Oanh T.P. Trinh , Andrew Ferns , Paapa Mensah-Kane , Bethany S. Zachariah , Nathalie Sumien
{"title":"Behavioral profiling of hyperbaric oxygen as an intervention for chemotherapy-related functional impairments in male and female mice","authors":"Oanh T.P. Trinh , Andrew Ferns , Paapa Mensah-Kane , Bethany S. Zachariah , Nathalie Sumien","doi":"10.1016/j.bbr.2025.115717","DOIUrl":"10.1016/j.bbr.2025.115717","url":null,"abstract":"<div><div>‘Chemobrain’ or chemotherapy-related cognitive impairment (CRCI) affects up to 75 % of cancer patients and survivors following chemotherapy treatments. Chemotherapy typically impairs multiple domains, including learning, memory, attention, executive function, and mood regulation, persisting for decades after treatment cessation and significantly diminishing cancer survivors’ quality of life. Despite its prevalence and long-term impact, effective interventions for CRCI remain limited. This study investigated the behavioral effects of hyperbaric oxygen (HBO) therapy on mice exposed to chemotherapy drugs methotrexate (MTX) and 5-fluorouracil (5-FU). Adult male and female C57BL/6 mice received intraperitoneal injections of either saline or chemotherapy (Low-dose: MTX 37.5 mg/kg and 5-FU 50 mg/kg; High-dose: MTX 70 mg/kg and 5-FU 100 mg/kg) once a week for three weeks. Concurrently, subsets of mice underwent daily HBO (2.4 ATA, 90 min) five days a week for three weeks. Animals’ health was evaluated weekly, and behavioral assessment of cognitive, motor, and affective functions was conducted post-treatment. Our results showed that chemotherapy, especially at high-dose, impaired spatial memory and navigation, avoidance learning, fear discrimination, and anxiety regulation differently between males and females. HBO significantly alleviated chemotherapy-induced avoidance learning impairment in both sexes and improved coordinated running capacity in high-dose treated males. However, HBO co-treatment increased spatial memory deficit in males and increased anxiety-like behaviors in females. In conclusion, although HBO had some nuanced effects on the various domains, some reversal of CRCI were observed. Therefore, HBO should be further studied and considered as a potential treatment for ‘chemobrain’.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115717"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535944","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":"Corrigendum to \"Perceptual regulation of ideal body shape in young women with body shame: An ERP study of cognitive reappraisal\" [Behav. Brain Res. 443 (2025) 115690].","authors":"Zhennan Liu, Yinying Hu, Haoyue Qian, Xiangping Gao","doi":"10.1016/j.bbr.2025.115713","DOIUrl":"https://doi.org/10.1016/j.bbr.2025.115713","url":null,"abstract":"","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":" ","pages":"115713"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537954","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}
Diya Flenaugh , Morgan Pride , Evelyn M. Chang , Alex Y. Chang , Lauren Bethea , Antoniette Maldonado-Devincci , Jian Han
{"title":"Short-term high-fat diet elevates oxidative stress in male but not female A53T mice without altering striatal dopaminergic markers","authors":"Diya Flenaugh , Morgan Pride , Evelyn M. Chang , Alex Y. Chang , Lauren Bethea , Antoniette Maldonado-Devincci , Jian Han","doi":"10.1016/j.bbr.2025.115715","DOIUrl":"10.1016/j.bbr.2025.115715","url":null,"abstract":"<div><div>High-fat diet (HFD) consumption influences the risk of Parkinson’s disease (PD), with effects varying based on exposure duration. This study examined the impact of a short-term, lard-based HFD on motor and anxiety-like behaviors, as well as dopaminergic markers, in a PD mouse model (A53T mice). One-month-old male and female A53T mice were fed either a control (10 % kcal from fat) or an HFD (45 % kcal from fat) diet for three months. Sex-specific differences in weight gain, behavior, and dopaminergic markers were assessed. <u>HFD-fed male mice gained significantly more weight than control males <u>(p < 0.0001),</u>whereas weight gain in females was less affected by diet. No significant dietary effects were observed on motor behaviors or dopaminergic markers, including α-synuclein, dopamine, dopamine receptor D2, dopamine transporter, and vesicular monoamine transporter 2. However, a significant sex effect was found for anxiety-like behavior. Additionally, oxidative stress was elevated in males compared to females and was further exacerbated by HFD in males.</u> These findings suggest that although short-term HFD did not impact motor behavior or dopaminergic markers, male mice were more susceptible to HFD-induced weight gain and oxidative stress than females.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115715"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549126","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}
Shuntaro Sugimoto, Misaki Yokoshi, Takumi Maruyama, Seiichiro Amemiya, Ichiro Kita
{"title":"Effects of acute treadmill running following administration of lipopolysaccharide on subsequent changes in microglial activation and depressive-like behavior in rats","authors":"Shuntaro Sugimoto, Misaki Yokoshi, Takumi Maruyama, Seiichiro Amemiya, Ichiro Kita","doi":"10.1016/j.bbr.2025.115718","DOIUrl":"10.1016/j.bbr.2025.115718","url":null,"abstract":"<div><div>The mechanisms underlying the beneficial effects of physical exercise on the brain, including its antidepressant properties, have yet to be fully elucidated. Recently, there has been growing interest that the beneficial effects of physical exercise may be related to its ability to reduce neuroinflammation by modulating microglial activation in the brain. However, no studies have investigated the relationship between microglial activation and depressive symptoms in the context of exercise intervention. The goal of the study was to assess if exercise would reduce depression-like behaviors and microglia activation induced by lipopolysaccharide (LPS). Here, we examined whether a bout of treadmill running (15 m/min, 30 min) performed 2 h after the administration of LPS (0.83 mg/mL/kg, i.p.) would affect subsequent changes in microglial activation and depressive-like behavior in rats. Microglial activation was assessed by alterations in microglial morphology (somatic cell size) in the dorsal raphe nucleus (DRN), hippocampal dentate gyrus (DG) and hypothalamic paraventricular nucleus (PVN), which were selected based on their involvement in stress regulation and the pathophysiology of depression, performing immunohistochemistry for ionized calcium-binding adapter molecule 1 (Iba1). In addition, we performed a forced swim test (FST) in the LPS-treated rats to assess the antidepressant effect of physical exercise on inflammation-induced depression. The increase of the somatic area of Iba1-positive cells in the DRN and DG at 24 h after LPS administration was significantly attenuated by a bout of acute and mild treadmill running performed 2 h after LPS administration. In addition, the LPS-induced increase of immobility time in the FST was significantly suppressed by the acute treadmill running. These results suggest that mild physical exercise can suppress microglia-induced neuroinflammation and exert an antidepressant effect against inflammation-induced depression.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115718"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523969","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":"Differential actions of ketamine on CA3-prelimbic and CA3-infralimbic connection responsivity depend on prior exposure to stress","authors":"Carlos M. Contreras , Ana G. Gutiérrez-García","doi":"10.1016/j.bbr.2025.115712","DOIUrl":"10.1016/j.bbr.2025.115712","url":null,"abstract":"<div><div>The present study explored the behavioral stressing action of a 15-min forced swim test (FST) session, changes in CA3-medial prefrontal cortex (mPFC) connection responsivity, and whether ketamine reverses such changes. Two groups of male Wistar rats were subjected to a 15-min FST session. Sixty minutes later, they were injected with either saline (stress [STR] SAL group) or ketamine (STR KET group). Twenty-four hours later, these two groups underwent an open field test (OFT) and a 5-min FST session. The other two groups received similar treatments (SAL group and KET group) without being subjected to the FST. In all four groups, single-unit extracellular recordings from the prelimbic (PL) and infralimbic (IL) regions of the mPFC were obtained while the CA3 hippocampal region was stimulated. Ketamine decreased the time spent immobile in the FST without altering behavior in the OFT. In the SAL group, CA3 stimulation produced an inhibitory response in the PL but a strong excitatory response in the IL. In the KET group, there were no changes in connection responsivity in the CA3-PL connection, but an inhibitory response was observed in the CA3-IL connection. Responsivity of the CA3-PL connection was similar between the STR KET and STR SAL groups. In the SAL group, CA3 stimulation produced an inhibitory response in the IL, which was accentuated in the STR SAL group. In the STR KET group, the inhibitory response was abolished. These findings indicate that the CA3-PL connection is sensitive to stress, independent of drug treatment, whereas the CA3-IL connection is sensitive to ketamine, but its action depends on prior stress exposure.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115712"},"PeriodicalIF":2.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510655","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":"Interplay between exercise and neuregulin in providing neuroprotection","authors":"Jyotsna Sharma , Abhimanyu Thakur , Manjari Rain , Radhika Khosla , Kalyan Maity , Gaurav Raj Mathur , Akshay Anand","doi":"10.1016/j.bbr.2025.115710","DOIUrl":"10.1016/j.bbr.2025.115710","url":null,"abstract":"<div><div>Exercise has been shown to have a positive impact on brain health including neuroprotective function. It has been demonstrated to increase the synthesis of neurotrophic factors, support neuronal survival, and improve neuroplasticity. Concurrently, neuregulin plays a vital role in the development, maintenance, and repair of both the central and peripheral nervous system. The link between exercise and neuregulin in mediating neuroprotection has been the subject of increased research to better understand the possible applications for the deterrence of neurodegenerative disorders. Understanding this link is of great interest because it has the potential to lead to new strategies for preventing or slowing the progression of neurodegenerative diseases. With an emphasis on exercise-induced neuregulin-mediated neuroprotection, this article reviews the literature on the neuroprotective effects of exercise and neuregulin. The synergistic effects of exercise and neuregulin on neuroprotection will be clarified and valuable insights will be gained from this review, with potential implications for the development of novel therapeutic strategies for neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Alzheimer's disease (AD) and Huntington’s disease (HD).</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115710"},"PeriodicalIF":2.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491095","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":"Comparative brain proteome analysis of an Indole Alkaloid of Kratom, Mitragynine and Kratom juice in rats","authors":"Sohaib Jumaah Owaid , Suleiman Yunusa , Lay-Harn Gam , Zurina Hassan","doi":"10.1016/j.bbr.2025.115709","DOIUrl":"10.1016/j.bbr.2025.115709","url":null,"abstract":"<div><div><em>Mitragyna speciosa,</em> commonly known as kratom, is a medicinal plant that is widely used for various medical conditions. The major alkaloid in kratom is mitragynine which binds partially to opioid receptors to produce opioid-like effects. In this study, we compared the effects of mitragynine various doses with kratom juice on neurobehavioral, neurochemical changes as well as calretinin protein expression. Sprague-Dawley rats were divided into ten groups (n = 6) and respectively received the following treatment: group 1 (20 % Tween 80), group 2 (morphine 10 mg/kg), groups 3–9, mitragynine graded doses (0.25, 0.5, 1, 5, 10, 15, and 30 mg/kg) and group 10 was given kratom juice (500 mg/kg). All the treatments were given as a single dosing and then for four consecutive days. On day 5, an open field test box was used for the assessment of behavioural parameters using global scoring. Whole brains were harvested and the effects of the treatments on some neurotransmitters related to addiction were determined using ELISA kits. Proteomic analysis was also conducted using two-dimensional gel electrophoresis and a western blot was conducted to determine the changes in the expression level of calretinin. Mitragynine but not kratom juice significantly increased some behavioural signs. Mitragynine doses above 5 mg/kg significantly increased dopamine, 5-HT, and GABA concentrations, whereas kratom juice only elevated GABA levels. Rat brain proteome analysis revealed that mitragynine significantly up-regulated calretinin. Western blot analysis shows that mitragynine but not kratom juice, significantly increased the expression level of calretinin. These findings suggest that kratom juice at the dose tested (500 mg/kg) may pose less risk of addiction compared to pure mitragynine at various doses.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115709"},"PeriodicalIF":2.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491902","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}
Li Hou , Ling Xin , Yuru Liu , Bin He , Cuige Shi , Yishu Yang
{"title":"Transcriptome sequencing and bioinformatics analysis of hippocampus in aged rats with cognitive decline","authors":"Li Hou , Ling Xin , Yuru Liu , Bin He , Cuige Shi , Yishu Yang","doi":"10.1016/j.bbr.2025.115711","DOIUrl":"10.1016/j.bbr.2025.115711","url":null,"abstract":"<div><div>Age-related cognitive decline poses significant challenges to healthy aging, yet its underlying molecular mechanisms remain poorly understood. In this study, we employed Morris Water Maze and hippocampal transcriptome analysis to investigate age-related cognitive decline in a rat model. Aged rats (RA) exhibited significant spatial memory deficits compared to young rats (RY). Transcriptome analysis identified 121 differentially expressed genes (DEGs) in the hippocampus of RA group compared with RY group, including 54 up-regulated and 67 down-regulated genes. The qRT-PCR validation revealed significant up-regulation of Cd74 and Cd4 expression, along with marked down-regulation of Col1a1, Col3a1, and Serpine1 expression in RA group compared to RY group. Bioinformatics analysis revealed these DEGs were enriched in the biological processes of chronic inflammation, loss of proteostasis, and extracellular matrix pathways. These findings suggest hippocampal transcriptomic alterations may contribute to cognitive aging, providing potential predictors for cognitive function and a foundation for exploring molecular mechanisms.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115711"},"PeriodicalIF":2.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481783","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}
Rosa H. Mulder , Bing Xu , Mónica López-Vicente , Marian H. Bakermans-Kranenburg , Marinus H. van IJzendoorn , Henning Tiemeier , Ryan L. Muetzel
{"title":"Brain structure and function and social exclusion reactivity in the Cyberball game","authors":"Rosa H. Mulder , Bing Xu , Mónica López-Vicente , Marian H. Bakermans-Kranenburg , Marinus H. van IJzendoorn , Henning Tiemeier , Ryan L. Muetzel","doi":"10.1016/j.bbr.2025.115707","DOIUrl":"10.1016/j.bbr.2025.115707","url":null,"abstract":"<div><div>Social exclusion or rejection is a universal stressor, and strong responses to rejection have been related to mental health issues. Previous studies linked rejection to concurrent brain activity in, amongst others, the insula or cingulo-operculum, areas related to pain processing. To date however, studies have only studied to the state of the brain <em>during</em> rejection, and not rejection in relation more stable brain characteristics. Identifying which brain areas are different among those that respond more to rejection could help us understand more of the biological underpinnings of rejection sensitivity and ultimately alleviate associated mental health issues. Here the relation between brain structure, resting-state functional connectivity and rejection reactivity <em>outside</em> of the MRI scanner was studied, in a multi-ethnic population-based sample of 1814 9-to-12-year-olds. Using the Cyberball paradigm, observed emotional facial expressions and self-reported feelings during peer rejection were measured. Stronger resting-state functional connectivity between the dorsal striatum, visual, and sensori-motor networks, and between the cingulo-operculum and dorsal attention network was related to negative emotional facial expressions during peer rejection (beta = 0.11–0.12). No associations were detected for self-reported reactions or brain structure. The dorsal striatum is related to automated behavior and functional connectivity between these and other networks may indicate why some children are more expressive in their reaction to rejection. Findings in the cingulo-operculum and dorsal attention network are in line with earlier studies, here suggesting that brain activity during rest is related to the risk of feeling ‘hurt’ when socially rejected.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115707"},"PeriodicalIF":2.6,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366269","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":"Low-grade chronic inflammatory stimulation alleviates α‑syn accumulation in Parkinson's disease by activating autophagy to promote neuronal survival in the Thy1-h[A30P]α-syn mouse model.","authors":"Min Yin, Yangbo Zhang, Zhijuan Cheng, Zhiping Wu, Qinghua Luo, Weiping Chen","doi":"10.1016/j.bbr.2025.115703","DOIUrl":"10.1016/j.bbr.2025.115703","url":null,"abstract":"<p><p>The impact of inflammation on Parkinson's disease (PD) development and progression varies based on factors such as the intensity, duration of inflammation, and the disease stage. Delving deeper into this aspect could unveil novel therapeutic opportunities for PD treatment. (Thy-1)-h[A30P]α-syn mice were used as PD animal models. Low-grade chronic inflammatory stimulation was applied by the treatment of lipopolysaccharide (LPS) or monophosphoryl lipid (MPL). RT-qPCR, western blotting, IHC, and IF staining were utilized to confirm the relative expression of targeted genes and proteins. Assay kits were used to determine the levels of Cathepsin B (CTSB) activities. The motor function of the mice was assessed by pole-climbing test and field test. Mild inflammatory stimulus activated microglia without elevating their secretion of inflammatory cytokines. This stimulation also induced activation of autophagy, and facilitated the degradation of α-syn in the midbrain by triggering the autophagy-lysosome pathway, thereby fostering neuron survival. Low-grade inflammatory stimulation promoted α-syn degradation via the autophagy-lysosome pathway. These findings offer new perspectives for the treatment of PD.</p>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":" ","pages":"115703"},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367850","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}