing task. In Experiment 1, infants discriminated orientation, and in Experiment 2, they discriminated motion direction of cued peripheral gratings, despite not making eye movements. These findings demonstrate that covert attention modulates perception in early infancy, indicating that attentional effects can emerge via feedforward processes before the maturation of top-down feedback.
Audio-tactile association improves pitch perception in listeners with and without cochlear implants.
Hodges A, Fitzgerald MB, May L … +3 more , Lee RT, Goldsworthy RL, Fujioka T
Brain Res · 2026 Mar · PMID 41605410 · Publisher ↗
Auditory perception can improve when accompanied by somatosensory information, with beneficial effects for hard-of-hearing individuals. Further enhancement could occur by mapping discrete musical pitch information onto t...
Auditory perception can improve when accompanied by somatosensory information, with beneficial effects for hard-of-hearing individuals. Further enhancement could occur by mapping discrete musical pitch information onto tactile spatial patterns across four fingertips. Unlike previous studies, we used tactile stimuli that marked only the sound onsets via light pressure from air-inflated plastic membranes. Pre- and post-learning pitch discrimination tests used vocoded-audio only, vocoded-audio with tactile, and tactile-only conditions. The learning phase was a 10-minute nursery song melody listening task with the audio-tactile condition. In Exp. 1, normal-hearing listeners heard melodies in the original audio; in Exp. 2, normal-hearing listeners heard melodies with vocoded-audio; and cochlear implant (CI) users listened to the original audio. All groups performed best in the audio-tactile condition before the learning phase, and these immediate benefits were maximal at intermediate pitch intervals. Furthermore, CI users showed greater improvement in the audio-only condition after exposure, indicating the rapid transfer effect.
Loss of hepaCAM inhibits cholesterol biosynthesis and impairs learning and memory in mice.
Qiu Z, Liu Q, Zhang J
Brain Res · 2026 Mar · PMID 41605409 · Publisher ↗
Cholesterol is a major astrocyte-derived substance that reprograms neuronal lipid metabolism and regulates neuronal function upon uptake by neurons. However, the mechanisms controlling cholesterol biosynthesis and secret...
Cholesterol is a major astrocyte-derived substance that reprograms neuronal lipid metabolism and regulates neuronal function upon uptake by neurons. However, the mechanisms controlling cholesterol biosynthesis and secretion in astrocytes remain poorly understood. Here, we show that hepaCAM, an astrocytic membrane protein, is essential for normal memory function in mice by maintaining synaptic protein levels and synaptic spine density. Mechanistically, hepaCAM promotes neuronal function by modulating SREBP2-dependent cholesterol biosynthesis in astrocytes and facilitating its subsequent secretion. Furthermore, we identify the interaction of hepaCAM and ClC-2 is required for hepaCAM's regulatory role in cholesterol biosynthesis. Knockdown of hepaCAM in the hippocampus leads to reduced synaptic protein levels, decreased spine density, and impaired memory in mice. Collectively, our findings demonstrate that astrocytic hepaCAM regulates memory function through modulation of the astrocytic cholesterol biosynthesis pathway.
Single administration of vitamin C produces rapid antidepressant-like effects in female mice: A possible role of dopamine D2 receptor signalling.
Luo ML, Li YH, Gao XM … +2 more , Yang YJ, Jiang SZ
Brain Res · 2026 Mar · PMID 41577025 · Publisher ↗
BACKGROUND: The lifetime prevalence of depression is significantly higher in women. But the lack of ideal antidepressant severely limits therapies for female specific depressive disorders like perinatal depression. Herei...
BACKGROUND: The lifetime prevalence of depression is significantly higher in women. But the lack of ideal antidepressant severely limits therapies for female specific depressive disorders like perinatal depression. Herein, we evaluated whether vitamin C (ascorbic acid), a widely used nutritional supplement and perinatal therapeutic agent, could serve as a potential treatment for female-related depressive disorders using a chronic restraint stress (CRS) mouse model. METHODS: C57BL/6 adult female mice were submitted to a 14-day CRS paradigm to induce depression-like behaviors. The antidepressant potential of vitamin C (200 mg/kg, i.p., a single dose) were assessed in CRS-exposed female mice that exhibited depression-like phenotype. Furthermore, we explored the underlying mechanisms through RNA sequencing, western blotting, and pharmacological interventions. RESULTS: Vitamin C rapidly ameliorated depression-like phenotypes in CRS-exposed female mice within 24 h. The sucrose preference test indicated that the antidepressant effect of vitamin C lasted for more than 72 h. Transcriptome sequencing analysis revealed that vitamin C reversed CRS-induced transcriptional alterations in 104 genes in the medial prefrontal cortex (mPFC) of female mice, including the dopamine receptor D2 (D2R). Western blotting confirmed that CRS suppressed the D2R-ERK1/2-CREB-BDNF pathway in the mPFC, which was effectively rescued by vitamin C. The antidepressant effect of vitamin C was antagonized by the D2R antagonist sulpiride. Additionally, protein-protein interaction network analysis revealed functional linkages between D2R and other vitamin C-regulated stress-sensitive genes. CONCLUSIONS: Our findings suggest that vitamin C may serve as an ideal candidate for the treatment of depression in females, potentially through the restoration of the D2R-BDNF pathway.
Dynamic structural and metabolic changes during the epileptogenesis in the pilocarpine model of temporal lobe epilepsy: A longitudinal MRI study.
Pimentel-Silva LR, Barbosa R, Berenguer de Matos AH … +9 more , Casseb RF, de Campos BM, Cordeiro MM, Casseb JF, Dias EV, Vieira AS, Concha L, Lopes-Cendes I, Cendes F
Brain Res · 2026 Mar · PMID 41577024 · Publisher ↗
PURPOSE: We aimed to evaluate longitudinal structural and metabolic changes after induced status epilepticus (SE) in the pilocarpine model of TLE, over the three phases of epileptogenesis. METHODS: We analyzed 48 male ei...
PURPOSE: We aimed to evaluate longitudinal structural and metabolic changes after induced status epilepticus (SE) in the pilocarpine model of TLE, over the three phases of epileptogenesis. METHODS: We analyzed 48 male eight-week-old Wistar rats assigned to sham-control and SE-induced groups. T2-weighted images and 1H-MR spectra were acquired using a 3 T MRI clinical scanner (Philips Achieva) equipped with an animal coil. We measured hippocampal volumes (dorsal-HVol) and total N-acetylaspartate ratios to total creatine (tNAA/tCr) in four points in time (MRI-scan): baseline (before pilocarpine or sham treatments), 48 h (acute phase), 15 days (silent period), and 30 days (beginning of the chronic phase) after experimental treatment. To test differences in dorsal-HVol and hippocampal tNAA/tCr we built generalized linear mixed effects models including groups (pilo-SE and control) and MRI-scan as main effects and a group*MRI-scan interaction. RESULTS: Pilo-SE and control animals showed similar baseline dorsal-HVol and hippocampal tNAA/tCr (both p > 0.1). Pilo-SE showed reduced dorsal-HVol and tNAA/tCr at all MRI-scans (all p < 0.001) when compared to controls. Intragroup analysis revealed that dorsal-HVol and tNAA/tCr significantly increased at 15- and 30-days (all p < 0.001) when compared to 48 h, although remaining lower than the baseline scan. There were no changes over time in sham-controls (all p > 0.4). CONCLUSIONS: The novelty of our study was to analyze non-invasively structural and metabolic markers of hippocampal dysfunction across the three main phases of pilocarpine-induced epileptogenesis in comparison to the typical brain development over the same period. Acute dorsal hippocampal volume loss and hippocampal neuronal dysfunction are present as early as 48 h post-pilocarpine-induced SE, dynamically changing over time. This acute damage is followed by a pattern of gradual recovery throughout the silent and chronic phases of epileptogenesis, though with an offset for the pilo-SE group. A better understanding of the course of noninvasive markers of epileptogenesis and HS may contribute to stablish surrogate endpoints in interventions to treat or prevent focal epilepsy.
Inflammation-induced Neuronal Damage in CNS Tuberculosis: Molecular Mechanism and Therapeutic Targets.
Ahmad S, Husain A, Jain P … +1 more , Ahmad F
Brain Res · 2026 Mar · PMID 41558621 · Publisher ↗
BACKGROUND: Central nervous system tuberculosis (CNS-TB), most frequently manifesting as tuberculous meningitis, is associated with high mortality and significant long-term neurological morbidity. Increasing evidence sug...
BACKGROUND: Central nervous system tuberculosis (CNS-TB), most frequently manifesting as tuberculous meningitis, is associated with high mortality and significant long-term neurological morbidity. Increasing evidence suggests that disease severity and neurological damage are driven largely by dysregulated host neuroinflammatory responses rather than direct Mycobacterium tuberculosis-mediated cytotoxicity. However, the mechanistic links between glial activation, inflammatory signaling, and neuronal injury remain incompletely defined. MATERIALS AND METHODS: A comprehensive literature review was conducted using PubMed, Scopus, and Web of Science databases to identify experimental, clinical, and translational studies investigating neuroimmune mechanisms in CNS-TB. Studies focusing on glial activation, cytokine signaling, oxidative stress, excitotoxicity, mitochondrial dysfunction, and neuronal death were included. Recent advances in single-cell transcriptomics, immunometabolism, and host-directed therapeutic strategies were also analyzed and integrated. RESULTS: The reviewed evidence indicates that CNS invasion by M. tuberculosis leads to sustained activation of microglia and astrocytes, resulting in excessive production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. This inflammatory milieu disrupts blood-brain barrier (BBB) integrity, promotes leukocyte infiltration, and induces oxidative and nitrosative stress. Astrocyte dysfunction further contributes to excitotoxicity through impaired glutamate clearance. These converging inflammatory, oxidative, and excitotoxic pathways drive mitochondrial dysfunction, synaptic impairment, and activation of regulated neuronal cell death pathways, culminating in neurodegeneration. CONCLUSION: CNS-TB-associated neuronal injury arises primarily from maladaptive host neuroimmune responses rather than direct mycobacterial effects. A unifying framework centered on glial-driven inflammation and mitochondrial dysfunction provides critical insight into disease pathogenesis. Targeting these convergent pathways through host-directed therapies, alongside antimicrobial treatment, represents a promising strategy to mitigate neuroinflammation and improve long-term neurological outcomes in CNS tuberculosis.
Genetics of Autism Spectrum Disorder underscores the role of altered spontaneous neuronal activity as a catalyst for the neurodevelopmental anomalies.
Dey S, Das A
Brain Res · 2026 Mar · PMID 41539592 · Publisher ↗
Autism Spectrum Disorder (ASD) represents a diverse set of neurodevelopmental disorders diagnosed in children exhibiting common behavioral impairments in social communication and excessive repetitive behaviors. Genetic a...
Autism Spectrum Disorder (ASD) represents a diverse set of neurodevelopmental disorders diagnosed in children exhibiting common behavioral impairments in social communication and excessive repetitive behaviors. Genetic approaches and large-scale genomic studies have uncovered hundreds of ASD-associated genes with diverse molecular functions contributing to various biochemical and physiological pathways. Despite the underlying genetic diversity, the convergence of phenotypic features suggests the disruption in shared neurobiological mechanisms contributing to ASD. Spontaneous neuronal activity (SNA), the stimulus-independent firing of neurons, which is observed even during neuronal development, has been known to be crucial for neural circuit maturation. Functional neuroimaging studies have demonstrated that SNA is a central process disrupted in ASD patients and mutation-based animal and cellular models. SNA orchestrates critical developmental programs during neuronal maturation such as dendritic arborization, synaptic pruning, excitatory-inhibitory balance, and activity-dependent transcriptional regulation. Perturbations in these dynamics may provide a unifying mechanistic framework linking genetic mutations to abnormal circuit formation and behavioral anomalies. In this review, we collate the genetic and genomic studies to evaluate the contribution of ASD genes in regulating the spontaneous firing of neurons. We classify ASD genes into generators, sensors, transducers, and responders of activity-induced signals and discuss their roles in regulating membrane excitability, transducing the signal to cytoplasmic or nuclear targets to transform the neuronal gene expression program, eventually impacting neuronal and synaptic development. We attempt to substantiate the contribution of altered SNA as the single major common neurological mediator connecting genetic mutations with the common behavioral irregularities manifested in ASD.
The oral-gut-brain axis in periodontitis: microbial signaling in systemic and neuroinflammatory disease.
Pravin V, Vellapandian C, Naveen Kumar V
Brain Res · 2026 Mar · PMID 41539591 · Publisher ↗
Periodontitis, a chronic inflammatory disease of the oral cavity, has been identified as a modifiable risk factor of the development of systemic and neurological disorders via a complicated interplay of microbiological,...
Periodontitis, a chronic inflammatory disease of the oral cavity, has been identified as a modifiable risk factor of the development of systemic and neurological disorders via a complicated interplay of microbiological, immunological, and neural interactions. Periodontal pathogens breach local immune homeostasis, are translocated to the gut and brain, and trigger a cascade of immune deregulation, leaky gut, and blood-brain barrier, thereby forming a tri-directional communication network that links local oral inflammation to systemic and neurovascular conditions. This review synthesizes existing evidence on how oral dysbiosis, can spread to the gut and trigger systemic inflammation, leading to neuroinflammation and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Mechanistically, the OGB axis acts through various processes, such as hematogenous spread, retrograde axonal transport, immune cell trafficking (Trojan horse mechanism), and extracellular vesicle-based signaling corresponding to the causes of neuroinflammation, microglial activation, and the pathology of tau and amyloid. The diagnostic and therapeutic implications of the OGB axis provide new pathways toward early intervention with precision medicine, microbiome remodeling, immune-based therapy, and neuroprotective approaches. Emerging technologies, including AI-based diagnostics and biosensing technologies, offers noninvasive tools to track host-microbial interactions and inflammatory biomarkers. This integrative view underscores the central importance of oral health in systemic homeostasis and the development of neurodegenerative conditions, necessitating collaborative approaches between dentistry, neurology, and immunology to cooperate to deliver efficacy in disease elimination and mitigation.
Key optogenetic advances in retinal prostheses: A comparative narrative review.
Zahran L, Elnabawy RH
Brain Res · 2026 Mar · PMID 41534822 · Publisher ↗
This narrative review examines optogenetic strategies for retinal prostheses, which represent an advanced step in vision restoration, particularly for patients with retinitis pigmentosa and age-related macular degenerati...
This narrative review examines optogenetic strategies for retinal prostheses, which represent an advanced step in vision restoration, particularly for patients with retinitis pigmentosa and age-related macular degeneration. This review highlights the use of optogenetic stimulation to target high-density retinal ganglion cells (RGCs), focusing on developments like the FlexLED device. Opsins such as ChR2, ReaChR, and ChrimsonR, engineered for light sensitivity and faster responses, are critical for enhancing vision restoration. Combining optogenetic and electrical stimulation improves the reproducibility and specificity of RGC responses. Neuroimaging techniques like adaptive optics scanning laser ophthalmoscopy (AOSLO) help monitor cell activity, aiding in the development of visual repair methods. However, challenges remain in improving opsin sensitivity, gene delivery techniques, and ensuring long-term efficacy of retinal responses in patients. This review emphasizes the potential of optogenetic retinal prostheses to offer lasting, effective vision rehabilitation, significantly improving the quality of life for patients. This narrative review emphasizes that further research is needed to overcome current obstacles, such as improving opsin sensitivity and gene delivery techniques, to ensure long-term, effective vision restoration in patients.
Multi-biofluid metabolomics coupled with gene network reveals stage-specific alterations in mild cognitive impairment and Alzheimer's disease in an ethnically mixed cohort.
Cadaxo AS, Cotrin JC, Valente AP … +6 more , Lopes FG, Veras RP, Torres DS, Molina da Costa RQ, Dos Santos Junior GC, Santos-Rebouças CB
Brain Res · 2026 Mar · PMID 41534821 · Publisher ↗
Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder worldwide. A prodromal stage, often manifested as Mild Cognitive Impairment (MCI), can precede dementia onset. Metabolomics provides a...
Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder worldwide. A prodromal stage, often manifested as Mild Cognitive Impairment (MCI), can precede dementia onset. Metabolomics provides a powerful approach to detect metabolic alterations capturing combined genetic, epigenetic, dietary, gut microbiota, and environmental influences on AD pathogenesis and progression from MCI to AD. In this study, we analysed plasma, urine, and saliva metabolomes of 94 ethnically diverse Brazilian individuals (30 AD, 16 MCI and 48 healthy controls), all comorbidity-free, using Nuclear Magnetic Resonance (NMR)-based metabolomics. Cross-sectional analysis employed multivariate modelling (PLS-DA) and univariate Mann-Whitney U tests. We identified distinct group-specific metabolic signatures involving amino acids (phenylalanine, glutamine, asparagine, valine, alanine), energy-related metabolites (pyruvate, citrate, glucose), compounds linked to lipid/redox pathways (acetate, glutamate, aspartate), epigenetic regulation (betaine), neuroinflammation, immune fitness, and gut microbiome-influenced metabolites (scyllo-inositol). Valine increased progressively (controls < MCI < AD), while alanine showed a biphasic pattern (reduced in MCI, elevated in AD). These consistent, biofluid-spanning alterations highlight their potential as minimally invasive biomarkers for diagnosis and monitoring. Integration of metabolite data with AD-associated genes from genome-wide association studies (GWAS) revealed six genes (CYCS, NFAT5, GRIN2B, SLC43A2, MAPT, and SLC38A1) common to all biofluids, reinforcing convergent systemic pathways. Collectively, these findings underscore the importance of integrating metabolomics with genetic networks to enhance understanding of AD pathophysiology, identify potential therapeutic targets, and guide future clinical validation and precision medicine strategies for dementia in ethnically mixed populations.
Dehydrocorybulbine blocks the Lyn-mediated MAPK pathway to promote anti-inflammatory polarization of microglia in mice after sevoflurane anesthesia.
Zhang B, Tian W
Brain Res · 2026 Mar · PMID 41529779 · Publisher ↗
Dehydrocorybulbine (DHCB) has demonstrated efficacy in alleviating thermally induced acute pain. The present study sought to study the impact of DHCB on postoperative cognitive dysfunction (POCD). Mice or mouse BV2 cells...
Dehydrocorybulbine (DHCB) has demonstrated efficacy in alleviating thermally induced acute pain. The present study sought to study the impact of DHCB on postoperative cognitive dysfunction (POCD). Mice or mouse BV2 cells were exposed to sevoflurane for modeling. Behavioral tests (Morris water maze, Y-maze, and novel object recognition test) and western blot analysis of APP, p-Tau (Thr231), and Tau protein expression in mouse hippocampal tissues were conducted to analyze cognitive impairment. DHCB inhibited M1 polarization of BV2 cells and mediated anti-inflammatory M2 polarization, further alleviating inflammatory damage. DHCB also alleviated cognitive impairment in mice dose-dependently by promoting the polarization of M1 to M2 microglia in the hippocampal CA1 region. DHCB targeted and inhibited the expression of Lck/Yes-related novel protein tyrosine kinase (Lyn) protein in microglia, thereby suppressing p38 MAPK signaling transduction. Reactivating Lyn reversed the above benefits of DHCB. Similarly, p38 MAPK signal inhibitor SB 202190 opposed the proinflammatory polarization of BV2 cells and inflammatory damage mediated by Lyn overexpression. In conclusion, our study demonstrates that DHCB inhibits Lyn expression in microglia, thereby suppressing p38 MAPK signal transduction and accelerating the polarization of microglia from M1 to M2 phenotype to alleviate sevoflurane-induced POCD.
Programmed cell death pathways in Parkinson's disease: Spotlight on ferroptosis and pyroptosis.
Sharma V, Verma R, Sharma P … +1 more , Singh TG
Brain Res · 2026 Mar · PMID 41529778 · Publisher ↗
Parkinson's disease (PD) characterized by the selective loss of dopaminergic neurons in the brain resulting in motor and cognitive deficits. While apoptosis has long been considered a primary mechanism of neuronal death...
Parkinson's disease (PD) characterized by the selective loss of dopaminergic neurons in the brain resulting in motor and cognitive deficits. While apoptosis has long been considered a primary mechanism of neuronal death in PD, emerging evidence highlights the significant roles of non-apoptotic programmed cell death pathways, particularly ferroptosis and pyroptosis-in driving PD progression. Ferroptosis is form of cell death that is dependent on iron and driven by lipid peroxidation, appears to be associated with PD. On the other hand, Pyroptosis, a caspase-1-dependent inflammatory cell death pathway mediated by activation of inflammasome and release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and IL-18. Both pathways contribute to the neurodegeneration in PD through distinct yet interconnected pathways. Therefore, this review highlights molecular mechanisms underlying ferroptosis and pyroptosis in PD and recent advances in pharmacological strategies targeting these pathways.
EAE models of neuropathic pain in multiple sclerosis do not require pertussis toxin.
Lamerand SR, Basu P, Gakii NE … +2 more , Steber SS, Taylor BK
Brain Res · 2026 Mar · PMID 41529777 · Publisher ↗
BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is a preclinical model of multiple sclerosis (MS), typically induced with two inoculations of myelin oligodendrocyte glycoprotein (MOG) emulsified in complete F...
BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is a preclinical model of multiple sclerosis (MS), typically induced with two inoculations of myelin oligodendrocyte glycoprotein (MOG) emulsified in complete Freund's adjuvant (CFA), and supplemented with pertussis toxin (PTX). Although PTX has been considered essential, recent studies suggest that EAE pathology can develop without it. OBJECTIVES: Indices of clinical disease and neuropathic pain were evaluated in a conventional model of EAE that included PTX (EAE-PTX) and one that lacked PTX (EAE-nPTX), as well as in multiple control groups that lacked MOG (CFA-PTX and CFA-nPTX). METHODS: A battery of behavioral tests were used to evaluate motor dysfunction and hypersensitivity to mechanical, cold, and heat stimuli with a repeated-measures design in male and female C57BL/6 mice. One month after the first EAE inoculation, fluoromyelin staining was used to evaluate demyelination in spinal cord, cortex, and peripheral nerve, while ATF3 was used as a marker of injury in sensory neurons of lumbar L4-L5 dorsal root ganglia (DRG). RESULTS: Compared to CFA-PTX and CFA-nPTX controls, both EAE-PTX and EAE-nPTX groups developed motor dysfunction, behavioral hypersensitivity, and demyelination in ventral spinal cord but not cortex. Spinal demyelination was greater in EAE-nPTX than in EAE-PTX. ATF3 was detected in lumbar DRG of all EAE and CFA control groups, suggesting that systemic inflammation, rather than MOG-driven neuropathology, contributes to neuron damage. CONCLUSIONS: PTX is not required for the manifestation of motor dysfunction and neuropathic pain in MOG-based EAE models. Newer EAE-nPTX models have the distinct advantage of mimicking MS disease while avoiding confounding effects of pertussis toxin.
The mechanism of Calhm2 regulating the expression of CaMKIIα in spinal dorsal horn involved in the pathogenesis of bone cancer pain.
Xiong M, Li X, Su S … +5 more , Xu X, Yu J, Tian W, Wang L, Ke C
Brain Res · 2026 Mar · PMID 41520863 · Publisher ↗
Bone cancer pain (BCP) is one of the most common and debilitating types of pain in cancer patients, severely impairing the quality of life in advanced stages of the disease. However, its underlying mechanisms remain poor...
Bone cancer pain (BCP) is one of the most common and debilitating types of pain in cancer patients, severely impairing the quality of life in advanced stages of the disease. However, its underlying mechanisms remain poorly understood, highlighting the urgent need to clarify its pathogenesis and identify novel therapeutic targets. Increasing evidence suggests that altered excitability of spinal dorsal horn neurons is a prerequisite for pain generation. The dynamic balance of intracellular and extracellular calcium ion concentrations is critical for maintaining normal neuronal excitability. In this study, we investigated the role of calcium homeostasis modulator 2 (Calhm2) in BCP. In BCP mice, the expression of Calhm2 in the spinal dorsal horn was significantly upregulated, accompanied by a concomitant increase in calcium/calmodulin-dependent protein kinase II α (CaMKIIα). Lentiviral-mediated knockdown of Calhm2 in the spinal dorsal horn reduced CaMKIIα expression, alleviated mechanical allodynia, and decreased c-fos expression. These findings suggest that Calhm2 regulates CaMKIIα to promote neuronal activation in the spinal dorsal horn, thereby contributing to the development of bone cancer pain. Calhm2 may represent a promising target for therapeutic intervention in BCP.
Aperiodic slope reflects glutamatergic tone in the human brain.
Sheldon AA, Moser HR, Abdullahi KS … +6 more , Allison KD, Mulder CB, Montoya SA, Sponheim SR, Marjańska M, Schallmo MP
Brain Res · 2026 Mar · PMID 41520862 · Full text
Excitatory and inhibitory neural processes are essential for every aspect of brain function, but current non-invasive neuroimaging methods to study these in the human brain are limited. Recent studies which separate osci...
Excitatory and inhibitory neural processes are essential for every aspect of brain function, but current non-invasive neuroimaging methods to study these in the human brain are limited. Recent studies which separate oscillatory and aperiodic components of electrophysiological power spectra have highlighted a relationship between aperiodic activity and functional brain states. Studies in both animal models and humans suggest that the aperiodic slope of electrophysiological power spectra reflects the local balance of excitatory:inhibitory (E:I) synaptic transmission. Aperiodic slope varies across individuals, brain states, and clinical populations, which may reflect important differences in E:I balance. However, there is currently a lack of evidence linking aperiodic slope to other measures of excitation and inhibition in the human brain. Here, we show that flatter (less steep) aperiodic slopes from human electroencephalography (EEG) are associated with higher concentrations of the excitatory neural metabolite glutamate measured with 7 T magnetic resonance spectroscopy (MRS) in the occipital lobe at rest. This suggests that individual differences in aperiodic neural activity reflect cortical glutamate concentrations, providing important insight for understanding changes in neural excitation across brain states and neuropsychiatric populations (e.g., schizophrenia) where glutamatergic function may differ. Our results support the use of aperiodic slope as a non-invasive marker for excitatory tone in the human brain.
From truth to deception: a network control theory perspective on brain connectivity and cognitive dynamics.
Rahimi Saryazdi A, Ghassemi F, Parastesh F … +2 more , Rajagopal K, Jafari S
Brain Res · 2026 Mar · PMID 41520861 · Publisher ↗
Deception represents a sophisticated mental activity that modifies the brain's dynamic operations. Understanding how brain activity changes during deceptive behavior is important for both cognitive neuroscience and pract...
Deception represents a sophisticated mental activity that modifies the brain's dynamic operations. Understanding how brain activity changes during deceptive behavior is important for both cognitive neuroscience and practical applications such as lie detection. Recently, network control theory (NCT) has emerged as a novel tool that combines principles from network science and control theory, offering a powerful framework for quantifying how easily the brain can transition between different cognitive states. In this study, NCT is applied for the first time to examine the effects of deception on brain functional connectivity (FC). Electroencephalogram signals are recorded from 22 participants during a visual task designed to elicit deception. The phase lag index method is then employed to construct FC networks for both truthful and deceptive conditions. The brain is modeled as a linear dynamical system, and two control metrics, average controllability and modal controllability, are computed across five frequency bands: delta, theta, alpha, beta, and gamma. The results reveal significant differences in brain dynamics between the two conditions. In the delta and beta bands, average controllability is significantly higher during truthful responses (p-value < 0.005), while in the gamma band, it is elevated during deception. Additionally, in the beta and gamma bands, modal controllability is significantly higher during deceptive responses (p-value < 0.005). It is observed that during deception, the control energy spectrum shifts from predominance in lower frequencies, which is more evident in truthful responses, toward higher frequencies where energy increases during deception. The outcomes imply that brain connectivity patterns are affected by deceptive behavior and highlight the potential of NCT in advancing deception-related investigations.
K-means++ guided multi-view CNN with channel attention for EEG emotion recognition.
Zhou Y, Jiang R, Zhang J
Brain Res · 2026 Mar · PMID 41520860 · Publisher ↗
The use of artificial intelligence for emotion recognition is the focus of improving human-computer interaction. Recently, deep learning has been widely used in the study of emotion recognition. However, how to correctly...
The use of artificial intelligence for emotion recognition is the focus of improving human-computer interaction. Recently, deep learning has been widely used in the study of emotion recognition. However, how to correctly identify emotions still faces a huge challenge. We propose a multi-view deep CNN based on channel attention (MVACNN) for EEG emotion recognition. MVACNN first clustered the channels and divided the channels with high similarity into the same view. Channels within the same view have highly similar patterns of neural activity, which can extract the synergistic features of specific brain regions more intensively and reduce the interference of irrelevant noise. To extract more discriminative features, MVACNN integrates channel attention into each view. Channel attention gives different channel weights to effectively learn the importance of different channels. In addition, MVACNN uses residual blocks to learn the residual variation to better represent the relationship between input and output. The residual structure preserves the original information, improving feature utilization and thus maintaining performance. Experimental results show that MVACNN achieves good results on different datasets.
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