Brain Research[JOURNAL]
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200 papers
Exacerbation of sensory dysfunction by hematoma-induced circuitry damage in a mouse model of thalamic hemorrhage.
Wu Y, Deng J, Hao S … +2 more , Hu N, Wang B
Brain Res · 2026 Sep · PMID 42092577 · Publisher ↗
Sensory impairment following stroke is a prevalent and challenging complication that imposes significant burdens and risks on patients. Despite the frequency of hemorrhage-induced sensory impairments in the thalamus, a c...
Sensory impairment following stroke is a prevalent and challenging complication that imposes significant burdens and risks on patients. Despite the frequency of hemorrhage-induced sensory impairments in the thalamus, a comprehensive understanding of the underlying mechanisms and therapeutic targets remains incomplete. Here, we examine circuit connectivity and electrophysiological properties to study pathogenesis, as well as molecular target efficacy. Using a mouse model of thalamic hemorrhage and conducting behavioral assessments, thalamic hemorrhage can induce specific sensory dysfunction. Within the context of thalamic-related circuitry connections, damage thresholds in upstream circuits are higher compared to downstream regions. Electrophysiological characterization revealed that post-hemorrhagic thalamic neurons exhibited narrower action potential (AP) widths and reduced decay times, indicating heightened neuronal excitability. Additionally, transcriptomic analysis identified the PI3K-AKT signaling pathway and pharmacological inhibition targeting this pathway significantly mitigated the severity of sensory impairments. These findings provide novel insights into the pathogenesis of sensory impairments and present potential therapeutic targets for post-hemorrhagic sensory impairments.
Peripheral GABAergic markers in late-life depression: Links to clinical outcomes.
Rezaei S, Sibille E, Voineskos D … +4 more , Rajji TK, Nikolova YS, Diniz BS, Vieira EL
Brain Res · 2026 Sep · PMID 42086139 · Publisher ↗
Late-life depression (LLD) is a debilitating condition, characterized by mood disturbance and cognitive decline. Gamma-aminobutyric acidergic (GABAergic) deficits are a hallmark of both aging and depression; however, few...
Late-life depression (LLD) is a debilitating condition, characterized by mood disturbance and cognitive decline. Gamma-aminobutyric acidergic (GABAergic) deficits are a hallmark of both aging and depression; however, few studies have examined the GABAergic system in LLD. We hypothesized that there would be significant decrease in peripheral GABA levels and γ-aminobutyric acid type A (GABA-A) receptor subunit expression in individuals with LLD compared to healthy controls (HC). In this study, we measured plasma GABA levels and the mRNA expression of four GABA-A receptor subunits (GABRA1, GABRA4, GABRA5, and GABRR2) in peripheral blood mononuclear cells (PBMCs) from 87 older adults (LLD, n = 46; HC, n = 41). Plasma GABA levels were quantified using enzyme-linked immunosorbent assay (ELISA), and receptor subunit expression was assessed by quantitative-real time (RT-qPCR). There were no significant differences between LLD and HC in plasma GABA levels or GABA-A receptor subunit expression. In LLD, within-group analyses showed GABRA5, GABRR2, GABRA4, GABRA1 expression were negatively correlated with cognitive performance on the Montreal Cognitive Assessment MoCA scores (ρ = -0.464, p = 0.045, ρ = -0.515, p = 0.041; ρ = -0.414, p = 0.078, and ρ = -0.477, p = 0.062 respectively). This is the first study that investigated GABA-A receptor subunit expression in the periphery of individuals with LLD. Our findings suggest that altered peripheral GABA-A receptor subunit expression, even in the absence of between-group differences, is associated with reduced cognitive function in LLD.
uPAR exhibits age- and region-dependent expression in the brains of mice with Alzheimer's disease-like pathology.
Sarko LE, Klaus E, Bondarenko V … +8 more , Secker C, Mnuk MS, Marino KM, Shippy DC, Ulland TK, Saha K, Emborg ME, Metzger JM
Brain Res · 2026 Sep · PMID 42081929 · Full text
The urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored cell surface protein that regulates leukocyte adhesion, migration, and activation, thereby contributing to inflammation and tissue remodeling. Ho...
The urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored cell surface protein that regulates leukocyte adhesion, migration, and activation, thereby contributing to inflammation and tissue remodeling. However, its role in Alzheimer's disease (AD), particularly in relation to glial dysfunction, remains poorly defined. Here, we investigated the temporal and spatial regulation of uPAR expression across AD mouse models with intact or deficient adaptive immunity. Using immunohistochemistry, we assessed uPAR expression in Rag2/Il2rg (Rag), Rag2/Il2rg-5xFAD (Rag-5xFAD), C57BL/6 (WT), and 5xFAD mice across multiple brain regions. uPAR expression increased with age and was significantly elevated in 5xFAD mice, with robust upregulation evident by 6 months irrespective of immune status. Immunofluorescence revealed that uPAR localized predominantly to Iba1 microglia clustered around Aβ plaques, with limited neuronal expression. Bulk RNA sequencing of Rag-5xFAD brain tissue demonstrated enrichment of disease-associated microglia (DAM) and senescence-related transcriptional programs. These findings indicate that uPAR marks a subset of plaque-associated glial cells undergoing functional and transcriptional remodeling in AD, independent of peripheral adaptive immune signaling. Collectively, our results identify uPAR as a marker of dysfunctional, DAM-like microglia and implicate it in senescence-associated neuroinflammatory pathways. This work provides a framework for future studies targeting uPAR-expressing glial populations as a potential therapeutic strategy in AD.
Neurochemical impact of psychostimulants: Longitudinal MRI analysis of brain iron content in children with ADHD.
Morandini HAE, Vos SB, Chivers P … +2 more , Silk TJ, Rao P
Brain Res · 2026 Sep · PMID 42081928 · Publisher ↗
BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in school-aged children and has been associated with impaired brain iron homeostasis. Evidence has shown that psychostim...
BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in school-aged children and has been associated with impaired brain iron homeostasis. Evidence has shown that psychostimulant treatment may affect brain iron content in children with ADHD, however, longitudinal evidence remains limited. The present longitudinal study investigated the effect of psychostimulant treatment duration and age at treatment onset on brain iron content in children with ADHD. METHODS: Neuroimaging and phenotypical data were collected from the publicly available Oregon ADHD-1000 dataset. After screening, data from 29 psychostimulant-medicated children with ADHD and 38 neurotypical children were included. Individual General Estimating Equation (GEE) models were used to investigate the effect of groups, treatment duration and age at treatment onset on brain iron content across time. Bonferroni correction was applied for multiple comparisons. RESULTS: GEE analyses revealed no significant group effect on nigral, thalamic and striatal iron content. However, a significant group effect was found in the globus pallidus, with lower iron content in psychostimulant-medicated children with ADHD compared to their NT peers. Within the ADHD group, Bonferroni corrected post hoc comparison showed that earlier treatment onset (≤ 8 years) was associated with significantly higher iron content in the basal ganglia and thalamus compared to later treatment onset (≥ 9 years). CONCLUSION: Evidence has shown that medication-naïve children with ADHD may exhibit lower brain iron content compared to NT children and the current findings suggest that age at psychostimulant treatment onset, rather than treatment duration, may influence brain iron content in children with ADHD.
The activity of D2 dopamine receptors of the ventral tegmental area changed the induced- cognitive responses of the lateral hypothalamic cholinergic stimulation following neuropathic pain.
Kohandani M, Mohammadi MT, Bahari Z … +3 more , Marefati N, Mohammadi A, Raei M
Brain Res · 2026 Sep · PMID 42069242 · Publisher ↗
BACKGROUND: Dopaminergic neurons within the ventral tegmental area (VTA) is involved in the development of cognitive dysfunction during chronic pain. It is controlling cognitive behaviors via its various projection pathw...
BACKGROUND: Dopaminergic neurons within the ventral tegmental area (VTA) is involved in the development of cognitive dysfunction during chronic pain. It is controlling cognitive behaviors via its various projection pathways to different areas in the brain including lateral hypothalamus (LH). The activation of LH induced analgesia during chronic pain. In the current study, we assessed whether D2 dopamine receptors activity within the VTA can change the induced-cognitive responses of LH following its cholinergic stimulation during neuropathic pain in rats. Aditionally, we assessed whether cholinergic stimulation of LH can change firing rate of VTA neurons. METHODS: Male Wistar rats were implanted with two separate cannulae into the LH and VTA on the same side. After 4 days' recovery of cannulation surgery, animals underwent second surgery for induction of neuropathic pain (chronic constriction injury of sciatic nerve, CCI). Citicoline (1 µg/1µl normal saline), as an acetylcholine precursor, that activates the LH projecting neurons, were microinjected into the LH. In the other groups, D2-like dopamine receptor antagonist, sulpiride (1 µg/1µl normal saline) or agonist, bromocriptine (1 µg/1µl normal saline) were microinjected into VTA, 5 min prior intra-LH injection of citicoline. Cognitive and electrophysiology studies were assessed 15-30 minutes after drug injection. RESULTS: Stimulation of LH via citicoline significantly induced analgesic and learning/memory enhancer effects. Additionally, intra-VTA injection of bromocriptine significantly increased analgesic and learning/memory enhancer effects of LH. Interestingly, sulpiride significantly decreased analgesic and learning/memory enhancer effects of LH. Stimulation of LH via citicoline effectively increased firing rate of VTA neurons. Intra-VTA injection of bromocriptine and sulpiride significantly increased and decreased firing rate of VTA neurons, respectively. CONCLUSION: The present study suggest that the analgesic and memory enhancer effects which produced by LH cholinergic stimulation is mediated by D2-like dopamine receptors of VTA in neuropathic pain. Additionally, the cholinergic stimulation of LH via citicoline can increase firing rate of VTA neurons during neuropathic pain and intra-VTA injection of sulpiride effectively reversed the effects of citicoline on firing rate of VTA neurons.
Generalization of familiarity-related neural patterns to emotional facial expressions.
Ely MM, Ambrus GG
Brain Res · 2026 Aug · PMID 42067009 · Publisher ↗
Emotional facial expressions are known to bias face processing, yet it remains unclear whether such effects extend to neural signals associated with face familiarity. In this secondary analysis of openly available EEG da...
Emotional facial expressions are known to bias face processing, yet it remains unclear whether such effects extend to neural signals associated with face familiarity. In this secondary analysis of openly available EEG data, we used cross‑dataset multivariate pattern analysis (MVPA) to test whether established neural signatures of face familiarity generalize across emotional expressions. Participants viewed faces in two independent experiments: one involving explicit emotion categorization (happy, angry, sad, neutral) and another involving personally familiar and unfamiliar identities. Classifiers trained to distinguish familiar from unfamiliar faces were cross‑applied to emotional expressions, and vice versa, using complementary relabeling strategies. Across analyses, neural patterns for angry expressions showed the strongest and most sustained generalization to familiarity‑related neural signals, emerging around 200 ms post‑stimulus and persisting throughout the trial (peak Cohen's d = 1.35 over posterior regions). Neural patterns for happy and sad expressions showed weaker and more transient generalization (200-400 ms), while neutral expressions consistently aligned with patterns for unfamiliarity. These findings demonstrate that threat‑related facial expressions exhibit neural dynamics that show convergence in pattern structure with established familiarity signals, extending prior evidence that emotional expressions, particularly anger, systematically modulate face representations beyond identity.
Integrated metabolomics and network pharmacology leveraging UPLC-Q-TOF-MS reveal material basis and metabolic mechanisms underlying Tongqiao Huoxue Decoction's efficacy in cerebral infarction.
Wang T, Bai L, Liu S … +6 more , Wang R, Li Q, Xu J, Yang M, Dong P, Han H
Brain Res · 2026 Sep · PMID 42067008 · Publisher ↗
Cerebral infarction (CI) is a common manifestation of stroke, which is a form of cerebral ischaemia. Tongqiao Huoxue Decoction (THD) is a proven therapeutic formulation for stroke treatment. As a therapeutic formulation...
Cerebral infarction (CI) is a common manifestation of stroke, which is a form of cerebral ischaemia. Tongqiao Huoxue Decoction (THD) is a proven therapeutic formulation for stroke treatment. As a therapeutic formulation renowned for promoting blood circulation and removing blood stasis, it is widely applied in clinical practice. However, the molecular mechanisms underlying its therapeutic effects are not yet clear. The purpose of this study is to evaluate the therapeutic effects of THD in CI rats and to delve into its potential mechanisms of action through pharmacodynamic experiments and metabolomic analysis. Results demonstrated that THD treatment was associated with reduced symptoms and metabolic disturbances in CI rats. Metabolomics analysis revealed the therapeutic effects of THD, modulating levels of 31 differential metabolites in urine and 41 in blood. These effects were associated with biosynthesis of unsaturated fatty acid, Glycerophospholipid metabolism, Arachidonic acid metabolism, Sphingolipid metabolism, Taurine and Hypotaurine metabolism, Glutathione metabolism, Linoleic acid metabolism. Network pharmacology revealed 49 bioactive compounds targeting 407 targets involved in Lipid and atherosclerosis, PI3K-Akt signaling, and Calcium signaling pathways. Finally, molecular docking analysis was performed to evaluate the binding interactions between the compounds from THD and the potential targets. Based on the results, kaempferol was thus suggested as a candidate bioactive constituent. These findings contribute to a better understanding of CI pathogenesis and provide a basis for further investigations into THD.
Oxidative stress level and histopathological changes in the rat brain following separate and combined administration of cisplatin and dexamethasone.
Yavroyan ZV, Shushanyan RA, Asatryan AL … +6 more , Hakobyan NR, Hovhannisyan AG, Grigoryan AV, Abgaryan TA, Gevorgyan ES, Karapetyan AF
Brain Res · 2026 Aug · PMID 42067007 · Publisher ↗
Neurotoxicity is one of the most serious complications associated with cisplatin chemotherapy, limiting its clinical use at higher doses that may be more effective. To mitigate adverse effects caused by cisplatin-induced...
Neurotoxicity is one of the most serious complications associated with cisplatin chemotherapy, limiting its clinical use at higher doses that may be more effective. To mitigate adverse effects caused by cisplatin-induced oxidative stress, dexamethasone is often included in chemotherapy protocols due to its anti-inflammatory and immunomodulatory properties. This study aimed to identify a correlation between oxidative stress and histological changes in rat brain tissue following the single dose of intraperitoneal injection of cisplatin (8 mg/kg) and dexamethasone (4 mg/kg)in the case of separate and combined use. Biochemical analyses revealed that cisplatin and dexamethasone increased levels of malondialdehyde and decreased the activities of catalase and superoxide dismutase to varying extents after separate and combined exposure to these drugs. Histomorphological examinations showed neuronal degeneration, cytoplasmic shrinkage, and severe cytoarchitectural alterations in both hippocampal and cortical areas after separate treatments with each drug. These findings suggest that both agents exhibit pro-oxidant and neurotoxic effects. Interestingly, the combined administration of cisplatin and dexamethasone did not lead to a synergistic increase in lipid peroxidation or structural damage; instead, dexamethasone partially attenuated cisplatin-induced neurotoxicity. These findings suggest that cisplatin and dexamethasone exert their effects through different molecular mechanisms, which probably determine both the different strength of these pro-oxidant effects and the different histological changes, both individually and as a result of their combined use.
Age-related shifts in ghrelin responsiveness of dorsomedial and ventromedial hypothalamic neurons in rats.
Masliukov PM, Spirichev AA, Anfimova PA … +3 more , Moiseev KY, Salnikov EV, Pankrasheva LG
Brain Res · 2026 Aug · PMID 42055204 · Publisher ↗
The hypothalamus is a unique neuro-endocrine center that is involved in the regulation of homeostasis, vital functions, and aging. The hormone ghrelin, acting via the growth hormone secretagogue receptor 1A (GHSR-1A), af...
The hypothalamus is a unique neuro-endocrine center that is involved in the regulation of homeostasis, vital functions, and aging. The hormone ghrelin, acting via the growth hormone secretagogue receptor 1A (GHSR-1A), affects different hypothalamic nuclei, including the tuberal area, and may play an important role in the regulation of aging. The expression of GHSR-1A was studied in the dorsomedial (DMN) and ventromedial (VMN) hypothalamic nuclei of young (2 months), mature (12 months), and aged (24 months) male Wistar rats using immunohistochemistry and extracellular in vivo electrophysiology. By means of immunohistochemistry, only a small number of GHSR-1A-immunoreactive (IR) neurons were observed in the DMN (4.0 ± 1.5%) and VMN (2.3 ± 1.3%) in young rats, whereas the percentage of GHSR-1A-IR neurons significantly increased in mature (DMN - 22.1 ± 2.8%, VMN - 25.5 ± 4.4%) and aged rats (DMN - 24.8 ± 2.8%, VMN - 26.5 ± 3.8%). In all age groups, the median firing rate of DMN and VMN neurons did not change after ghrelin administration. In the DMN of young rats, ghrelin predominantly activated neurons (72%), whereas only a few neurons were inhibited by ghrelin (7%). In contrast, a large number of DMN neurons were inhibited by ghrelin in mature (50%) and aged rats (64%). In the VMN of young rats, the largest number of neurons were inhibited by ghrelin (52%), while the proportion of ghrelin-activated neurons increased, and the percentage of ghrelin-inhibited neurons decreased with aging in mature (40%) and aged rats (33%). However, shift in the responsiveness of VMN neurons to ghrelin during aging was not statistically significant. Thus, the sensitivity of hypothalamic neurons to ghrelin changes with aging, accompanied by elevation in the expression of GHS-R1A in the DMN and VMN, as well as deviations in neuronal responses to ghrelin. These alterations in hormone receptor sensitivity, along with changes in the types of responses to hormones, may contribute to the development of age-related diseases, particularly metabolic syndrome.
Physical exercise as a non-pharmacological adjunct in schizophrenia: Effects on molecular and biochemical parameters.
Cassol G, de Souza MA, Fiorin FDS
Brain Res · 2026 Aug · PMID 42044735 · Publisher ↗
Schizophrenia is a severe mental disorder affecting approximately 20 million people worldwide. It is characterized by positive symptoms (such as hallucinations and delusions) and negative symptoms (including demotivation...
Schizophrenia is a severe mental disorder affecting approximately 20 million people worldwide. It is characterized by positive symptoms (such as hallucinations and delusions) and negative symptoms (including demotivation, anhedonia, and sociality). These behavioral manifestations are associated with molecular alterations in inflammatory molecules, impaired glutamatergic and dopaminergic pathways, and disruptions in mitochondrial redox balance and neurotrophic factor levels. Antipsychotic medications are the primary treatment for managing schizophrenia symptoms; however, they often have limited efficacy on negative symptoms and can cause significant side effects. In this context, physical exercise has emerged as a promising non-pharmacological adjunctive strategy. Physical exercise has been shown to modulate peripheral and central biochemical pathways, including antioxidant and anti-inflammatory mechanisms. Additionally, it enhances neurotrophic factor expression, improves mitochondrial function, and influences glutamatergic and dopaminergic signaling. This narrative review highlights the beneficial effects of incorporating physical exercise into traditional antipsychotic treatment regimens.
PRMT5 promotes cerebral ischemia/reperfusion-induced ferroptosis via Nrf2/SLC7A11/GPX4 signaling.
Wu X, Yang Z, Zhou Y … +3 more , Jiang L, Song J, Zhao J
Brain Res · 2026 Sep · PMID 42034259 · Publisher ↗
Numerous research findings have indicated that neuronal ferroptosis is a significant pathological alteration in cerebral ischemia/reperfusion (I/R) injury, and the inhibition of this process can markedly ameliorate I/R i...
Numerous research findings have indicated that neuronal ferroptosis is a significant pathological alteration in cerebral ischemia/reperfusion (I/R) injury, and the inhibition of this process can markedly ameliorate I/R injury. Preliminary results from our research group demonstrated that the arginine methyltransferase 5 (PRMT5) protein can modulate the neuroinflammatory response and neuronal pyroptosis associated with cerebral I/R injury through the activation of the NF-κB/NLRP3 signaling pathway. In this study, we further investigate the PRMT5 role in neuronal ferroptosis regulation in cerebral I/R injury. In vitro findings demonstrated that PRMT5 knockdown led to an elevated glutathione/oxidized glutathione disulfide (GSH/GSSG) ratio and relative superoxide dismutase (SOD) activity, a reduction in malondialdehyde (MDA) levels, and an upregulation of SLC7A11 and GPX4 expression, thereby reducing neuronal ferroptosis. Conversely, PRMT5 overexpression appeared to promote neuronal ferroptosis. In addition, in vivo studies that used the PRMT5-specific inhibitor, LLY-283, confirmed that PRMT5 inhibition attenuated neuronal ferroptosis in cerebral I/R injury. Finally, the present study demonstrated that PRMT5 regulated ferroptosis through the activation of the Nrf2/SLC7A11/GPX4 signaling pathway. In conclusion, PRMT5 may be a potential therapeutic target for cerebral I/R injury.
Lentinan attenuates tau phosphorylation and memory deficits in hTau-overexpressing mice.
Li Y, Chen J
Brain Res · 2026 Aug · PMID 42025718 · Publisher ↗
BACKGROUND: Lentinan (LNT), a polysaccharide extracted from shiitake mushrooms, has been long used in Asia for improving health. Although LNT injections have been approved for cancer treatment in multiple Asian countries...
BACKGROUND: Lentinan (LNT), a polysaccharide extracted from shiitake mushrooms, has been long used in Asia for improving health. Although LNT injections have been approved for cancer treatment in multiple Asian countries, the potential of LNT in alleviating Alzheimer's disease (AD) pathology and associated cognitive impairments remains poorly understood. Thus, this study aimed to assess the neuroprotective effects of LNT. METHODS: In vitro tests were performed in HEK 293/tau cells. Moreover, to simulate AD tau pathology, human full-length tau (hTau) expression was induced using adeno-associated virus serotype 2 (AAV2) in C57/BL6 mice. Intragastric LNT administration for 1 month markedly elevated protein phosphatase 2A (PP2A) activity and decreased tau phosphorylation at Ser202/Thr205 (AT8) in AAV2-hTau infected mice. RESULTS: LNT significantly enhanced cell viability and PP2A activity while reducing tau phosphorylation in HEK 293/tau cells. Furthermore, behavioral tests demonstrated that LNT mitigated cognitive defects induced through hTau overexpression while significantly increasing the expression of synaptic protein expression such as synaptotagmin and synaptophysin. CONCLUSIONS: Our findings suggest that LNT can prevent AD-like tau hyperphosphorylation by activating PP2A and attenuate AD-like cognitive impairments by restoring synaptic plasticity and synaptogenesis. Therefore, LNT is a potential therapeutic candidate for treating tau-related diseases.
Neuroprotective and therapeutic effects of magnesium L-threonate in an amyloid β induced SH-SY5Y cell model of Alzheimer's disease.
Sis CO, Yildiz O, Elci MP … +2 more , Fatsa T, Oren S
Brain Res · 2026 Aug · PMID 42025717 · Publisher ↗
Abstract loading — click title to view on PubMed.
Microglial inhibition in the basolateral amygdala is associated with improved socio-emotional behaviors following sleep deprivation in mice.
Xin T, Kong D, Shi M … +7 more , Wei C, Chen G, Wang S, Zhao S, Ma Y, Jin X, Liu Z
Brain Res · 2026 Aug · PMID 42009179 · Publisher ↗
Sleep deprivation (SD) is associated with impairments in emotional regulation and social behavior, potentially involving neuroinflammatory mechanisms. Microglia, as key regulators of neuroinflammation, have been implicat...
Sleep deprivation (SD) is associated with impairments in emotional regulation and social behavior, potentially involving neuroinflammatory mechanisms. Microglia, as key regulators of neuroinflammation, have been implicated in neuropsychiatric disorders; however, their role in specific brain regions underlying SD-induced behavioral changes remains unclear. In this study, we investigated the contribution of microglia in the basolateral amygdala (BLA) to SD-induced behavioral alterations in mice. Using chemogenetic approaches, we bidirectionally manipulated microglial activity and assessed anxiety-like behavior and social interaction. We further examined associated changes in inflammatory markers, synaptic proteins, mitochondrial function, and autophagy. We found that SD induced anxiety-like behavior and social deficits, accompanied by increased inflammatory signaling and cellular stress markers in the amygdala. Chemogenetic inhibition of BLA microglia was associated with improvements in both anxiety-like and social behaviors, whereas activation produced more limited and task-dependent effects. Microglial inhibition was also associated with reduced inflammatory markers and partial normalization of synaptic, mitochondrial, and autophagy-related changes. In contrast, global microglial depletion did not rescue behavioral deficits. These findings suggest that microglial activity in the BLA is associated with the regulation of socio-emotional behaviors following SD. The observed behavioral effects may involve coordinated changes in neuroinflammation and cellular stress-related processes.
The emergence of the modern human Mind: Inner speech and its link to memory mechanisms.
Parada-Palma J, Álamos-Grau F, Henríquez-Ch R … +1 more , Aboitiz F
Brain Res · 2026 Aug · PMID 42009178 · Publisher ↗
Inner speech (IS) is considered a unique feature of the human brain and an important component of mental life in many individuals, although it is not uniformly experienced across people.. The dysregulation of IS, in term...
Inner speech (IS) is considered a unique feature of the human brain and an important component of mental life in many individuals, although it is not uniformly experienced across people.. The dysregulation of IS, in terms of its frequency, contents, or self-monitoring, has been linked to distinct neuropsychiatric conditions. In the child, more complex forms of IS usually develop around 7 years of age, when language is already well developed. While this phenomenon has usually been attributed to the maturation of verbal working memory circuits, this view does not account for the rich mental experiences and remembrances that accompany this phenomenon, which were highlighted by Lev Vygotsky's foundational studies. Addressing this issue, we propose that IS involves an engagement of two main neuronal processes: working memory capacity (especially verbal) and memory recall mechanisms, partly dependent on hippocampal function. While these two processes have long been considered as relatively separate phenomena, we will argue that there is a tight connection between working memory and episodic and semantic memory, and that this link was exploited in the human brain to amplify internal narratives, largely through the use of IS, providing structure to the human mind.
Cajanine alleviates anxiety and fear extinction deficits in female mice exposed to single prolonged stress via the ERβ/NF-κB pathway.
Jiang L, Zhang Y, Yan Q … +1 more , Song Y
Brain Res · 2026 Aug · PMID 42009177 · Publisher ↗
BACKGROUND: Currently, post-traumatic stress disorder (PTSD) lacks effective treatment strategies. Cajanine has been shown to ameliorate neuroinflammation-related diseases via diverse neuroprotective pathways, indicating...
BACKGROUND: Currently, post-traumatic stress disorder (PTSD) lacks effective treatment strategies. Cajanine has been shown to ameliorate neuroinflammation-related diseases via diverse neuroprotective pathways, indicating its therapeutic potential role for PTSD. OBJECTIVES: This study aimed to explore the effects of cajanine on PTSD and investigate the underlying mechanisms. METHODS: A single prolonged stress (SPS) mouse model was established in mice by conducting psychological, physiological, and chemical stress to mimic PTSD. Cajanine was administered to mice via oral gavage at two doses of 20 and 60 mg/kg. Behavioral assessments included the marble-burying test (MBT), elevated plus maze test (EPMT), and fear memory extinction test (FMET). Expressions of estrogen receptors (ERs) and inflammatory factors in the hippocampus, frontal cortex, and amygdala were quantified via enzyme-linked immunosorbent assay (ELISA) and biochemical assay. RESULTS: SPS induced anxiety-like behaviors and fear memory extinction deficits, along with increased NF-κB, IL-6, and TNF-α expression in the hippocampus, frontal cortex, and amygdala of both the male and female mice. In addition, SPS triggered a reduction in ERβ expression in the hippocampus, frontal cortex, and amygdala of the female mice. Cajanine (60 mg/kg) alleviated the behavioral abnormalities and normalized the overexpression of neuroinflammatory factors and the reduced ERβ level in these brain regions, and this effect was observed only in female SPS mice. Coadministration of cajanine with an ERβ antagonist reversed the beneficial effects of cajanine. of cajanine. CONCLUSION: Cajanine alleviates SPS-induced behavioral deficits in female mice by exerting anti-neuroinflammation effects via ERβ/NF-κB pathway in the hippocampus, cerebral cortex, and amygdala.
Linguistic-visual routines and name activation in visual world studies of spoken word recognition.
Pontillo DF, Spivey MJ, Tanenhaus MK
Brain Res · 2026 Aug · PMID 42001990 · Publisher ↗
We address a longstanding issue in visual world studies of speech and spoken word recognition: What role does retrieval of object names play in mediating eye movements to displayed objects? We propose a novel "linguistic...
We address a longstanding issue in visual world studies of speech and spoken word recognition: What role does retrieval of object names play in mediating eye movements to displayed objects? We propose a novel "linguistic-visual routines" linking hypothesis in which the representations of spoken words are linked to schematic visual representations and visuomotor routines, without involvement of object names. When triggered during reference resolution, these routines direct gaze to objects in a co-present visual world that are consistent with the schematic visual representations. To evaluate possible picture-naming in this task, we created materials that included "synonym" objects (e.g., a picture of an object that could be named as either "couch" or "sofa", where norms established that each name was an equally good fit for the object, but one name was dominant, in this case, "couch". Name typicality effects were used to diagnose if and when object names affect eye movements, using targets that were cohorts of either the dominant or subordinate name of a competitor. We reasoned that if names were retrieved, then there would be larger cohort effects and delayed looks to targets when the target was a cohort of the dominant name. We ran conceptual simulations using normalized recurrence localist attractor networks, illustrating predicted data patterns for models where: (1) object names do not affect fixations; (2) retrieval of object names mediates fixations, and (3) sub-threshold priming of object names weakly affects eye-movements. Experiment 1 used a standard Visual World design, finding minimal evidence, if any, for effects of name typicality. In Experiments 2 and 3, participants were cued that a particular object would be occluded before the instruction begins and thus were likely to retrieve the object name to help maintain it in memory. On critical trials, synonym objects were occluded in Experiment 2, and distractor objects were occluded in Experiment 3. Simulations were again used to illustrate predicted data patterns, namely name-retrieval effects only when the synonym object was occluded. In Experiment 2, where the synonym object was occluded, there were strong name typicality effects, with larger cohort effects and delayed target looks for the dominant name, matching the predictions of the model with name retrieval. In Experiment 3, where a distractor object was occluded, cohort effects were not affected by name typicality. We then introduce models simulating conditions from a pilot study in which visually drawing attention to an object, but not occluding it, also does not result in name typicality effects. Taken together, the results are clearly consistent with the linguistic-visual routines hypothesis and inconsistent with name retrieval. We conclude that object name representations play at most a minimal role in mediating fixations in Visual World experiments of spoken word recognition.
Task-specific cortical modulation induced by Tai Chi during postural control in older adults with diabetic peripheral neuropathy: An fNIRS study.
Duan X, Wang X, Song Q … +2 more , Yin Z, Mao D
Brain Res · 2026 Aug · PMID 42001989 · Publisher ↗
Diabetic peripheral neuropathy (DPN) significantly impairs postural control in older adults. While Tai Chi (TC) improves postural stability in this population, the underlying neural mechanisms remain incompletely underst...
Diabetic peripheral neuropathy (DPN) significantly impairs postural control in older adults. While Tai Chi (TC) improves postural stability in this population, the underlying neural mechanisms remain incompletely understood. This study examined whether TC alters task-evoked cortical activation during static and dynamic postural control in older adults with DPN and whether neural changes are associated with functional improvements. Forty older adults with DPN were stratified by DPN scores and randomly allocated to two groups. The TC group received supervised TC training, while the control group attended health education sessions for 8 weeks. Functional near-infrared spectroscopy (fNIRS) was used to measure changes in hemodynamic responses in the premotor cortex and supplementary motor area (PMC/SMA), primary motor cortex (M1), primary somatosensory cortex (S1), and somatosensory association cortex (SAC) during postural control tasks. After Bonferroni-adjusted post hoc testing, the TC group exhibited reduced PMC/SMA and M1 activation during the static task and increased M1 and S1 activation during the dynamic task compared with baseline. Correspondingly, the TC group showed reduced static sway (COP-RMS and A95) and improved TUG performance. In correlation analyses with Benjamini-Hochberg FDR correction, changes in PMC/SMA and SAC activation were positively associated with changes in A95 during static postural control. In contrast, no significant correlations were found between cortical activation changes and TUG performance during dynamic postural control. These findings suggest that TC modulates cortical activation in a task-specific way and improves postural control in older adults with DPN through distinct neural mechanisms.
MFSD2A as a prognostic biomarker in low-grade glioma: mechanistic links to immune suppression.
Jia Z, Jiang T, Zhang Y … +6 more , Chen Q, Cen X, Yuan Q, Di Z, Ma C, Lin X
Brain Res · 2026 Aug · PMID 42001988 · Publisher ↗
This study investigates the role of major facilitator superfamily domain containing 2A (MFSD2A) in low-grade glioma (LGG) progression, focusing on its association with tumor immune infiltration and patient survival. Usin...
This study investigates the role of major facilitator superfamily domain containing 2A (MFSD2A) in low-grade glioma (LGG) progression, focusing on its association with tumor immune infiltration and patient survival. Using GTEx (normal tissues) and TCGA (LGG) datasets, we observed elevated MFSD2A mRNA levels in LGG versus normal brain tissue. Kaplan-Meier and multivariate Cox analyses revealed that low MFSD2A expression correlated with improved overall survival (OS) and disease-specific survival (DSS), independent of clinicopathological factors (WHO grade, IDH status, 1p/19q codeletion, etc.). DNA methylation analysis further supported its prognostic value. Gene enrichment (GSEA) showed high MFSD2A expression enriched in immune/cytokine pathways, while low expression linked to neural signaling. Network analyses of protein interactomes identified MFSD2A as a key node exhibiting inverse associations with certain lymphoid subpopulations. Correlation analyses revealed that MFSD2A expression was positively associated with blood-brain barrier integrity, angiogenesis, and select immune checkpoint pathways. This transporter protein demonstrated significant enrichment in pathways characteristic of the tumor stromal niche. These results establish MFSD2A as an immunological determinant in LGG pathogenesis, providing mechanistic insights into its prognostic and therapeutic relevance.
Preventive effects of pomegranate seed oil on transient middle cerebral artery occlusion via the Keap1/Nrf2/NQO1 pathway in the rats cortex.
Li D, Zhang C, Luo Q … +5 more , Li M, Tian M, Jiao H, Xi X, Weng Q
Brain Res · 2026 Aug · PMID 42000414 · Publisher ↗
Ischemic stroke remains a pressing challenge that needs to be solved. Energy metabolic failure is a critical factor contributing to mitochondrial dysfunction and oxidative stress in the pathogenesis of brain ischemia, le...
Ischemic stroke remains a pressing challenge that needs to be solved. Energy metabolic failure is a critical factor contributing to mitochondrial dysfunction and oxidative stress in the pathogenesis of brain ischemia, leading to the generation of excessive reactive oxygen species. Pomegranate seed oil (PSO) exhibits antioxidant properties; however, its protective effects against cerebral ischemia/reperfusion injury and the underlying mechanisms remain unclear. In this study, a transient middle cerebral artery occlusion (tMCAO) rat model was employed to simulate cerebral ischemia/reperfusion injury. We investigated the mechanisms by which different concentrations of PSO modulate oxidative damage caused by cerebral ischemia/reperfusion injury through the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/NAD(P)H quinone oxidoreductase 1 (NQO1) pathway in cortex. SD male rats were randomly divided into four groups: Control, tMCAO + 0.9% sodium chloride (NaCl), tMCAO + LO (low concentration of PSO), tMCAO + MO (medium concentration of PSO), and tMCAO + HO (high concentration of PSO). Our findings suggest that low concentration of PSO exerts neuroprotective effects by activating Nrf2 and NQO1, thereby reducing oxidative stress. Furthermore, LO significantly improved neurological scores and reduced neuronal damage by Hematoxylin and Eosin (HE) staining and Transmission Electron Microscopy. Additionally, the results demonstrated an increase in superoxide dismutase enzyme activities and catalase, and a decrease in malondialdehyde and lactate dehydrogenase levels. In contrast, MO and HO exhibited suboptimal effects. To sum up, these results indicate that PSO activates neuroprotective pathways against oxidative stress following cerebral ischemia/reperfusion injury via the Keap1/Nrf2/NQO1 pathway, providing novel insights into potential preventive therapies for cerebral ischemia/reperfusion.
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