{"title":"Glucocorticoid alleviates hypothalamic nerve injury via remodeling HPA axis homeostasis in stressed rats","authors":"","doi":"10.1016/j.bbr.2024.115223","DOIUrl":"10.1016/j.bbr.2024.115223","url":null,"abstract":"<div><p>Excessive stress can exceed the adjustment ability of body and cause injury and dysfunction, while elucidation of the mechanism and prevention measures of stress-related injury are still insufficient. The present study was to observe the effect of glucocorticoid (GC) on stress-induced hypothalamic nerve injury and elucidate the potential mechanism. The present study intended to establish a chronic restraint stress rat model for follow-up study. Open field test and elevated plus maze test were used to observe behavioral changes of stress rats; Enzyme-linked immunosorbent assay (ELISA) was used to detect changes in the levels of hypothalamus-pituitary-adrenal (HPA) axis-related hormones and inflammatory factors in hypothalamus; toluidine blue staining was used to observe pathological changes of hypothalamus. The results showed that stress rats showed obvious anxiety-like behaviors, the levels of HPA axis-related hormones and inflammatory factors showed abnormal fluctuations, and morphological results showed significant nerve injury in hypothalamus. Low-dose GC treatment significantly improved behavioral changes, alleviated hypothalamic nerve injury, and restored hypothalamic levels of inflammatory factors, serum levels of GC, corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH) and GC level in adrenal cortex of stressed rats, while GC receptor (GR) inhibitor, CRH receptor inhibitor, and adrenalectomy reversed the ameliorative effects of low-dose GC. Our study clarified that low-dose GC can restore stress coping ability by reshaping the homeostasis of the HPA axis, thus alleviating behavioral abnormalities and hypothalamic nerve injury in stressed rats.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"AQP4 is upregulated in schizophrenia and Its inhibition attenuates MK-801-induced schizophrenia-like behaviors in mice","authors":"","doi":"10.1016/j.bbr.2024.115220","DOIUrl":"10.1016/j.bbr.2024.115220","url":null,"abstract":"<div><h3>Background</h3><p>The pathophysiology and molecular mechanisms of schizophrenia (SCZ) remain unclear, and the effective treatment resources are still limited. The goal of this study is to identify the expression of AQP4 in SCZ patients and explore whether AQP4 inhibition could ameliorate schizophrenia-like behaviors and its mechanisms.</p></div><div><h3>Methods</h3><p>Microarray datasets of PFC compared with healthy control were searched in the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were analyzed with the GEO2R online tool. The Venny online tool and metascape online software were used to identify common abnormally expressed genes and conduct cell type signature enrichment analysis. SCZ mouse models were induced with MK-801, an NMDA receptor antagonist (intraperitoneal injection, 0.1 mg/kg/day for 7 days), and C6 cell models were treated with 100 μM MK-801. RT-qPCR, Western Blotting, and immunofluorescence were employed to determine the expression of <em>AQP4,</em> proinflammatory cytokines, and GFAP. Open field tests and social interaction tests were performed to evaluate the schizophrenia-like behaviors.</p></div><div><h3>Results</h3><p>Bioinformatics analysis identified upregulation of AQP4 in the PFC of SCZ patients compared with healthy controls. Cell type signature enrichment analysis showed that all three DEGs lists were strongly enriched in the FAN EMBRYONIC CTX ASTROCYTE 2 category. Upregulation of <em>AQP4</em> was also observed in MK-801-treated C6 cells and the PFC of MK-801-induced SCZ mouse model. Moreover, AQP4 inhibition with TGN-020 (an inhibitor of AQP4) improved anxiety-like behavior and social novelty preference defects in MK-801-treated mice. AQP4 inhibition also reduced the expression of <em>IL-1β, IL-6,</em> and <em>TNF-α</em> in MK-801-treated C6 cells and mouse model.</p></div><div><h3>Conclusions</h3><p>AQP4 is upregulated in the PFC of SCZ patients compared with healthy controls. AQP4 inhibition could alleviate the anxiety-like behavior and social novelty defects in MK-801-treated mice, this may be due to the role of AQP4 in the regulation of the expression of proinflammatory cytokines.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Frontal EEG alpha asymmetry predicts foreign language anxiety while speaking a foreign language","authors":"","doi":"10.1016/j.bbr.2024.115216","DOIUrl":"10.1016/j.bbr.2024.115216","url":null,"abstract":"<div><p>Engaging in dialog requires interlocutors to coordinate sending and receiving linguistic signals to build a discourse based upon interpretations and perceptions interconnected with a range of emotions. Conversing in a foreign language may induce emotions such as anxiety which influence the quality communication. The neural processes underpinning these interactions are crucial to understanding foreign language anxiety (FLA). Electroencephalography (EEG) studies reveal that anxiety is often displayed via hemispheric frontal alpha asymmetry (FAA). To examine the neural mechanisms underlying FLA, we collected self-reported data on the listening and speaking sections of the Second language skill specific anxiety scale (L2AS) over behavioral, cognitive, and somatic domains and recorded EEG signals during participation in word chain turn-taking activities in first (L1, Chinese) and second (L2, English) languages. Regression analysis showed FAA for the L2 condition was a significant predictor primarily of the behavioral and somatic domains on the L2AS speaking section. The results are discussed along with implications for improving communication during L2 interactions.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166432824003723/pdfft?md5=0be1218225e44981e880a35b7bc466d7&pid=1-s2.0-S0166432824003723-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhancing spatial memory and pattern separation: Long-term effects of stimulant treatment in individuals with ADHD","authors":"","doi":"10.1016/j.bbr.2024.115211","DOIUrl":"10.1016/j.bbr.2024.115211","url":null,"abstract":"<div><p>This study explores the under-researched domain of long-term stimulant treatment in children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD). The necessity for extended treatment duration, often accompanied by safety concerns and side effects leading to treatment discontinuation, underscores the significance of this investigation. Concurrently, comparative studies have revealed adverse impacts on vulnerable regions within the hippocampal formation, accompanied by behavioral perturbations. We employed computerized tests and virtual reality to assess spatial memory, pattern separation, and object recognition memory in a cohort of children diagnosed with ADHD receiving stimulant treatment. We compared their performance to a group of neurotypical peers. Our findings indicate that the ADHD group exhibited a lower performance in spatial memory, pattern separation, and object recognition memory than ND group. Intriguingly, a positive relationship emerged between the duration of stimulant treatment and performance in these variables. Notably, this improvement was not immediate to MPH treatment but becomes significant after 24 months of treatment. In contrast to previous comparative investigations, our study did not reveal a detrimental impact on spatial navigation, object recognition memory, or pattern separation, despite the known interplay of these cognitive processes with the hippocampal formation. These results shed new light on the nuanced effects of stimulant treatment in ADHD, underscoring the need for a more comprehensive understanding of long-term treatment outcomes.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016643282400367X/pdfft?md5=bf014b636bd64f145c503bd6057d865b&pid=1-s2.0-S016643282400367X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inflammatory injury induces pain sensitization that is expressed beyond the site of injury in male (and not in female) mice","authors":"","doi":"10.1016/j.bbr.2024.115215","DOIUrl":"10.1016/j.bbr.2024.115215","url":null,"abstract":"<div><p>Pain is a crucial protective mechanism for the body. It alerts us to potential tissue damage or injury and promotes the avoidance of harmful stimuli. Injury-induced inflammation and tissue damage lead to pain sensitization, which amplifies responses to subsequent noxious stimuli even after an initial primary injury has recovered. This phenomenon, commonly referred to as hyperalgesic priming, was investigated in male and female mice to determine whether it is specific to the site of previous injury. We used 10<span><math><mrow><mi>μ</mi><mi>l</mi></mrow></math></span> of 50 % Freund's complete adjuvant (CFA) administered to the left hind paw as a model of peripheral injury. Both male and female mice exhibited robust site-specific mechanical hypersensitivity after CFA, which resolved within one-week post-injection. After injury resolution, only male CFA-primed mice showed enhanced and prolonged mechanical sensitivity in response to a chemical challenge or a single 0.5 mA electric footshock. Among CFA-primed male mice, shock-induced mechanical hypersensitivity was expressed in both the left (previously injured) and the right (uninjured) hind paws, suggesting a pivotal role for altered centralized processes in the expression of pain sensitization. These findings indicate that pain history regulates sensory responses to subsequent mechanical and chemical pain stimuli in a sex-specific manner—foot-shock-induced hyperalgesic priming expression among male mice generalized beyond the initial injury site.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166432824003711/pdfft?md5=6a8dd19a7e24fd98c42bcb27c7baf54e&pid=1-s2.0-S0166432824003711-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Heavy metals exposure and Alzheimer’s disease: Underlying mechanisms and advancing therapeutic approaches","authors":"","doi":"10.1016/j.bbr.2024.115212","DOIUrl":"10.1016/j.bbr.2024.115212","url":null,"abstract":"<div><p>Heavy metals such as lead, cadmium, mercury, and arsenic are prevalent in the environment due to both natural and anthropogenic sources, leading to significant public health concerns. These heavy metals are known to cause damage to the nervous system, potentially leading to a range of neurological conditions including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and attention-deficit hyperactivity disorder (ADHD). The present study examines the complex relationship between heavy metal exposure and AD, focusing on the underlying mechanisms of toxicity and potential therapeutic approaches. This review article highlights how these metals can impair brain function through mechanisms such as oxidative stress, inflammation, and neurotransmitter disruption, ultimately contributing to neurodegenerative diseases like AD. It also addresses the challenges in diagnosing heavy metal-induced cognitive impairments and emphasizes the need for further research to explore effective treatment strategies and preventive measures against heavy metal exposure.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of combined postweaning social isolation and ketamine administration on schizophrenia-like behaviour in male Sprague Dawley rats","authors":"","doi":"10.1016/j.bbr.2024.115214","DOIUrl":"10.1016/j.bbr.2024.115214","url":null,"abstract":"<div><p>The pathophysiology behind negative and cognitive symptoms of schizophrenia is not well understood, thus limiting the effectiveness of treatment on these symptoms. Developing reliable animal model of schizophrenia is vital to advance our understanding on the neurobiological basis of the disorder. Double hit is used to refer to the use of two schizophrenia inducing interventions viz ketamine exposure and social isolation. In this study we aim to investigate the robustness of double hit model of schizophrenia in inducing negative and cognitive symptoms of schizophrenia. On postnatal day (PND) 23, thirty-two male Sprague Dawley rats were randomly grouped into four equal groups as follows: group housed + saline (GH), group housed + ketamine (GHK), isolated + saline (SI), and isolated + ketamine (SIK). A single ketamine dose (16 mg/kg) was administered 3 times a week for four weeks. Isolated animals were housed singly throughout the study. The following behavioural tests were carried out: elevated plus maze, three chamber social interaction, resident intruder tests, and novel object recognition (NOR). The SIK group exhibited high anxiety levels, with increased ACTH, corticosterone and norepinephrine concentration when compared to the other groups. The SIK animals also presented with reduced social interaction and decreased oxytocin concentration. SIK rats were more aggressive towards a juvenile intruder but had low testosterone concentration. The SIK group or double hit model showed impaired visual learning and memory and increased expression of proinflammatory cytokines. This suggest that the double hit model is more robust in inducing negative and cognitive symptoms of schizophrenia than each treatment alone.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016643282400370X/pdfft?md5=654d08d4b64f8e3dadd556b82b07fab1&pid=1-s2.0-S016643282400370X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correlation between compulsive behaviors and plastic changes in the dendritic spines of the prefrontal cortex and dorsolateral striatum of male rats","authors":"","doi":"10.1016/j.bbr.2024.115199","DOIUrl":"10.1016/j.bbr.2024.115199","url":null,"abstract":"<div><p>Obsessive-compulsive disorder (OCD) is a mental affliction characterized by compulsive behaviors often manifested in intrusive thoughts and repetitive actions. The quinpirole model has been used with rats to replicate compulsive behaviors and study the neurophysiological processes associated with this pathology. Several changes in the dendritic spines of the medial prefrontal cortex (mPFC) and dorsolateral striatum (DLS) have been related to the occurrence of compulsive behaviors. Dendritic spines regulate excitatory synaptic contacts, and their morphology is associated with various brain pathologies. The present study was designed to correlate the occurrence of compulsive behaviors (generated by administering the drug quinpirole) with the morphology of the different types of dendritic spines in the mPFC and DLS. A total of 18 male rats were used. Half were assigned to the experimental group, the other half to the control group. The former received injections of quinpirole, while the latter rats were injected with physiological saline solution, for 10 days in both cases. After the experimental treatment, the quinpirole rats exhibited all the parameters indicative of compulsive behavior and a significant correlation with the density of stubby and wide neckless spines in both the mPFC and DLS. Dendritic spines from both mPFC and DLS neurons showed plastic changes correlatively with the expression of compulsive behavior induced by quinpirole. Further studies are suggested to evaluate the involvement of glutamatergic neurotransmission in the neurobiology of OCD.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dopaminergic manipulations affect the modulation and meta-modulation of movement speed: Evidence from two pharmacological interventions","authors":"","doi":"10.1016/j.bbr.2024.115213","DOIUrl":"10.1016/j.bbr.2024.115213","url":null,"abstract":"<div><p>A body of research implicates dopamine in the average speed of simple movements. However, naturalistic movements span a range of different shaped trajectories and rarely proceed at a single constant speed. Instead, speed is reduced when drawing “corners” compared to “straights” (i.e., speed modulation), and the extent of this slowing down is dependent upon the global shape of the movement trajectory (i.e., speed meta-modulation) – for example whether the shape is an ellipse or a rounded square. At present, it is not known how (or whether) dopaminergic function controls continuous changes in speed during movement execution. The current paper reports effects on these kinematic features of movement following two forms of dopamine manipulation: Study One highlights movement differences in individuals with PD both ON and OFF their dopaminergic medication (N = 32); Study Two highlights movement differences in individuals from the general population on haloperidol (a dopamine receptor blocker, or “antagonist”) and placebo (N = 43). Evidence is presented implicating dopamine in speed, speed modulation and speed meta-modulation, whereby low dopamine conditions are associated with reductions in these variables. These findings move beyond vigour models implicating dopamine in average movement speed, and towards a conceptualisation that involves the modulation of speed as a function of contextual information.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166432824003693/pdfft?md5=d8d451c224a94fc43e64f9705004c04d&pid=1-s2.0-S0166432824003693-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Empirical examination of working memory performance and its neural correlates in relation to delay discounting in two large samples","authors":"","doi":"10.1016/j.bbr.2024.115217","DOIUrl":"10.1016/j.bbr.2024.115217","url":null,"abstract":"<div><p>The neurobiological basis of working memory and delay discounting are theorized to overlap, but few studies have empirically examined these relations in large samples. To address this, we investigated the association of neural activation during an fMRI N-Back working memory task with delay discounting area, as well as in- and out-of-scanner working memory measures. These analyses were conducted in two large task fMRI datasets, the Human Connectome Project and the Adolescent Brain Cognitive Development Study. Although in- and out-of-scanner working memory performance were significantly associated with N-back task brain activation regions, contrary to our hypotheses, there were no significant associations between working memory task activation and delay discounting scores. These findings call into question the extent of the neural overlap in delay discounting and working memory and highlight the need for more investigations directly interrogating overlapping and distinct brain regions across cognitive neuroscience tasks.</p></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166432824003735/pdfft?md5=1684a52f705b1d3cdc89adbbbf6adb66&pid=1-s2.0-S0166432824003735-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}