Neurosci. Lett. [JOURNAL]
Sun
200 papers
Proteomic profiling of the prefrontal cortex reveals Dysregulated Mitochondria-Metabolism-Synapse axis in a chronic Stress-Induced mouse model of depression.
Zhang Y, Li L, Zhang X … +4 more , Xu J, Kan W, Wang T, Du J
Neurosci Lett · 2026 Apr · PMID 41765126 · Publisher ↗
Major depressive disorder (MDD) is a highly prevalent and disabling neuropsychiatric condition, its underlying molecular mechanisms remain incompletely understood. This study aimed to systematically characterize proteomi...
Major depressive disorder (MDD) is a highly prevalent and disabling neuropsychiatric condition, its underlying molecular mechanisms remain incompletely understood. This study aimed to systematically characterize proteomic alterations in the prefrontal cortex associated with depression-like behaviors induced by chronic stress. Depression-like behaviors in mice were evaluated using standardized behavioral tests and confirmed by Digital Western blotting. Quantitative proteomic analysis of prefrontal cortex tissues was performed to compare chronic social defeat stress (CSDS) and control groups, identifying differentially expressed proteins (DEPs). These DEPs were subsequently subjected to bioinformatic analyses, including Gene Ontology (GO) enrichment and construction of protein-protein interaction (PPI) networks. Key DEPs were further validated by parallel reaction monitoring (PRM) and Western blotting. We found that CSDS mice displayed robust depression-like phenotypes, including decreased sucrose preference and increased immobility. Western blot analysis confirmed the dysregulation of ER stress markers, proinflammatory factors, and proteins related to synaptic plasticity. Proteomic analysis identified 95 differentially expressed proteins, with GO enrichment revealing predominant associations with gene regulation, mitochondrial, metabolic, and synaptic function. PPI network analysis highlighted hub proteins involved in mitochondrial, endoplasmic reticulum, and synaptic regulation. PRM and Western blot validation confirmed dysregulation in four functional modules: 1) Mitochondrial function (Mrpl17, Mrpl41)；2) Signal transduction (Rigi, Pbrm1, Plppr5, Glyr1)；3) Metabolic regulation(Pmvk, Rpl13a, Ubtd2, Tmem63b)；4) Synaptic plasticity (Kif21b, Klc4, Lama2, Col4a2). Our results demonstrate that chronic stress disrupts prefrontal cortical pathways that govern gene regulation, mitochondrial metabolism, and synaptic function, suggesting their concerted contribution to the pathophysiology of depression.
Inhibition of the NF-κB/STAT3 pathway to reduce spinal microglia activation: a mechanism by which manual acupuncture alleviates rheumatoid arthritis.
Zhang Q, Wang Y
Neurosci Lett · 2026 Apr · PMID 41763350 · Publisher ↗
BACKGROUND: Rheumatoid arthritis (RA) discomfort is linked to spinal cord microglia activation. Manual acupuncture (MA, twirling manipulation) reduces RA pain. MA's ability to relieve RA discomfort was examined in this s...
BACKGROUND: Rheumatoid arthritis (RA) discomfort is linked to spinal cord microglia activation. Manual acupuncture (MA, twirling manipulation) reduces RA pain. MA's ability to relieve RA discomfort was examined in this study. METHODS: After receiving complete Freund's adjuvant (CFA), RA rats received acupuncture (with or without twisting manipulation). Paw withdrawal latency (PWL), nociceptive threshold, and hematoxylin and eosin (H&E) staining assessed arthritis severity. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the levels of inflammatory factors (IL-1β, TNF-α and IL-6) in the spinal dorsal horn. Immunofluorescence was used to assess the expression of p-p38 and Iba-1 in the ipsilateral hippocampus and ipsilateral (right) dorsal root ganglia (DRG). Western blot was used to evaluate the expression of proteins linked to the nuclear factor kappa-B (NF-κB) /signal transducer and activator of transcription 3 (STAT3) pathway. RESULTS: MA treatment enhanced PWL, inhibited the expression of spinal dorsal horn inflammatory factor and the activation of ipsilateral DRG or ipsilateral hippocampal microglia, also down-regulated NF-κB/STAT3 pathway proteins. The effect of MA on RA symptoms was better than acupuncture alone. CONCLUSIONS: Our findings demonstrate that MA significantly ameliorates pain in CFA-induced RA rats. The novelty of this study lies in identifying that this analgesic effect is achieved through the inhibition of the NF-κB/STAT3 signaling pathway, leading to a marked reduction in spinal microglia activation.
Selective upregulation of fatty acid-binding protein 5 within the basolateral amygdala blunts stress-induced reinstatement of cocaine-seeking behavior in mice.
Roeder N, Powell A, Hamilton J … +6 more , Richardson B, Sharma A, Sharafshah A, Blum K, Pinhasov A, Thanos PK
Neurosci Lett · 2026 May · PMID 41730471 · Publisher ↗
Anandamide (AEA), an endogenous cannabinoid, is thought to exert an inhibitory role in the basolateral amygdala complex (BLA), dampening hypothalamus-pituitary-adrenal (HPA) axis activation and reducing stress-related fe...
Anandamide (AEA), an endogenous cannabinoid, is thought to exert an inhibitory role in the basolateral amygdala complex (BLA), dampening hypothalamus-pituitary-adrenal (HPA) axis activation and reducing stress-related fear and anxiety behaviors. Stress-induced reductions in AEA mediated signaling have been associated with amygdala hyperexcitability contributing to the reinstatement of cocaine-seeking behavior. Fatty acid-binding protein 5 (FABP5) serves as the major intracellular transporter of AEA, facilitating its degradation by fatty acid amide hydrolase (FAAH). In vivo studies demonstrate that FABP5 enhances AEA uptake and hydrolysis. Given the established role of AEA signaling in modulating stress reactivity through the amygdala, changes in FABP5 expression may influence drug seeking in response to stressful stimuli. In the current study we investigated the behavioral impact of viral vector induced FABP5 overexpression in the BLA. Male C57BL/6N mice received a bilateral intracranial injection into the BLA with either an AAV5-GFP control virus or an AAV5-FABP5 construct. Following transfection, mice were assessed for cocaine-seeking behavior using the conditioned place preference (CPP) paradigm. In addition, mice were assessed for a stress-induced reinstatement of cocaine CPP. Surprisingly, upregulation of FABP5 in the BLA was found to reduce stress-induced reinstatement of cocaine-seeking behavior. These findings mirror previous observations of FAAH overexpression in the BLA and suggest a complex role of FABP5 in regulation of stress responses, potentially via modulation of GABAergic and glutamatergic neurotransmission. Further work is warranted to elucidate the mechanisms by which FABP5 influences stress reactivity and reward-related behaviors through its modulation of endocannabinoid signaling in the BLA.
Pentosidine accumulation induced by Akr1a deficiency drives aggression and hyperactivity.
Iino K, Toriumi K, Miyashita M … +7 more , Suzuki K, Tabata K, Miyata S, Takahashi M, Fujii J, Itokawa M, Arai M
Neurosci Lett · 2026 Apr · PMID 41730470 · Publisher ↗
Advanced glycation end products (AGEs) are a heterogeneous group of glycation-derived compounds that accumulate under metabolic stress and contribute to age-related and chronic diseases. Pentosidine (PEN), a well-charact...
Advanced glycation end products (AGEs) are a heterogeneous group of glycation-derived compounds that accumulate under metabolic stress and contribute to age-related and chronic diseases. Pentosidine (PEN), a well-characterized fluorescent AGE, increases during aging under certain pathological conditions. In particular, increased PEN levels have been observed in a subset of patients with schizophrenia and are associated with more severe clinical outcomes. Glucuronic acid (GlcA) has previously been identified as a metabolic precursor of PEN, and impaired GlcA metabolism due to reduced aldo-keto reductase family 1 member A1 (AKR1A1) activity may underlie PEN accumulation. In the present study, to investigate the neurobiological impact of endogenous PEN accumulation, we examined neurobehavioral consequences using Akr1a knockout (KO) mice, which exhibit impaired GlcA metabolism. These mice exhibited significantly elevated PEN levels in both the plasma and prefrontal cortex (Pfc), a brain region critically involved in higher-order cognitive and behavioral regulation, accompanied by increased aggression and hyperactivity-behavioral domains relevant to patients with schizophrenia. Notably, aggression measures were positively correlated with PEN concentrations, whereas PEN levels were associated with novelty-driven exploratory locomotion but not with sustained baseline locomotor activity. Transcriptomic analysis of Pfc revealed altered expression of genes involved in guanylate cyclase signaling, cytoskeletal organization, and the immune response. Cyclic guanosine monophosphate (cGMP) levels were significantly reduced, suggesting impaired downstream signaling. Together, these findings demonstrate that GlcA-driven PEN accumulation induces molecular and behavioral alterations in the brain and provides a dimensional mouse model linking glycation-related metabolic stress to aggression and hyperactivity relevant to schizophrenia.
Activation of taf7l promotes sensory nerve regeneration by enhancing conditioning effect.
Sugiura K, Omura T, Wang J … +2 more , Latremoliere A, Matsuyama Y
Neurosci Lett · 2026 Apr · PMID 41730469 · Publisher ↗
Peripheral nervous system (PNS) neurons can regenerate after injury, yet functional recovery is often limited, especially following proximal lesions or delayed repair. Preconditioning nerve injury accelerates axonal grow...
Peripheral nervous system (PNS) neurons can regenerate after injury, yet functional recovery is often limited, especially following proximal lesions or delayed repair. Preconditioning nerve injury accelerates axonal growth by inducing regeneration associated genes (RAGs). To identify novel growth regulators, we screened nine genetically diverse Collaborative Cross (CC) mouse strains for strain-dependent differences in dorsal root ganglion (DRG) neurite outgrowth on Matrigel. All strains exhibited a ≥ 2-fold preconditioning effect, with DBA/2J showing the most pronounced growth. Genome-wide expression profiling revealed Taf7l as the transcript most strongly correlated with neurite outgrowth. Immunohistochemistry demonstrated Taf7l localization in DRG neurons, with expression enhanced after preconditioning. Quantitative RT-PCR showed a progressive post-injury increase in Taf7l mRNA, reaching > 5-fold by day 14. Functional studies using lentiviral vectors showed that Taf7l knockdown reduced neurite length by 27% without affecting initiation rate, while Taf7l overexpression significantly increased both initiation rate and axonal length. These findings identify Taf7l, previously known for roles in spermatogenesis and adipogenesis, as a novel transcriptional regulator in neurons. Taf7l is induced by nerve injury and modulates neurite outgrowth, suggesting it as a potential therapeutic target to enhance PNS regenerative capacity.
Corrigendum to "TMEM119-positive microglia were increased in the brains of patients with amyotrophic lateral sclerosis" [Neurosci. Lett. 833 (2024) 137829].
Togawa N, Ayaki T, Yoshii D … +3 more , Maki T, Sawamoto N, Takahashi R
Neurosci Lett · 2026 Mar · PMID 41723070 · Publisher ↗
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Inhibition of Death-Associated Protein Kinase 1 ameliorates central and peripheral pathological changes in a mouse model of Parkinson's disease.
Li Z, Chen Z, Duan Z … +4 more , Liu Y, Gong A, Han W, Rong L
Neurosci Lett · 2026 Apr · PMID 41722891 · Publisher ↗
BACKGROUND: Parkinson's disease (PD) is a multisystem neurodegenerative disorder affecting both the central nervous system (CNS) and the enteric nervous system (ENS). Growing evidence implicates gut-brain axis dysfunctio...
BACKGROUND: Parkinson's disease (PD) is a multisystem neurodegenerative disorder affecting both the central nervous system (CNS) and the enteric nervous system (ENS). Growing evidence implicates gut-brain axis dysfunction and pathological α-synuclein (α-syn) aggregation as pivotal drivers of PD pathogenesis. Death-Associated Protein Kinase 1 (DAPK1), a pro-apoptotic serine/threonine kinase known to promote neurodegeneration and α-syn phosphorylation. yet its specific role in gut-brain axis pathology.remains unexplored. This study therefore aimed to (1) map DAPK1 expression dynamics along the gut-brain axis in PD mice, and (2) evaluate the therapeutic efficacy of DAPK1 inhibition on central/peripheral pathology. METHODS: MPTP-induced PD was modeled in C57BL/6 mice by intraperitoneal MPTP injection. Mice were stratified into: Control, MPTP, and MPTP + DAPK1 inhibitor(TC-DAPK6) groups. DAPK1 and α-syn expression in substantia nigra, stomach, small intestine, and colon were quantified by Western blot (WB) and immunohistochemistry (IHC). Histopathological alterations were assessed via H&E staining. with mucosal inflammation severity scored by Chiu score for small intestinal mucosal injury and the Geboes score for colonic mucosal injury. RESULTS: MPTP mice exhibited significant upregulation of DAPK1 and α-syn protein levels in all examined CNS and ENS tissues vs. Controls.Concomitantly, H&E staining revealed severe inflammatory damage in the small intestine and colon,validated by elevated Chiu/Geboes scores. DAPK1 inhibitor treatment: Normalized DAPK1/α-syn expression across all tissues to near-control levels;Significantly reduced intestinal inflammation, as indicated by a decline in the Chiu score in the small intestine and a decline in the Geboes score in the colon. CONCLUSION: DAPK1 drives multisystem pathology along the gut-brain axis in PD, where its overexpression promotes α-syn accumulation and intestinal inflammation. Pharmacological DAPK1 inhibition concurrently ameliorates CNS and ENS pathology,establishing it as a promising disease-modifying target for holistic PD intervention.
Target epigenetics mechanism to prevent synaptic dysfunction of adult amblyopia.
Ding S, Li Y, Cao Q … +3 more , Zhang T, Li S, Li L
Neurosci Lett · 2026 Apr · PMID 41720389 · Publisher ↗
Amblyopia is a neurodevelopmental disorder, and there are no effective treatment methods for adult amblyopia patients due to the decline in synaptic plasticity in visual cortex. Enriched environment (EE) has been shown t...
Amblyopia is a neurodevelopmental disorder, and there are no effective treatment methods for adult amblyopia patients due to the decline in synaptic plasticity in visual cortex. Enriched environment (EE) has been shown to enhance synaptic plasticity, which is mediated, at least in part, by epigenetic mechanisms involving histone acetylation. This study aims to investigate whether histone deacetylase (HDAC) inhibitors can replicate the effects of EE on visual cortical plasticity, thereby offering novel therapeutic insights for adult amblyopia. First, we established adult amblyopia mice model, which were then randomized into five groups: untreated amblyopia, standard housing, EE, vehicle, trichostatin A (TSA) groups, with normal mice serving as controls. To evaluate synaptic plasticity in visual cortex, we measured synaptic marker VGLUT2, synaptic ultrastructure and long-term potentiation (LTP). Additionally, biochemical analyses were conducted to measure alterations of HDACs associated with synaptic integrity. Our findings revealed that EE enhanced synaptic plasticity in visual cortex of adult amblyopia mice and was associated with reduced HDAC3 expression. Similarly, the broad HDAC inhibitor TSA, improved synaptic ultrastructure, increased VGLUT2 expression, and potentiated LTP, functionally resembling several key effects of EE. Importantly, TSA targets multiple HDAC isoforms, and the observed reduction in HDAC3 levels is correlated with, but does not establish, a causal role for HDAC3. These results indicate that broad HDAC inhibition can mimic EE-induced plasticity in adult amblyopia, while highlighting the need for selective HDAC3-targeted approaches to determine mechanistic specificity. Overall, our study provides a foundation for developing epigenetic-based strategies to enhance adult visual cortical plasticity.
Hydrogen sulfide protects dopaminergic neurons via NLRP3 inflammasome inhibition in an MPTP mouse model of Parkinson's disease.
Liu KT, Shui Y, Hong J … +3 more , Xiao L, He Z, Xiao L
Neurosci Lett · 2026 Apr · PMID 41707904 · Publisher ↗
BACKGROUND: Hydrogen sulfide (HS) has emerged as a potential neuroprotective agent in neurodegenerative diseases, including Parkinson's disease (PD). However, its role in regulating neuroinflammation through the NLRP3 in...
BACKGROUND: Hydrogen sulfide (HS) has emerged as a potential neuroprotective agent in neurodegenerative diseases, including Parkinson's disease (PD). However, its role in regulating neuroinflammation through the NLRP3 inflammasome remains unclear. METHODS: We established a PD mouse model using MPTP (30 mg/kg, i.p. for 5 days) and administered NaHS (an HS donor, 5.6 mg/kg, i.p.) daily during the same period. Behavioral tests, immunohistochemistry, and Western blotting were used to assess motor function, dopaminergic neuron survival, NLRP3 inflammasome activation, and inflammatory cytokine levels. RESULTS: NaHS significantly improved motor deficits and preserved tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. It markedly suppressed the expression of NLRP3, ASC, cleaved caspase-1, and IL-1β, indicating inhibition of inflammasome activation. CONCLUSION: Exogenous HS protects dopaminergic neurons in MPTP-induced PD mice, likely by suppressing NLRP3 inflammasome activation, suggesting its therapeutic potential for PD.
Default mode network connectivity is associated with executive and language performance in mild cognitive impairment.
Nasiri H, Mohammadtaheri B, Khosravi F … +11 more , Ghadiminia N, Saberian P, Mohammadian M, Shakeri S, Hendudari F, Siyah Rood YK, Hassanpoor A, Sadat S, Bagheri F, Mayeli M, Alzheimer’s Disease Neuroimaging Initiative
Neurosci Lett · 2026 Apr · PMID 41707903 · Publisher ↗
Disruptions in default mode network (DMN) connectivity are well documented in Alzheimer's disease (AD), yet their associations with specific cognitive domains remain unclear. This study examined relationships between ant...
Disruptions in default mode network (DMN) connectivity are well documented in Alzheimer's disease (AD), yet their associations with specific cognitive domains remain unclear. This study examined relationships between anterior and posterior DMN functional connectivity and memory, executive function, and language performance across the AD continuum. We conducted a cross-sectional analysis of resting-state fMRI and composite cognitive scores from 154 participants (61 cognitively normal, 68 mild cognitive impairment [MCI], and 25 AD). DMN connectivity metrics were derived from regional voxelwise correlations within anterior (aDMN) and posterior (pDMN) subdivisions. Associations between DMN measures and cognitive domains were assessed using multiple linear regression adjusted for age, sex, and years of education, with correction for multiple comparisons. No DMN measure was significantly associated with memory performance in any diagnostic group after correction. In the MCI group, executive and language performance were associated with anterior-posterior DMN connectivity, with weaker coupling linked to poorer performance across these domains. No significant DMN-cognition associations were observed in the cognitively normal or AD groups. After additional adjustment for white matter hyperintensities, only anterior-posterior DMN connectivity remained significantly associated with executive and language performance in the MCI group. Overall, DMN connectivity-cognition relationships were domain-specific and most evident in MCI, supporting the concept of a transitional stage in which network-level functional organization is related to cognitive performance.
Corrigendum to "mGluR5 regulates inflammatory pain and pain aversion of CFA mice by mediating ERK/PI3K signaling pathway". [Neurosci. Lett. May 29 (2025) 859-861:138281].
Tianxin Z, Zhongyu H, Weishan Z … +6 more , Can W, Jiahong L, Shuhan W, Runheng Z, Chang Z, Yuxin M
Neurosci Lett · 2026 Mar · PMID 41702801 · Publisher ↗
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Human microglia express anti-inflammatory ISG15 in response to Neisseria meningitidis.
Dunphy AM, Majithia K, Krueger QA … +2 more , Johnson MB, Marriott I
Neurosci Lett · 2026 Mar · PMID 41688008 · Publisher ↗
Glial cells respond to the presence of bacteria by producing inflammatory mediators but these responses can result in damage to the central nervous system (CNS). However, glia can also produce immunosuppressive mediators...
Glial cells respond to the presence of bacteria by producing inflammatory mediators but these responses can result in damage to the central nervous system (CNS). However, glia can also produce immunosuppressive mediators that can serve to mitigate such effects. Here, we demonstrate that human microglial cells and, to a lesser extent, primary human astrocytes, can express and secrete interferon stimulated gene 15 (ISG15) in response to a clinically relevant CNS pathogen, Neisseria meningitidis, and ligands for Toll-like receptor 4 (TLR4) that include lipopolysaccharide and lipooligosaccharide derived from N. meningitidis. Exogenous ISG15 failed to elicit human neutrophil-like cell migration and induce or augment their inflammatory responses. Similarly, recombinant ISG15 application did not elicit inflammatory cytokine or chemokine production by either human microglial cells or astrocytes, and did not augment their responses to TLR stimulation or N. meningitidis infection. Rather, ISG15 treatment limited N. meningitidis-induced NF-κB activation and associated inflammatory cytokine production by these cells, perhaps via a non-canonical TLR-mediated pathway. These observations may be indictive of a novel negative feedback loop whereby the recognition of bacterial motifs precipitates ISG15 expression by resident microglia that subsequently mitigates further neuroinflammatory responses.
Comparative analysis of BORIS, Ethovision, DeepLabCut, and SimBA for quantifying autism spectrum disorder-like behaviors in the valproic acid mouse model.
Bouargane Z, Olucha-Bordonau FE, Bennis M … +2 more , Ba-M'hamed S, Lamghari-Moubarrad FZ
Neurosci Lett · 2026 Mar · PMID 41679592 · Publisher ↗
Preclinical research often relies on animal observation and subsequent behavioral analysis to study brain function; however, traditional methods are considered time-consuming and prone to human error. In contrast, emergi...
Preclinical research often relies on animal observation and subsequent behavioral analysis to study brain function; however, traditional methods are considered time-consuming and prone to human error. In contrast, emerging machine learning (ML) approaches now enable rapid, objective, and high-resolution behavioral assessment, such as DeepLabCut (DLC), combined with post-processing tools like Simple Behavioral Analysis (SimBA), which allow high-resolution behavioral classification. DLC provides accurate markerless tracking, while SimBA improves sensitivity and reliability in behavior identification. This study tests the hypothesis that pose-estimation-based behavioral analysis increases sensitivity for detecting functionally relevant impairments in social investigation and motor pattern organization in the valproic acid (VPA) mouse model of ASD, compared with conventional semi-automated tracking (Ethovision) and manual scoring (BORIS). Our results revealed significant and consistent core ASD-like symptoms in VPA-exposed mice across all methods. In the 3-chamber test, the tracking of the animal's nose provided greater precision and accuracy in detecting sociability deficits in VPA-exposed mice compared to the Ethovision analysis method. Correlation and Bland-Altman analyses indicated moderate agreement between both approaches for chamber time, but low concordance for the time in the proximity of the cages. Additionally, VPA-exposed mice exhibited significantly more repetitive behaviors (self-grooming and rearing) across both scoring methods. Indeed, DLC and BORIS scoring results demonstrated a higher correlation coefficient and a lower bias in the Bland-Altman analysis. Overall, this study demonstrates that integrating DLC and SimBA enhances behavioral scoring precision, overcomes limitations of conventional methods, and surpasses commercial automated tracking systems in detecting ASD-like phenotypes in mice.
Chemogenetic regulation of direct and indirect pathway neurons in the dorsomedial striatum reshapes cocaine-induced conditioned place preference behaviors in mice.
Chen K, Qiao H, Zuo Y … +8 more , Zhao X, Wang J, Zhang J, Zhang Y, Yang X, Wu Y, Gao K, Diao Z
Neurosci Lett · 2026 Apr · PMID 41672397 · Publisher ↗
The rewarding properties of cocaine generate potent and long-lasting associations with environmental cues through altering neuronal properties, underlying reinforced drug-taking and seeking behaviors. Disrupting these as...
The rewarding properties of cocaine generate potent and long-lasting associations with environmental cues through altering neuronal properties, underlying reinforced drug-taking and seeking behaviors. Disrupting these associations could reduce cravings and forestall relapse. The dorsomedial striatum (DMS) is implicated in reward processing and goal-directed behaviors, yet its specific role in modulating cocaine-associated contextual memory remains poorly defined. To elucidate DMS's role in cue-induced memory retrieval, multifaceted approaches were employed in male mice, including the conditioned place preference (CPP) model, behavioral assessments, c-Fos immunostaining, and chemogenetic methods. Our findings demonstrate that following a four-day conditioning period, cocaine-conditioned mice re-exposed to the CPP context exhibited increased c-Fos cells in the DMS, positively correlating with CPP scores. Contrary to the classical antagonistic model, chemogenetic activation of either D2 receptor- (D2-MSNs) or D1 receptor-expressing MSNs (D1-MSNs) in the DMS significantly disrupted drug-context associations and reduced acquired preference, whereas inhibition enhanced CPP behaviors. These findings demonstrate the DMS as a critical node for mediating drug-context memory retrieval, providing novel insights into the functional roles of D1- and D2-MSNs in this process. Regulating the activity of DMS neurons may be a promising strategy for reshaping maladaptive drug-context associations.
Neural basis of cognitive-perceptual and negative affect: the linking role of ventral anterior insula connectivity.
Han L, Li X, Zhang Y … +4 more , Chen J, Zhang J, Qiu J, Chen M
Neurosci Lett · 2026 Mar · PMID 41655807 · Publisher ↗
BACKGROUND: Schizotypal personality (SP) is characterized by cognitive-perceptual disturbances, interpersonal difficulties, and disorganized behavior. We examined associations between SP traits and affect, and insula-cen...
BACKGROUND: Schizotypal personality (SP) is characterized by cognitive-perceptual disturbances, interpersonal difficulties, and disorganized behavior. We examined associations between SP traits and affect, and insula-centered neural mechanisms underlying this link. METHODS: One hundred sixty-one university students completed the Schizotypal Personality Questionnaire-Brief and the Positive and Negative Affect Schedule and underwent resting-state fMRI. Seed-based whole-brain functional connectivity (FC) analyses used bilateral ventral anterior, dorsal anterior, and posterior insula seeds. Pearson correlations and mediation analyses tested associations among SP traits, negative affect, and FC. RESULTS: Cognitive-perceptual traits correlated positively with negative affect (r = 0.36, p < 0.001). FC between the right inferior parietal lobule (IPL.R) and the left ventral anterior insula (vAI.L) was positively correlated with cognitive-perceptual traits (r = 0.33, p < 0.001), whereas FC between the right cerebellar Crus I and the vAI.L was negatively correlated (r = -0.37, p < 0.001). FC between the right ventral anterior insula (vAI.R) and the Left Calcarine Gyrus (CAL.L) was also negative (r = -0.30, p < 0.001). vAI.L-IPL.R FC partially mediated the cognitive-perceptual traits-negative affect association (indirect effect = 0.1883, 95% bootstrap CI [0.0246, 0.4022]). CONCLUSION: vAI.L-IPL.R FC partially accounts for the link between cognitive-perceptual traits and negative affect, highlighting a potential neural pathway underlying affective vulnerability in SP.
Chronic alcohol consumption and abstinence disrupt cholinergic gene expression in the mesopontine tegmentum of alcohol-preferring iP rats.
Vaidya SP, Spark DL, Walker LC … +3 more , Pinares-Garcia P, Anversa RG, Lawrence AJ
Neurosci Lett · 2026 Mar · PMID 41655806 · Publisher ↗
The mesopontine tegmentum (MPT), consisting of the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDTg) regulates reward and aversion via direct projections to key regions including the striatum, substanti...
The mesopontine tegmentum (MPT), consisting of the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDTg) regulates reward and aversion via direct projections to key regions including the striatum, substantia nigra, and ventral tegmental area. Chronic alcohol consumption followed by abstinence significantly downregulates the M muscarinic receptor in the dorsolateral striatum. Since cholinergic projections from the mesopontine tegmentum (MPT) provide an external source of acetylcholine to this region, it is imperative to investigate how alcohol exposure and subsequent abstinence induce molecular alterations within the cholinergic system of the mesopontine tegmentum. In this study, we first characterised PPTg and LDTg projections to the dorsal striatum in alcohol-preferring iP rats, then assessed changes to cholinergic gene expression in the MPT following long-term voluntary alcohol consumption and abstinence. Using a combined retrograde tracing and immunofluorescence approach, we demonstrate that PPTg and LDTg provide direct, bilateral cholinergic innervation to both the dorsolateral and dorsomedial striatum, with less topographical specificity than previously reported in other strains. Following six months of intermittent alcohol access, RT-qPCR revealed a transient decrease in Chrna7 expression in the LDTg that returned to baseline after 14 days abstinence, and a downregulation of Chrm4 expression in the PPTg during abstinence. Together, these findings reveal that long-term voluntary alcohol consumption reconfigures mesopontine cholinergic signalling, which may contribute to the neurobiological underpinnings of AUD. SIGNIFICANCE STATEMENT: Long-term voluntary alcohol consumption reconfigures mesopontine cholinergic signalling, which may contribute to the neurobiological underpinnings of AUD.
Color modulation of motion aftereffect on optomotor response in zebrafish larvae.
Ulhaq ZS
Neurosci Lett · 2026 Mar · PMID 41654210 · Publisher ↗
Visual aftereffects are perceptual distortions that occur after prolonged exposure to a visual stimulus. We examined zebrafish larval behaviors in response to unidirectional or bidirectional grating movement in red, gree...
Visual aftereffects are perceptual distortions that occur after prolonged exposure to a visual stimulus. We examined zebrafish larval behaviors in response to unidirectional or bidirectional grating movement in red, green, and blue during adaptation and test phases. At the end of the test, larvae were collected to assess cone photoreceptor expression Unidirectional motion adaptation induced robust, color-dependent MAEs, with the strongest effect under red stimuli, followed by green and blue. In contrast, bidirectional adaptation abolished MAEs across all colors. General locomotor activity decreased during test phases, with unidirectional adaptation maintaining higher activity than bidirectional, particularly under red stimuli. Importantly, qRT-PCR and immunostaining revealed no changes in cone photoreceptor markers, indicating that the observed behavioral modulation occurred independently of photoreceptor expression. Together, these findings demonstrate that color selectively modulates motion perception in zebrafish larvae, with red stimuli producing the strongest motion adaptation effects, while general locomotor activity and photoreceptor expression remain largely unaffected. These behavioral patterns may arise from higher-order neural processing rather than from changes at the level of photoreceptor composition.
Sphingosine-1-phosphate attenuates seizures and cognitive deficits, associated with reduced hippocampal IL-1β in a PTZ-induced epilepsy model.
Luo K, Zeng W, Chen Q … +3 more , Ma Z, Huang S, Ben X
Neurosci Lett · 2026 Mar · PMID 41621476 · Publisher ↗
BACKGROUND AND AIM: Epilepsy is a prevalent neurological disorder frequently accompanied by cognitive impairments and neuronal damage. Neuroinflammation-particularly mediated by interleukin-1β (IL-1β)-plays a critical ro...
BACKGROUND AND AIM: Epilepsy is a prevalent neurological disorder frequently accompanied by cognitive impairments and neuronal damage. Neuroinflammation-particularly mediated by interleukin-1β (IL-1β)-plays a critical role in epileptogenesis. Sphingosine-1-phosphate (S1P), a bioactive lipid mediator, has been implicated in neuroprotection and anti-inflammatory signaling; however, its role in epilepsy remains unclear. This study aimed to investigate the effects and underlying mechanisms of S1P in a pentylenetetrazol (PTZ)-induced mouse model of epilepsy. METHODS: Male C57BL/6 mice were administered PTZ (33 mg/kg, i.p.) every other day for a total of 15 injections to establish a seizure-kindling model. S1P (0.5 mg/mL) was administered intraperitoneally during the subsequent treatment period. Seizure activity was assessed using electroencephalographic (EEG) recordings. Cognitive function was evaluated with the Morris water maze. Hippocampal neuronal morphology was examined via Nissl staining. The expression levels of IL-1β mRNA and precursor protein in the hippocampus were measured by qRT-PCR and Western blotting, respectively. RESULTS: S1P treatment significantly reduced seizure frequency and amplitude, shortened seizure duration, and ameliorated EEG abnormalities in epileptic mice. In behavioral assays, S1P improved spatial learning and memory performance. Histological analysis demonstrated reduced neuronal degeneration and preservation of hippocampal architecture in S1P-treated epileptic mice. Furthermore, S1P markedly decreased hippocampal IL-1β expression at both the mRNA and protein levels. CONCLUSIONS: S1P exerts anti-seizure and neuroprotective effects in PTZ-induced epileptic mice and attenuates IL-1β-mediated neuroinflammation. These findings suggest that the S1P-IL-1β axis may represent a promising therapeutic target for epilepsy and its associated cognitive impairments.
Autophagy activation by taurine alleviates prion-induced mitochondrial dysfunction and neurotoxicity.
Lee SO, Lee YJ
Neurosci Lett · 2026 Mar · PMID 41620010 · Publisher ↗
Taurine (2-aminoethanesulfonic acid) is a naturally abundant amino acid known to support mitochondrial stability and neuronal stress resistance; however, its role in prion peptide-induced neurotoxicity has not been estab...
Taurine (2-aminoethanesulfonic acid) is a naturally abundant amino acid known to support mitochondrial stability and neuronal stress resistance; however, its role in prion peptide-induced neurotoxicity has not been established. Here, we investigated whether taurine protects neuronal cells from toxicity induced by the prion protein fragment PrP(106-126) and whether autophagic flux contributes to this effect. Using an in vitro neuroblastoma cell model, we found that taurine pretreatment restored autophagic flux, as reflected by increased LC3-II/LC3-I ratios and reduced p62 accumulation. Taurine also attenuated PrP(106-126)-induced loss of mitochondrial membrane potential and apoptotic cell death. Importantly, inhibition of autophagic degradation with chloroquine prevented these protective effects, supporting a causal role for autophagy. These findings suggest that taurine mitigates prion peptide-mediated mitochondrial dysfunction by restoring autophagic flux in neuronal cells. While limited to a single in vitro model, this study provides foundational evidence that taurine-mediated modulation of autophagy may represent a potential therapeutic avenue for protein misfolding-related neurodegenerative disorders.
Altered brain glucose metabolism in nicotine use but not in hazardous alcohol consumption or problem gambling of healthy men.
Shin S, Kim K, Kim J … +3 more , Nam HY, Seok JW, Pak K
Neurosci Lett · 2026 Mar · PMID 41617147 · Publisher ↗
We aimed to determine whether chronic nicotine use, alcohol consumption, and gambling alters brain glucose metabolism. We retrospectively analyzed data from 131 healthy men who participated in health check-ups at Samsung...
We aimed to determine whether chronic nicotine use, alcohol consumption, and gambling alters brain glucose metabolism. We retrospectively analyzed data from 131 healthy men who participated in health check-ups at Samsung Changwon Hospital Health Promotion Center during 2013 (baseline) and 2018 (follow-up). The health checks included a brain F-fluorodeoxyglucose positron emission tomography (PET), a questionnaire of tobacco use, the Alcohol Use Disorders Identification Test (AUDIT; Korean version), and the Problem Gambling Severity Index (PGSI). From brain PET scans, the mean uptake in regions-of-interest was scaled to the mean global cortical uptake by each individual, defining the standardized uptake value ratio. We established a model for tobacco use, AUDIT, and PGSI with regional SUVR as a dependent variable and tobacco use, AUDIT, and PGSI as predictors adjusted for age using Bayesian hierarchical modelling. All data were analyzed using R (The R Foundation for Statistical Computing). This study included 131 healthy males (mean age at baseline and follow-up: 43.0 ± 3.4, 48.1 ± 3.3 years, respectively). Tobacco use was negatively associated with glucose metabolism in the caudate, thalamus, cingulate, and frontal lobe, and positively associated with the cerebellum, whereas AUDIT or PGSI were not associated with regional glucose metabolism. In conclusion, tobacco use was associated with altered brain glucose metabolism in the caudate, thalamus, cingulate, frontal lobe, and the cerebellum. However, neither hazardous alcohol consumption, nor problem gambling showed any association with brain glucose metabolism. Our findings might provide new insights into the neural mechanisms of chronic nicotine use.
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