Behavioral And Brain Functions[JOURNAL]
Sun
200 papers
Quercetin nanoemulsion ameliorates tremor and neuroinflammatory dysregulation: behavioral and molecular insights in a mouse model of essential tremor.
Pirmoradi Z, Soti M, Kohlmeier KA … +2 more , Shabani M, Shahsavari F
Behav Brain Funct · 2025 Dec · PMID 41354816 · Full text
BACKGROUND: Essential tremor (ET) is a common movement disorder characterized by persistent limb tremors. Currently, no effective treatment for ET exists. Natural plant-derived compounds, like the flavonoid, quercetin ma...
BACKGROUND: Essential tremor (ET) is a common movement disorder characterized by persistent limb tremors. Currently, no effective treatment for ET exists. Natural plant-derived compounds, like the flavonoid, quercetin may provide therapeutic benefits, particularly when delivered in nanoemulsion formulations that enhance bioavailability and efficacy. This study evaluated the neuroprotective potential of quercetin nanoemulsion (Que-NE) in a harmaline-induced mouse model of ET. METHODS: Thirty-two male Swiss mice were randomly divided into four groups (n = 8 each): Control, Harmaline (10 mg/kg, i.p., on days 3, 5, and 7), Que-NE (20 mg/kg, i.p., for 7 days), and Harmaline + Que-NE. Harmaline was used to reliably induce tremor via olivocerebellar hyperexcitability. Behavioral performance was assessed using the open field, elevated plus maze, tail suspension, wire grip, rotarod, and passive avoidance tests. Expression of NF-κB, TNF-α, IL-1β, IL-6, NMDA receptor, and Lingo-1 was determined by RT-PCR. RESULTS: Que-NE significantly reduced harmaline-induced tremor severity (p < 0.0001), decreased immobility time in the tail suspension test (p = 0.0003), and improved open field anxiety-like behaviors compared with harmaline alone (P = 0.0012). Que-NE downregulated pro-inflammatory mediators (P < 0.0001) and reduced Lingo-1 gene expression (P < 0.0001). However, Que-NE showed limited efficacy in severe motor coordination tasks (rotarod, wire grip) and passive avoidance memory. CONCLUSIONS: Que-NE exerts measurable anti-inflammatory, anxiolytic, and antidepressant-like effects in the harmaline model of ET. The impact of Que-NE on improving motor deficits, reducing inflammatory markers, and suppressing inhibitors of synaptic plasticity highlights the potential of Que-NE as a disease-modifying strategy. However, dose-response, protein-level, and long-term studies are needed to evaluate the therapeutic potential of Que-NE for ET management.
Overexpression of Hspa1b in the mouse hippocampus may be associated with major depressive disorder.
Zhao X, Shang Y, Zhu W … +5 more , Wareesawetsuwan N, Zhu L, Li C, Chen J, Bi Y
Behav Brain Funct · 2025 Nov · PMID 41299718 · Full text
Heat Shock Protein Family A Member 1B (Hspa1b) is an RNA binding protein that regulates transcriptional and post transcriptional processes. Previous studies have suggested its protective role in stress adaptation and pos...
Heat Shock Protein Family A Member 1B (Hspa1b) is an RNA binding protein that regulates transcriptional and post transcriptional processes. Previous studies have suggested its protective role in stress adaptation and post injury depression, as well as its potential therapeutic effects following antidepressant treatment in major depressive disorder (MDD). However, its direct involvement in MDD remains unclear. In this study, a mouse model with hippocampal Hspa1b overexpression was established. Integrated RNA immunoprecipitation sequencing (RIP seq) and RNA sequencing (RNA seq) were performed to investigate Hspa1b mediated transcriptional regulation and alternative splicing. Overexpression of Hspa1b resulted in 401 differentially expressed genes (DEGs), including downregulation of several neuroinflammatory genes such as Lcn2, Ccl5, and Cd52, upregulation of oxytocin/neurophysin I prepropeptide (Oxt), and downregulation of intercellular adhesion molecule 1 (Icam1), which are all associated with depression pathogenesis. In addition, 1,397 significantly altered Hspa1b regulated alternative splicing events were identified. RT qPCR confirmed splicing changes in six genes, including Spata13 and Ptpro, among others linked to depression and neuronal functions. These findings demonstrate that hippocampal Hspa1b overexpression is associated with transcriptional and splicing alterations in genes related to immune, neuronal, and HPA axis pathways, which are key mechanisms implicated in MDD. Based on these alterations, Hspa1b may act as a double-edged regulator in MDD, warranting further investigation of its causal role and therapeutic potential.
Sex-dimorphic oxytocin regulation of CA1-dependent spatial memory and synaptic plasticity in juvenile rats.
Shehadeh E, Rajan Narattil N, Kritman M … +1 more , Maroun M
Behav Brain Funct · 2025 Nov · PMID 41291824 · Full text
Research into memory mechanisms has predominantly centered on adult male rodents, often overlooking the influences of sex and developmental stage. Memory processes vary significantly between juveniles and adults, with se...
Research into memory mechanisms has predominantly centered on adult male rodents, often overlooking the influences of sex and developmental stage. Memory processes vary significantly between juveniles and adults, with sex acting as a critical determinant. Oxytocin (OXT) has emerged as a key modulator of fear responses and extinction in a sex-dependent manner, with prepubertal females displaying OXT-dependent contextual extinction patterns akin to adult males. These differences likely stem from diverse trajectories of hippocampal and prefrontal cortex maturation. This study examines the CA1 region's involvement in object location memory (OLM), social recognition memory (SRM), and synaptic plasticity among juvenile male and female rats, focusing on OXT's role. Results reveal that, in juvenile (postnatal day -PND 27) protein synthesis inhibition or OXT receptor blockade with OXT receptor antagonist (OXTR-Ant) in CA1 impairs OLM and impairs long-term potentiation (LTP) uniquely in males. These findings correlate with a greater increase in CA1 c-Fos expression following OLM in juvenile males compared to females. The SRM impairment was uniform across sexes under these treatments. In adults (PND 69), OXTR-Ant caused OLM impairment solely in females. These findings underscore pronounced sex- and age-specific variations in CA1-dependent memory and synaptic plasticity, shedding light on distinct neurobiological mechanisms that emerge pre-puberty and evolve throughout development.
Aging-related changes in cognitive flexibility: fMRI meta-analysis.
Chuikova Z, Faber A, Filatov A … +3 more , Myachykov A, Shtyrov Y, Arsalidou M
Behav Brain Funct · 2025 Nov · PMID 41243112 · Full text
Cognitive flexibility-the ability to adaptively shift between different mental processes-is essential for human functioning. This meta-analysis examines age-related changes in neural correlates of cognitive flexibility u...
Cognitive flexibility-the ability to adaptively shift between different mental processes-is essential for human functioning. This meta-analysis examines age-related changes in neural correlates of cognitive flexibility using two common assessments: the Wisconsin Card Sorting Test (rule-discovery) and Task-Switching Paradigm (rule-retrieval). We synthesized findings from 85 articles comprising 118 experiments with 2246 participants across young, middle-age, and older adult groups. Activation Likelihood Estimation analyses revealed an age-related decrease in neural involvement, particularly in posterior regions, with an anterior shift in older adults. Younger adults exhibited bilateral activation patterns while older adults showed left-dominant activity, indicating neural circuit redistribution. Rule-retrieval tasks consistently engaged left-lateralized frontoparietal regions across all age groups, with middle-age adults additionally recruiting the right cerebellum and medial frontal gyrus. For rule-discovery tasks, age-related changes were observed in bilateral frontoparietal regions, with older adults showing unique activation in the left inferior frontal gyrus. These findings highlight differential aging trajectories for rule-retrieval versus rule-discovery processes, reflecting changes in neural mechanisms with aging. Furthermore, middle-age adults recruited additional regions related to conflict monitoring, whereas older adults relied more on planning-related areas, suggesting strategy differences. Our study provides critical insights into the neural underpinnings of cognitive flexibility and its age-related changes, emphasizing the need for research on mechanisms and task-specific age trajectories.
Downregulation of p120 catenin in the mouse hippocampus contributes to the development of depression-like phenotypes.
Chen C, Feng LP, Shi PL … +6 more , Liu Q, Zhang LW, Wang Q, Hua RF, Su X, Li WQ
Behav Brain Funct · 2025 Nov · PMID 41239505 · Full text
BACKGROUND: Major depressive disorder (MDD) is a highly prevalent psychiatric disorder and one of the leading causes of disability worldwide. Neuroinflammation is strongly implicated in the pathophysiology of MDD, sugges...
BACKGROUND: Major depressive disorder (MDD) is a highly prevalent psychiatric disorder and one of the leading causes of disability worldwide. Neuroinflammation is strongly implicated in the pathophysiology of MDD, suggesting that regulators of neuroinflammatory signaling are feasible therapeutic targets. The CTNND1 gene encodes a member of the armadillo protein family termed p120 (or catenin delta) that functions in cell-cell adhesion and signal transduction, including among immune cells, suggesting immunomodulatory activity. RESULTS: We report that systemic injection of the bacterial toxin lipopolysaccharide (LPS) induced depression-like behaviors in mice while concomitantly activating the neuroinflammatory NF-κB signaling pathway, upregulating interleukin (IL)-1β expression, and reducing p120 expression in the hippocampus. Moreover, shRNA-mediated knockdown of hippocampal p120 expression also activated the NF-κB signaling pathway, enhanced IL-1β expression, and induced the same depression-like behaviors. Similarly, both LPS treatment and p120 knockdown upregulated pNF-κB and IL-1β levels in pheochromocytoma-12 cells. CONCLUSIONS: These findings suggest that p120 may function to prevent the development or expression of depressive symptoms by suppressing proinflammatory NF-κB-IL-1β signaling in the hippocampus. Targeting p120 may be a feasible therapeutic strategy to treat MDD.
PBM alleviates depression and anxiety like behaviors in mice: insight from local field potential.
Tan Y, Liu J, Qiu Y … +6 more , Ruan H, Qin Q, Li X, Xu Z, Qiao X, Jiang X
Behav Brain Funct · 2025 Nov · PMID 41239492 · Full text
BACKGROUND: Depression involves abnormal neural oscillations. Photobiomodulation (PBM) modulates such oscillations but lacks behavioral electrophysiological mechanistic studies. We explored PBM's effects on hippocampal C...
BACKGROUND: Depression involves abnormal neural oscillations. Photobiomodulation (PBM) modulates such oscillations but lacks behavioral electrophysiological mechanistic studies. We explored PBM's effects on hippocampal CA1 oscillations and phase-amplitude coupling (PAC) in a depression model. METHODS: Male C57BL/6J mice were randomly divided into saline, LPS (2 mg/kg i.p.), and LPS + PBM groups (n = 10/group for behavioral tests, n = 8/group for electrophysiology). LPS groups received lipopolysaccharide to induce neuroinflammation. The LPS + PBM group underwent 810 nm PBM (20 mW/cm², 12 min/day × 4 days) starting day 4 post-injection. Anxiety- and depression-like behaviors were assessed via open field, elevated plus-maze, and tail suspension tests. Wireless electrophysiology recorded CA1 local field potentials (LFP) during rest and behaviors. Oscillations and PAC were analyzed. Data are presented as mean ± SD; group differences were evaluated by one-way ANOVA with Bonferroni post-hoc correction and ɳ² effect sizes, with two-tailed p < 0.05 taken as statistically significant. RESULTS: PBM (20 mW/cm) alleviated LPS-induced anxiety and depressive behaviors. Electrophysiologically, PBM restored resting-state δ power (LPS + PBM: 0.0499 ± 0.0282, LPS: 0.1491 ± 0.0887; p < 0.01) and enhanced δ-γ coupling (LPS + PBM: 2.049 ± 0.447, LPS: 0.230 ± 0.298; p < 0.05). During anxiety tasks, PBM suppressed γ power (LPS + PBM: 0.3709 ± 0.1569, LPS: 0.5165 ± 0.06896; p < 0.05) and strengthened δ-γ PAC (LPS + PBM: 0.741 ± 0.508 vs. LPS: 0.217 ± 0.218, p < 0.05). In depression tests, PBM normalized δ power (LPS + PBM: 0.0261 ± 0.0182, LPS: 0.1315 ± 0.0619; p < 0.001) and reduced γ power (LPS + PBM: 0.2848 ± 0.0921, LPS: 0.4067 ± 0.0892; p < 0.05). No significant PAC changes was observed during depression tasks. CONCLUSION: PBM therapy ameliorates LPS-induced depression and anxiety behaviors while normalizing hippocampal CA1 oscillations and cross-frequency coupling. Its effects are state-dependent, modulating distinct frequency bands and PAC across rest and behavioral contexts, revealing potential electrophysiological therapeutic mechanisms.
The effect of intracerebroventricular injection of insulin-like growth factor-1 on morphine-induced conditioned place preference extinction and reinstatement; a behavioral and biochemical experimental study.
Ghadirzadeh E, Gheibi M, Siahposht-Khachaki A … +4 more , Vahdati Helan E, Farvardin M, Shadi S, Abdolkarimi A
Behav Brain Funct · 2025 Nov · PMID 41225597 · Full text
BACKGROUND: Morphine addiction is a growing problem with severe consequences. Interestingly, Insulin-like Growth Factor-1 (IGF-1), a hormone with the ability to modulate neural pathways and exert neuroprotective and rege...
BACKGROUND: Morphine addiction is a growing problem with severe consequences. Interestingly, Insulin-like Growth Factor-1 (IGF-1), a hormone with the ability to modulate neural pathways and exert neuroprotective and regenerative properties, could emerge as a potential treatment. However, to the best of our knowledge, the role of IGF-1 in the extinction and reinstatement phases of morphine induced conditioned place preference (CPP) remains unexplored. Thus, this study aimed to investigate the behavioral and biochemical effects of intracerebroventricular (ICV) IGF-1 administration on extinction and reinstatement after morphine induced CPP and c-Fos expression in nucleus accumbens (NAc). METHODS: Rats were conditioned with morphine (5 mg/kg, subcutaneously). The study examined alterations in CPP scores after administering varying multiple doses of IGF-1 (5, 10, and 20 µg) daily during the extinction and reinstatement phases of CPP, or single 20 µg dose administration prior to the extinction or prior to the reinstatement phase. Following these procedures, c-Fos levels in the NAc were quantified using the ELISA method. RESULTS: The findings revealed that daily administration of IGF-1 at doses of 5, 10, and 20 µg resulted in a dose-dependent reduction in conditioning scores and shorter extinction period. Importantly, only the 20 µg attenuated morphine reinstatement significantly. Additionally, c-Fos levels, which increased following morphine exposure, were markedly reduced by IGF-1 administration across all phases. CONCLUSION: This study demonstrates that IGF-1 administration could facilitates the extinction and attenuate the reinstatement of morphine-induced CPP, highlighting its potential as a therapeutic strategy in opioid addiction.
Cannabinoid type 1 receptors in the mice prefrontal cortex regulate object location memory acquisition via GABAergic neurons.
Tokutake T, Yokose J, Yano Y … +3 more , Shigetsura Y, Muramatsu SI, Nitta A
Behav Brain Funct · 2025 Nov · PMID 41188973 · Full text
BACKGROUND: Adverse psychiatric symptoms caused by cannabis are a significant concern, and Δ9-tetrahydrocannabinol (THC) has been identified as a key contributor to these symptoms. THC binds to cannabinoid type 1 recepto...
BACKGROUND: Adverse psychiatric symptoms caused by cannabis are a significant concern, and Δ9-tetrahydrocannabinol (THC) has been identified as a key contributor to these symptoms. THC binds to cannabinoid type 1 receptors (CB1Rs), which are abundant in the brain and associated with cognition. The prefrontal cortex (PFC) is crucial for cognitive functions. However, the functions of CB1Rs in the PFC in cognition processes remain unclear. Here, we injected arachidonylcyclopropylamide (ACPA), a CB1Rs agonist, into the PFC of male C57BL/6J mice via the cannula and conducted cognitive tests, including the novel object recognition test and object location test (OLT). RESULTS: These tests assessed memory in three stages: acquisition, consolidation, and retrieval. ACPA was administered immediately before each stage, and its intra-PFC administration specifically impaired memory acquisition in the OLT. In addition, in vivo microdialysis revealed that ACPA reduced extracellular GABA levels within the PFC. Next, we produced an adeno-associated virus with a glutamic acid decarboxylase promoter and an hM3Dq-encording chemogenic activator to activate GABAergic neurons in the PFC. Subsequently, deschloroclozapine (DCZ), an hM3Dq agonist, restored the memory acquisition impaired by ACPA. CONCLUSION: Our findings suggest that CB1Rs in the PFC are involved in memory acquisition through the regulation of GABA release, offering new insights into how cannabis use lead to cognitive impairment.
Differential cognitive enhancer effects of acetylcholinesterase inhibitors and memantine on age-related deficits in vigilance and sustained attention: a preclinical validation study.
Bali ZK, Bruszt N, Göntér K … +1 more , Hernádi I
Behav Brain Funct · 2025 Oct · PMID 41152946 · Full text
BACKGROUND: The psychomotor vigilance task (PVT) is a cognitive test commonly used to measure sustained attention and vigilance in humans in healthy and diseased states. Here, we aimed to utilize a recently designed rat...
BACKGROUND: The psychomotor vigilance task (PVT) is a cognitive test commonly used to measure sustained attention and vigilance in humans in healthy and diseased states. Here, we aimed to utilize a recently designed rat version of the PVT to assess potential cognitive enhancer effects of various pharmacological compounds in a natural model of age-related cognitive decline. Therefore, we treated aged rats (> 28 months old) with different doses of three approved Alzheimer's disease drugs: donepezil, galantamine, and memantine. RESULTS: Aged rats made significantly slower responses to the cue stimuli compared to young animals and fewer correct responses, mainly because of an increased number of missed trials (i.e., when the trial was not initiated by the rat). Donepezil improved the performance of aged rats by accelerating their responses at a dose of 0.03 mg/kg. However, galantamine treatment showed no beneficial effects on either reaction time or the number of correct trials. Furthermore, both donepezil (0.3 and 1.0 mg/kg) and galantamine (3.0 mg/kg) increased the reaction time and number of missed trials at high doses. Memantine did not affect the reaction time of aged rats, but it increased the number of correct responses at 0.1 and 0.3 mg/kg doses. CONCLUSIONS: Here, we showed that PVT is suitable for addressing pharmacological effects on various cognitive domains in a single behavioral paradigm. Our findings also indicate that different cognitive enhancer compounds (even when their targets are thought to be the same) may differentially influence distinct cognitive domains and modulate task performance.
Motor expertise shapes crossmodal and modality-specific action representations in table tennis players.
Mou H, Liu L, Wang Y
Behav Brain Funct · 2025 Oct · PMID 41034983 · Full text
Multivariate neuroimaging studies have shown a functional dissociation between the temporal and frontoparietal cortices in action representation. However, it remains unclear to what extent this specificity is modulated b...
Multivariate neuroimaging studies have shown a functional dissociation between the temporal and frontoparietal cortices in action representation. However, it remains unclear to what extent this specificity is modulated by motor experience. To address this question, we employed functional magnetic resonance imaging-based multivoxel pattern analysis (MVPA). Neural activation patterns were compared between professional table tennis players (experts) and novices during the passive observation of action videos and the reading of corresponding action-related sentences. Specifically, to identify brain regions that decode perceptual-motor information, classifiers were trained and tested within the same stimulus modality (video or sentence). To identify brain regions supporting conceptual-level action decoding, classifiers trained on video stimuli were tested on sentence stimuli, and vice versa. The results revealed that, in experts, the left lateral posterior temporal cortex (LPTC) and anterior temporal lobe (ATL) supported crossmodal action representations, whereas the left superior parietal lobule (SPL) and precentral gyrus (PreCG) exhibited modality-specific representations, particularly in response to video-based stimuli. In novices, only the PreCG showed modality-specific representations for video stimuli. These findings suggest a functional dissociation across brain regions, with the temporal cortex involved in conceptual-level representations of actions andthe SPL associated with processing perceptual-motor features. While such representations were more prominent in experts for familiar actions, the PreCG showed modality-specific representations regardless of group. These results highlight potential group-level differences in the neural encoding of action-related information, which may reflect the influence of task familiarity or prior sensorimotor experience.
Disruption of circadian rhythms and behavior in Drosophila melanogaster induced by Epstein-Barr virus: insights into viral infections and host physiology.
Naim G, Znait S, Sherri N … +2 more , Rahal EA, Shirinian M
Behav Brain Funct · 2025 Sep · PMID 41029708 · Full text
Epstein-Barr virus (EBV) has been extensively studied for its associations with autoimmune disorders, various cancers, and neurological diseases. Emerging evidence also links EBV to behavioral and neurophysiological disr...
Epstein-Barr virus (EBV) has been extensively studied for its associations with autoimmune disorders, various cancers, and neurological diseases. Emerging evidence also links EBV to behavioral and neurophysiological disruptions, potentially mediated through interactions with host's immune and circadian systems. In this study, we investigated the effects of EBV and its DNA on the behavior of Drosophila melanogaster by examining its lifespan, activity, sleep, and circadian rhythms. Both EBV viral particles and EBV DNA showed distinct effects in terms of behavior and survival. Circadian function analysis showed disruptions in several circadian parameters in EBV-injected flies, whereas EBV DNA-injected flies displayed defects in sleep behavior. Our findings suggest that EBV may impact circadian mechanisms, thereby enhancing our understanding of the effects of viral infections on circadian and behavioral systems and establishing Drosophila as a valuable model for future studies on EBV and host physiology.
Copper loading may affect rat neurobehaviour by impairing mitochondria-associated endoplasmic reticulum membranes in hippocampal neurons.
Sun Z, Jin S, Fang X … +2 more , Yang W, Chen H
Behav Brain Funct · 2025 Sep · PMID 41029335 · Full text
BACKGROUND: To observe the effects of copper sulfate (CuSO)-induced copper loading on neurobehaviour, mitochondria-associated endoplasmic reticulum membranes (MAMs) and related regulatory proteins in the hippocampal CA1...
BACKGROUND: To observe the effects of copper sulfate (CuSO)-induced copper loading on neurobehaviour, mitochondria-associated endoplasmic reticulum membranes (MAMs) and related regulatory proteins in the hippocampal CA1 region of Sprague-Dawley (SD) rats. METHODS: Forty SD male rats were randomly divided into control and copper loading groups of 20 rats each. The control group rats were fed with normal feed and water; rats in the copper loading group were fed high copper feed (containing 1g/kg of CuSO) and CuSO deionized water (concentration of 0.185%). After 12 weeks of rearing, the morris water maze (MWM) task and novel object recognition (NOR) test were conducted to compare the neurobehavioral characteristics of the two groups of rats. Morphological changes of neuronal MAMs in the hippocampal CA1 region of copper-loaded rats were observed using a transmission electron microscope (TEM) and immunofluorescence double-labelling techniques. Western-blot analysis was used to detect the expression of MAMs proteins VDAC1, IP3R, GRP75 and Mfn2. RESULTS: The results revealed that rats in the copper-loading group had significantly prolonged escape latency and reduced number of platform crossings in the MWM task (p < 0.01). The percentage of novel objects explored (also known as the Discrimination Ratio, DR) and the discrimination index (DI) were significantly reduced in the NOR test (p < 0.01). In addition, electron microscopy shows increased disruption of neuronal endoplasmic reticulum (ER)-mitochondrion coupling in the hippocampal CA1 region of rats in the copper-loading group (p < 0.05), and the percentage of MAMs in mitochondrial circumference decreased (p < 0.05), the colocalization coefficients between the ER and mitochondria was significantly reduced (p < 0.05). Moreover, the protein expression levels of VDAC1, IP3R, and GRP75 in rat hippocampal tissue were detected to be significantly increased (p < 0.01), while the protein expression level of Mfn2 was significantly decreased (p < 0.01). CONCLUSIONS: In this study, it is speculated that the neurobehavioral changes in rats may be related to the increased expression levels of the MAMs proteins VDAC1, IP3R, and GRP75, the reduced expression level of Mfn2, and the disruption of the structural integrity of MAMs in the hippocampal CA1 region of rats caused by copper loading.
Representation of top-down versus bottom-up attention in the right dorsolateral prefrontal cortex and superior parietal lobule.
Zhang Q, Li W, Zhang T … +4 more , Xiong R, Zhang J, Jin Z, Li L
Behav Brain Funct · 2025 Sep · PMID 41024222 · Full text
BACKGROUND: Visual selective attention can be categorized into top-down (goal-driven) and bottom-up (stimulus-driven) attention, with the fronto-parietal network serving as the primary neural substrate. However, fewer st...
BACKGROUND: Visual selective attention can be categorized into top-down (goal-driven) and bottom-up (stimulus-driven) attention, with the fronto-parietal network serving as the primary neural substrate. However, fewer studies have focused on the specific roles of the right dorsolateral prefrontal cortex (DLPFC) and superior parietal lobule (SPL) in top-down and bottom-up attention. This study aimed to investigate the activity and connectivity of the right DLPFC and SPL in top-down and bottom-up attention. METHODS: Visual pop-out task mainly induces bottom-up attention, while the visual search task mainly induces top-down attention. Fifty-four participants completed the pop-out and search tasks during functional magnetic resonance imaging (fMRI) scanning. We used univariate analyses, multivariate pattern analyses (MVPA), and generalized psychophysiological interaction (gPPI) to assess activity and functional connectivity. RESULTS: Univariate analyses revealed stronger activation in the right DLPFC and SPL during the search > pop-out condition. The activation of the DLPFC was driven by its deactivation in the pop-out task, whereas the SPL showed significant activation in both tasks. MVPA demonstrated that activation patterns in the right DLPFC and SPL could distinguish between the pop-out and search tasks above chance level (0.5), with the right SPL exhibiting higher classification accuracy. The gPPI analyses showed that higher functional connectivity between the two seeds (right DLPFC and SPL) and bilateral precentral gyrus, left SPL, and right insula. CONCLUSIONS: These results indicate that the right DLPFC and SPL showed stronger activity and connectivity under top-down versus bottom-up attention, allowing for neural representation of visual selective attention. This study provides evidence for understanding the role of the fronto-parietal network in visual selective attention.
Isoacteoside alleviates LPS-induced depressive-like behaviors in mice by inhibiting neuroinflammation through regulating microglial polarization and oxidative stress.
Bi J, Zhang H, Wei J … +8 more , Huang X, Dong Y, Dong Y, Xie Y, Li R, Chen S, Zhao Z, Cheng B
Behav Brain Funct · 2025 Sep · PMID 41024195 · Full text
Recent studies have demonstrated a close association between neuroinflammation and depression. Isoacteoside (ISO) has recently been reported to exhibit anti-inflammatory properties. However, the effects of ISO on neuroin...
Recent studies have demonstrated a close association between neuroinflammation and depression. Isoacteoside (ISO) has recently been reported to exhibit anti-inflammatory properties. However, the effects of ISO on neuroinflammation-induced depression and its underlying mechanisms have not been fully elucidated. This study aimed to investigate the mechanism of ISO on neuroinflammation-induced depression from both in vivo and in vitro aspects. In the in vivo experiments, lipopolysaccharide (LPS) was used to induce depressive-like behavior in adult male C57BL/6J mice, which were subsequently detected using the open field test (OFT), forced swim test (FST), and tail suspension test (TST). Quantitative real-time polymerase chain reaction (qPCR) and western blot were employed to measure the expression of inflammatory and polarization markers, as well as related proteins. Immunofluorescence staining was used to detect the expression of glial cell markers. For the in vitro experiments, BV2 and SH-SY5Y cells were selected and treated with LPS for subsequent analysis. The results indicated that mice treated with LPS exhibited depressive-like behaviors, accompanied by significant levels of neuroinflammation and oxidative stress, all of which were effectively reduced by ISO treatment. Furthermore, ISO facilitated the normalization of microglial polarization from the M1 to M2 phenotype, reduced the expression of ionized calcium-binding adaptor 1 (Iba1) and glial fibrillary acidic protein (GFAP), and modulated the CREB/BDNF signaling pathway. These findings suggest that ISO has an ameliorative effect on LPS-induced depressive-like behavior in mice, which may be achieved by attenuating neuroinflammation and oxidative stress as well as modulating the phenotype of microglia.
PHLPP1 deficiency alleviates dopaminergic neurodegeneration and represses neuroinflammation in Parkinson's disease.
Chen Z, Liu Y, Zhao J … +5 more , Zhou X, Han Y, Zhou Z, Liang H, Bi Y
Behav Brain Funct · 2025 Sep · PMID 41024062 · Full text
BACKGROUND: Pleckstrin homology (PH) domain leucine-rich repeat protein phosphatases (PHLPP) has been associated with several neurodegenerative diseases, however, few studies have investigated the role of PHLPP in Parkin...
BACKGROUND: Pleckstrin homology (PH) domain leucine-rich repeat protein phosphatases (PHLPP) has been associated with several neurodegenerative diseases, however, few studies have investigated the role of PHLPP in Parkinson's disease (PD). The present study aimed to answer this question through establishing a Parkinson's disease (PD) model using the Phlpp1-/- and wild-type (WT) mice and testing their behavioral as well as molecular changes. METHODS: MPTP was intraperitoneal injected into mice to generate a PD model. Neurobehavioral parameters, protein expression and inflammatory cytokines release were measured by the open filed test, the pole test, immunohistochemistry, immunoblotting, immunoprecipitation, and quantitative reverse transcription PCR. RESULTS: MPTP-induced neurobehavioral deficits were more significantly ameliorated in PHLPP-KO-MPTP mice compared to WT-MPTP mice. The survival rate of TH neurons in the PHLPP-KO-MPTP group was higher than that in the WT-MPTP group (66% vs. 38%). Additionally, PHLPP1 knockout in KO-MPTP mice markedly reduced levels of IL-1β, IL-6, TNF-α, and iNOS, and increased levels of TGF-β compared to those of WT-MPTP mice. Furthermore, PHLPP1 was found to bind to NLRP3 and that PHLPP1 knockout inhibited MPTP-induced expression of IL-1β and caspase-1 in substantia nigra of PD model mice. CONCLUSION: Our results demonstrates that PHLPP1 knockout in PD model is positively associated with the survival of TH + neurons by suppressing inflammatory response in substantia nigra, suggesting that PHLPP1 plays a critical role in the development of PD.
Correction: Spectral tuning and after‑effects in neural entrainment.
Menetrey MQ, Pascucci D
Behav Brain Funct · 2025 Sep · PMID 40973946 · Full text
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TREK-1 and epilepsy: regulating the balance of K and the glutamate release in astrocyte-neuron interactions.
Yang J, Li L, Xu Y … +2 more , Guan Y, Li X
Behav Brain Funct · 2025 Aug · PMID 40887605 · Full text
The TWIK-related K channel (TREK-1), a member of the two-pore domain potassium(K2P) family, is characterized as a "leaky potassium channel" and is integral to the maintenance of the resting membrane potential. As the mos...
The TWIK-related K channel (TREK-1), a member of the two-pore domain potassium(K2P) family, is characterized as a "leaky potassium channel" and is integral to the maintenance of the resting membrane potential. As the most abundant cell type in the central nervous system, astrocytes play important roles in the development of epilepsy by regulating the release of glutamate and the function of potassium channels. Previous studies have revealed that TREK-1 is involved in a range of neurological diseases, including epilepsy. In astrocytes, TREK-1 acts as a crucial regulator of the rapid release of glutamate and passive conductance. However, controversy remains about the expression levels of TREK-1-binding receptors in the process of the release and recycling of glutamate in tripartite synapses. Thus, elucidating the pathological mechanisms involving TREK-1 in epilepsy could significantly increase our understanding of the pathophysiological basis of diseases and facilitate the identification of potential targets for novel therapeutic interventions. Here, we review the physiological function of TREK-1 and studies examining the role of TREK-1 in epilepsy, with a particular emphasis on its interactions with glutamate at tripartite synapses. Furthermore, we provide an analysis of the associated molecular mechanisms of this channel and conclude with an outlook on impending studies on TREK-1 as a novel therapeutic target for epilepsy.
Behavioral variant frontotemporal dementia as a model for understanding the cognitive and cerebral determinants of verbal creativity.
Altmayer V, Ovando-Tellez M, Bieth T … +13 more , Batrancourt B, Rametti-Lacroux A, Bernardaud L, Moreno-Rodriguez S, Vigreux L, Ledu V, Garcin B, Migliaccio R, Le Ber I, Lopez-Persem A, Levy R, Volle E, ECOCAPTURE study group
Behav Brain Funct · 2025 Aug · PMID 40849488 · Full text
BACKGROUND: Although creativity is an essential cognitive function to adapt to an ever-changing world, its neurocognitive and cerebral bases still need clarification. Current models highlight the interaction between asso...
BACKGROUND: Although creativity is an essential cognitive function to adapt to an ever-changing world, its neurocognitive and cerebral bases still need clarification. Current models highlight the interaction between associative and executive processes underpinned by the default mode (DMN), executive control (ECN) and salience networks (SN). Furthermore, recent neuroimaging studies highlight the key role of the prefrontal cortex (PFC), located at the crossroads of these networks. Hence, behavioral variant frontotemporal dementia (bvFTD), characterized by progressive neurodegeneration principally impacting the prefrontal cortex and the intrinsic connectivity of these three creativity-related networks, represents a unique model to study creativity. In this study involving 14 bvFTD patients and 20 matched controls, we used a simple word-to-word association task (FGAT) to explore the specific cognitive processes involved in remote thinking, i.e., the production of creative semantic associations. Using voxel-based morphometry, we uncovered critical brain regions for each component and then characterized these regions' intrinsic connectivity profiles using resting-state functional connectivity in healthy controls. RESULTS: We dissociated four key cognitive components underlying remote thinking: spontaneous associative thinking, inhibition of unoriginal responses, intentional remote associative thinking, and verbal initiation; and replicated them in three independent datasets. Spontaneous associative thinking relied on temporal and cerebellar regions involved in low-order and automatic semantic processing, connected with the DMN, ECN and SN. Inhibition of prepotent unoriginal responses depended on key nodes of the SN. The ability to intentionally generate remote semantic associations was underpinned by key regions of the DMN. Finally, initiation of verbal responses relied on the right dorsolateral PFC, connected to the ECN. BvFTD patients were impaired in the last three components. Two components, cognitive inhibition and intentional remote thinking, mediated the link between atrophy in critical regions and an independent measure of creative abilities. CONCLUSIONS: These findings advance our understanding of creative neurocognition, distinguishing components of creative thinking and clarifying their critical cerebral bases, and participate in the characterization of creativity impairment in patients with bvFTD.
C18:0 GM3 ganglioside's efficacy in LPS-induced parkinsonism: neuroprotection, inflammatory inhibition and gliosis mitigation.
Liu TT, Liu CT, Li IH … +7 more , Chu YC, Hung HY, Chiu CH, Chou TK, Li SY, Wang TA, Shih JH
Behav Brain Funct · 2025 Jul · PMID 40713782 · Full text
BACKGROUND: Parkinson's disease (PD) is an incurable neurological disorder, and current pharmacological therapies primarily address symptoms without halting disease progression. Emerging evidence highlights PD as a neuro...
BACKGROUND: Parkinson's disease (PD) is an incurable neurological disorder, and current pharmacological therapies primarily address symptoms without halting disease progression. Emerging evidence highlights PD as a neuroinflammatory disease, with chronic brain inflammation preceding the onset of motor dysfunction. This study investigates the role of C18:0 GM3, a long-chain fatty acids-containing ganglioside, in modulating inflammatory responses in PD, exploring its therapeutic potential in mitigating LPS-induced parkinsonism. METHODS: Male C57BL/6 mice were utilized in an LPS-induced PD model to evaluate the neuroprotective effects of C18:0 GM3 ganglioside. Pre-treatment with C18:0 GM3 was assessed through behavioral tests, including rotarod and beam-walking, to determine motor function improvements. Dopaminergic neurotoxicity was quantified using [F]FE-PE2I positron emission tomography (PET) imaging and tyrosine hydroxylase (TH) staining. The anti-inflammatory and anti-gliosis effects of C18:0 GM3 were analyzed by measuring cytokine levels (IL-1β, TNF-α) and by assessing Iba1 and GFAP immunoreactivity as indicators of microglial and astrocytic changes, respectively. RESULTS: Pre-treatment with C18:0 GM3 ganglioside significantly enhanced motor coordination and balance, as evidenced by improved performance in rotarod and beam-walking tests. Furthermore, C18:0 GM3 ganglioside effectively attenuated LPS-induced dopaminergic neurotoxicity, evidenced by increased striatal dopamine transporter availability on [F]FE-PE2I PET imaging and the preservation of TH-positive neurons in the striatum. In addition, C18:0 GM3 markedly suppressed the expression of pro-inflammatory cytokines, including IL-1β and TNF-α, along with cyclooxygenase-2 levels. C18:0 GM3 also reduced gliosis, as demonstrated by a decrease in Iba1-positive microglial cells and GFAP-positive astrocytes. CONCLUSION: Our data indicate that C18:0 GM3 primarily attenuates the TLR4-driven inflammatory cascade initiated by intrastriatal LPS, thereby secondarily preserving striatal dopaminergic terminals and improving motor deficits. Although these results highlight anti-inflammatory neuroprotection, additional studies are required to determine whether GM3 also modulates downstream Parkinson-specific processes such as α-synuclein aggregation or progressive neurodegeneration.
Role of astrocytic mu-opioid receptors of the ventrolateral periaqueductal gray in modulating anxiety-like responses.
Du Y, Zhang A, Li Z … +10 more , Zhao Y, Liu S, Wei C, Zheng Q, Qiao Y, Liu Y, Ren W, Han J, Liu Z, Gao F
Behav Brain Funct · 2025 Jul · PMID 40702536 · Full text
BACKGROUND: Mu-opioid receptors (MORs) are critical regulators mediating the modulation of several behavioral reactions, including analgesia, addiction, and sedation. Recent studies have reported that MORs are closely as...
BACKGROUND: Mu-opioid receptors (MORs) are critical regulators mediating the modulation of several behavioral reactions, including analgesia, addiction, and sedation. Recent studies have reported that MORs are closely associated with mood disorders or anxiety behaviors; however, the underlying neural mechanisms remain unclear. The periaqueductal gray (PAG), a key brain area, participates in the modulation of aversive emotional behaviors. MORs show a high expression in the ventrolateral PAG (vlPAG) region. This study explored the preliminary role of MORs expressed in the vlPAG in modulating emotional behaviors. RESULTS: Bilateral administration of DAMGO, an MOR-specific agonist, into the vlPAG of male mice elicited anxiety-like behaviors in elevated plus maze tests. This phenotype was reversed by conditional knockdown of astrocytic MORs. In contrast, glutamatergic or GABAergic MORs were not involved in vlPAG MOR-dependent anxiety-like behaviors. By using in vitro calcium imaging of vlPAG astrocytes and chemical genetic technologies, we found that vlPAG astrocytic MORs can promote astrocytic calcium signaling, which can efficiently induce anxiety-like behaviors. Accordingly, the interference of astrocytic calcium signaling by viral infection reversed vlPAG-dependent anxiety-like behaviors. CONCLUSION: Our findings demonstrated that vlPAG astrocytic, but not glutamatergic or GABAergic, MORs are involved in modulating emotional reactions, and these effects are accomplished by MOR-elicited astrocytic calcium signaling mechanisms. The present study provides a theoretical basis for treating emotional dysfunctions during MOR-targeted management.
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