Behavioural Brain Research最新文献

{"title":"An unescapable looming threat paradigm for assessing anxiety-like responses in rats","authors":"Brittany L. Aguilar ,&nbsp;Jonathan Toib ,&nbsp;Ludise Malkova ,&nbsp;Patrick A. Forcelli","doi":"10.1016/j.bbr.2024.115296","DOIUrl":"10.1016/j.bbr.2024.115296","url":null,"abstract":"<div><div>Rapidly approaching visual stimuli (i.e. looming objects) are known to evoke unconditioned defense responses across species. In rodents, this threat reactivity repertoire includes freezing and fleeing behavior. Although components of the circuitry underlying unconditioned response to a looming threat have been elucidated, both a temporal characterization and drug effects on the freezing response have not yet been reported. Here, we describe a modified version of a looming threat task in which no escape route is available. In this task, we observed unconditioned freezing prior to, during, and after exposure to a looming threat stimulus. In Long Evans (LE) and Sprague-Dawley (SD) rats, we report looming stimulus-specific freezing response. We further explored the specificity and pharmacosensitivity of this response in male and female LE rats. Administration of a GABA-A receptor negative allosteric modulator (FG-7142) did not re-establish freezing in habituated animals; however, administration of a GABA-A receptor positive allosteric modulator (diazepam) in naïve LEs significantly reduced freezing during the post-looming period in a sex-dependent manner. Presentation of an unescapable looming stimulus results in freezing that extends beyond the acute threat exposure. Because freezing responses outlast the initial threat, and display only modest sensitivity to conventional anxiolytic therapy, this may represent a platform for screening agents in treatment-refractory anxiety.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"477 ","pages":"Article 115296"},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457064","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":"HINT1 promotes neuronal apoptosis and triggers schizophrenia-like behavior in rats","authors":"Yanhai Kang ,&nbsp;Li Sheng ,&nbsp;Jia Li","doi":"10.1016/j.bbr.2024.115297","DOIUrl":"10.1016/j.bbr.2024.115297","url":null,"abstract":"<div><div>This study aims to investigate the mechanism by which Histidine triad nucleotide-binding protein 1 (HINT1) promotes hippocampal neuronal apoptosis, triggering schizophrenia (SZ<strong>)-</strong>like behavior in rats. By establishing a rat SZ-like model, we assessed learning, memory, emotional response, and cognitive function through the Morris Water Maze, auditory startle response, and open field tests. HINT1 expression in the hippocampus was analyzed via RT-PCR and Western blot. We also created a HINT1 overexpression model in hippocampal neuronal cells to analyze its effects on cell proliferation and apoptosis. This analysis was conducted using the CCK-8 assay and flow cytometry, along with the quantification of apoptosis-related proteins and neurotrophic factors. Our findings indicated that the SZ-like model rats exhibited diminished learning and memory abilities, altered emotional reactions, and impaired cognitive functions, alongside a notable increase in HINT1 mRNA and protein levels. HINT1 overexpression was observed to inhibit hippocampal neuronal cell proliferation and promote apoptosis, with an increase in the expression of pro-apoptotic proteins and a decrease in neurotrophic factors. These results suggest HINT1's role in the onset and development of SZ-like behavior through its upregulation and induction of apoptosis in hippocampal neuronal cells, underlining its potential as a therapeutic target.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"477 ","pages":"Article 115297"},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457066","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":"Effect of chronic alcohol exposure and single-prolonged stress on conditioned fear behavior","authors":"Heyam K. Mayberry,&nbsp;Jennifer A. Rinker,&nbsp;L. Judson Chandler","doi":"10.1016/j.bbr.2024.115294","DOIUrl":"10.1016/j.bbr.2024.115294","url":null,"abstract":"<div><div>The present study investigated the impact of chronic intermittent ethanol (CIE) exposure and single-prolonged stress (SPS) on the acquisition of fear memories in both male and female Wistar rats. Adult rats were first subjected to CIE by vapor inhalation followed by SPS. Following a subsequent 8-day incubation period, the rats underwent a Pavlovian fear conditioning procedure (tone-shock pairings) followed by cued-tone extinction training, and then testing of extinction recall memory and fear renewal memory. In control animals that had not been exposed to either CIE or SPS, female rats exhibited significantly lower levels of freezing compared to male rats during tone-shock pairings. This lower level of freezing in female rats during conditioning was associated with an increased speed of movement compared to males. Also compared to males, female rats exhibited lower levels of fear extinction, recall, and renewal. Exposure to CIE, SPS, or CIE+SPS had no effect on freezing during the cued-conditioning, extinction, or extinction recall phases of the testing procedure in either sex. In fear renewal, CIE exposure decreased freezing in male but not female rats, while SPS increased freezing in female but not male rats. CIE exposure significantly reduced freezing during the fear renewal phase. Taken together, these results provide further evidence that male and female rats adopt different avoidance strategies for threat responding. These results also revealed that prior exposure to CIE, SPS, or CIE+SPS had minimal effects on threat responding using conditioned freezing as an indicator of fear responsivity.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"477 ","pages":"Article 115294"},"PeriodicalIF":2.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446292","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":"DNA methylation profiles of transgenerational rat hyperactivity primed by silver nanoparticles: Comparison with valproate model rats of autism","authors":"Masami Ishido ,&nbsp;Kouichi Higashi ,&nbsp;Hiroshi Mori ,&nbsp;Masaki Ueno ,&nbsp;Ken Kurokawa","doi":"10.1016/j.bbr.2024.115293","DOIUrl":"10.1016/j.bbr.2024.115293","url":null,"abstract":"<div><div>There is an increasing body of evidence suggesting that a single exposure to certain chemicals can have transgenerational effects, with the underlying mechanism believed to be epigenetic. However, it remains largely unknown whether psychiatric conditions like ADHD or autism, induced by environmental chemicals, can be inherited across generations. Pregnant rats were purchased from a commercial breeder. On the 7th day of gestation (E7), they were divided into two groups: one group was orally exposed to silver nanoparticles (AgNP; 4 mg/kg), while the control group received vehicle alone. The subsequent generation (F1) underwent spontaneous motor activity (SMA) measurements at 8–11 weeks of age. For breeding at 26 weeks of age, rats with higher SMA were selected from hyperactive litters, while untreated rats were randomly selected. This process was continued for four generations in both groups. The AgNP-primed rats at 4th generation displayed significantly higher SMA, 1.8 times greater than that of untreated rats. Intraperitoneal injection of valproic acid (150 mg/kg), an epigenetic modifier to 5-day-old rats causes adult hyperactivity (1.4-fold), suggesting that epigenetic modification contributes to rat hyperactivity. Global DNA methylation profiles in the mesencephalon were positively correlated in both groups of hyperactive rats. Furthermore, there were 7–8 common genes showing both hypermethylation and hypomethylation, which are involved in neuronal development, neuronal function, transcriptional activity, DNA binding activity, cell differentiation, ubiquitination processes, or histone modification, including Pax 6 and Mecp 2. Thus, it is most likely that rats retain hyperactivity through mesencephalic DNA methylation status across transgeneration.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"477 ","pages":"Article 115293"},"PeriodicalIF":2.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457065","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":"The effects of moderate alcohol and THC co-use during male and female rat adolescence on AKT-GSK3ß signaling in adulthood","authors":"Linyuan Shi ,&nbsp;Chan Young Choi ,&nbsp;Lauren K. Carrica ,&nbsp;Nu-Chu Liang ,&nbsp;Joshua M. Gulley","doi":"10.1016/j.bbr.2024.115292","DOIUrl":"10.1016/j.bbr.2024.115292","url":null,"abstract":"<div><div>Alcohol and cannabis are often taken in combination, and extensive co-use has been linked to enduring changes in cognitive and metabolic functioning. The underlying mechanisms for these effects are unclear, but we recently demonstrated that co-administration of ethanol and delta-9-tetrahydrocannbinol (THC) to adolescent rats caused lasting adaptations in GABA and glycogen synthase kinase 3ß (GSK3ß) signaling in the medial prefrontal cortex (mPFC). As a ubiquitous protein kinase, GSK3ß is downstream to the protein kinase B (also known as AKT) pathway that is activated by insulin receptor signaling in a main control center for metabolism and energy homeostasis, the mediobasal hypothalamus (MBH). Our goal here was to investigate if volitional co-use of low to moderate levels of ethanol and THC would impact the total and phosphorylated levels (p) of AKT and GSK3ß in the mPFC and MBH. Peri-adolescent Long Evans rats [postnatal day (P) 30–47] consumed 10 % ethanol, cookies laced with THC (3–10 mg/kg/day), both drugs, or vehicle controls. On P114, we modeled re-exposure to a behaviorally relevant dose of THC by challenging rats (i.p.) with 5 mg/kg THC (or vehicle) and sacrificed them 30 min later. Western blot analysis revealed that THC challenge increased pAKT and pGSK3ß compared to control similarly across all treatment groups, sexes, and brain regions; no effects on total levels of AKT or GSK3ß were found. Previously reported behavioral results from these rats showed no differences in working memory assessed in adulthood. Although future studies will be necessary to determine the role of exposure dose on drug-induced adaptations in AKT and GSK3ß signaling, the current findings suggest that moderate volitional co-use of alcohol and THC may not produce long-term deficits that persist into adulthood.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"476 ","pages":"Article 115292"},"PeriodicalIF":2.6,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441302","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":"Impact of feeding age on cognitive impairment in mice with Disrupted-In-Schizophrenia 1 (Disc1) mutation under a high sucrose diet","authors":"Jonghyuk Park ,&nbsp;Hiroko Shimbo ,&nbsp;Shoko Tamura ,&nbsp;Toshifumi Tomoda ,&nbsp;Takatoshi Hikida ,&nbsp;Haruo Okado ,&nbsp;Shinobu Hirai","doi":"10.1016/j.bbr.2024.115291","DOIUrl":"10.1016/j.bbr.2024.115291","url":null,"abstract":"<div><div>A combination of genetic predisposition and environmental factors contributes to the development of psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder. Previous studies using mouse models suggested that prolonged high sucrose intake during puberty can serve as an environmental risk factor for the onset of psychiatric disorders. However, the impact of both the duration and timing of high sucrose consumption during different developmental stages on pathogenesis remains poorly defined. We therefore investigated the effects of a long-term high sucrose diet on cognitive deficit, a core symptom of psychiatric disorders, using <em>Disrupted-in-Schizophrenia 1</em> locus-impairment heterozygous mutant (<em>Disc1</em>^<em>het</em>) mice as a model for genetic predisposition. First, <em>Disc1</em>^<em>het</em> mice and their littermate control (WT) were fed either a high sucrose diet or a control starch diet for nine weeks starting at weaning (postnatal day 24), and tested for cognitive performance in the object location test (OLT) and the novel object recognition test (NORT) (assessing spatial and recognition memory, respectively). Only <em>Disc1</em>^<em>het</em> mice on a high sucrose diet displayed deficits in OLT (p &lt; 0.0001), demonstrating impaired hippocampus-dependent spatial memory. This behavioral abnormality was accompanied by a decreased proportion of the high parvalbumin-expressing interneurons (High-PV neurons) in the ventral hippocampus, a cell type that regulates neural activity and a variety of learning and memory processes such as spatial and working memory. We further explored the critical developmental period for high sucrose intake to cause cognitive deficits in adulthood by comparing specific feeding periods during puberty (P24-P65) and post-puberty (P65-P90). Compared to those on a standard chow diet, high sucrose intake caused deficits in spatial memory in both WT and <em>Disc1</em>^<em>het</em> mice, with more pronounced effects in <em>Disc1</em>^het mice. In particular, <em>Disc1</em>^<em>het</em> mice on a sucrose diet during adolescence showed more pronounced cognitive deficit than those fed after adolescence. Our results suggest that adolescence is particularly vulnerable to nutritional environmental risk factors, and that high sucrose consumption may cause hippocampus-dependent memory deficits via decreased High-PV interneuron function when combined with Disc1-related genetic predisposition.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"476 ","pages":"Article 115291"},"PeriodicalIF":2.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438334","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":"The effect of creatinine level on amyloid-β and tau plasma concentrations in a cohort of Alzheimer’s disease patients without kidney disease","authors":"Francesco Motolese ,&nbsp;Davide Norata ,&nbsp;Gianmarco Iaccarino ,&nbsp;Elisabetta Sapio ,&nbsp;Fioravante Capone","doi":"10.1016/j.bbr.2024.115289","DOIUrl":"10.1016/j.bbr.2024.115289","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is pathologically characterized by the deposition of beta-amyloid and tau-protein. Blood biomarkers (BBM) might be employed for detecting these abnormal proteins in vivo. As the kidney is an important excretory organ, a decreased renal function might affect the clearance of BBM. In this study we aimed to assess the relationship between kidney function, the levels of BBM and cognitive impairment in a cohort of patients with a biological AD diagnosis without chronic kidney disease (CKD).</div></div><div><h3>Methods</h3><div>This is a retrospective cohort study on AD patients. Data regarding medical history at diagnosis (T0) were retrieved, together with the Mini-Mental State Examination (MMSE) score at T0 and after 6 months (T1). Cerebrospinal fluid and blood samples were collected and concentrations of Aβ42, Aβ40, t-Tau, and p-Tau181 were determined using commercially available kits. Kidney function was estimated through the 2021-CKD-EPI equation. To assess the effects of creatinine on our parameters of interest, we grouped patients into two groups –creatinine level &lt;0.8 mg/dl (LOW) or ≥0.8 mg/dl (HIGH).</div></div><div><h3>Results</h3><div>The median MMSE score decreased significantly between the two timepoints. When we assessed for differences in the parameters of interest between subgroups, we found that only Aβ42 plasma level was significantly different in the HIGH vs LOW group.</div></div><div><h3>Conclusion</h3><div>We found out that only Aβ42 plasma levels are influenced by kidney function, while the other AD biomarkers are not affected by creatinine levels or eGFR. Our findings are consistent with the hypothesis of renal clearance of Aβ isoforms.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"477 ","pages":"Article 115289"},"PeriodicalIF":2.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457070","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":"The effect of Amantadine on recovery, postoperative cognitive dysfunction and pain after propofol anesthesia in mice","authors":"Burçin Alaçam ,&nbsp;Şeyma Nur Başarır ,&nbsp;Ayça Taş Tuna ,&nbsp;Onur Palabıyık ,&nbsp;Hüseyin Çakıroğlu","doi":"10.1016/j.bbr.2024.115290","DOIUrl":"10.1016/j.bbr.2024.115290","url":null,"abstract":"<div><h3>Introduction</h3><div>Postoperative cognitive dysfunction (POCD) encompasses a spectrum of cognitive impairments following surgery, attributed to disruptions in brain homeostasis. The pathogenesis involves glutamate toxicity, GABA receptor dysfunction, and alterations in NMDA and AMPA receptors. This study aimed to investigate the impact of pre-anesthetic amantadine administration on postoperative recovery time, POCD, and stress-related pain levels when combined with propofol anesthesia.</div></div><div><h3>Methods</h3><div>Twenty-four adult male BALB/C mice were divided into four groups: Control, Propofol, Amantadine, and Amantadine+Propofol. Amantadine and propofol doses were administered intraperitoneally based on previous literature. Recovery time, pain levels (assessed via tail pinch and hot plate tests), cognitive functions (evaluated through Morris Water Maze), and locomotor activity (measured via Open Field Test) were recorded.</div></div><div><h3>Results</h3><div>Amantadine administration significantly reduced recovery time from propofol anesthesia, prolonged pain perception, and preserved cognitive functions compared to propofol alone. The time spent in the target quadrant in the Morris Water Maze was significantly longer in groups receiving amantadine. Additionally, the distance covered until finding the platform was significantly shorter in the propofol-only group.</div></div><div><h3>Discussion</h3><div>Amantadine's neuroprotective effects, attributed to its antagonistic action on glutamate and NMDA receptors, mitigate the detrimental effects of propofol on cognitive function and pain perception. This study highlights the potential of combining amantadine with propofol to enhance postoperative outcomes.</div></div><div><h3>Conclusion</h3><div>Amantadine administration before propofol anesthesia positively influenced postoperative recovery, cognitive function preservation, and stress-related pain perception in mice. These findings suggest a potential therapeutic strategy to mitigate POCD and pain associated with surgery.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"477 ","pages":"Article 115290"},"PeriodicalIF":2.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446293","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":"Exploring neural efficiency in spatial cognition: A comparative study of 3D visual stimuli in virtual reality across STEM and non-STEM fields","authors":"Raimundo da Silva Soares Jr. ,&nbsp;Amanda Yumi Ambriola Oku ,&nbsp;Cândida S.F. Barreto ,&nbsp;João Ricardo Sato","doi":"10.1016/j.bbr.2024.115288","DOIUrl":"10.1016/j.bbr.2024.115288","url":null,"abstract":"<div><div>Spatial cognition plays a crucial role in our daily lives. The relationship between spatial abilities and mathematical performance is well-established, with visuospatial training offering significant benefits in academic STEM (Science, Technology, Engineering, and Mathematics) disciplines. Developing visuospatial training requires an objective evaluation of spatial cognition and consideration of various 3D displays. This study aims to compare the neural efficiency of STEM and non-STEM individuals during mental rotation tasks (MRT) in 3D and 2.5D conditions (pseudo 3D) using virtual reality (VR). For that, we propose a novel integrative assessment of spatial cognition by combining a cost-effective VR headset and functional near-infrared spectroscopy (fNIRS). Overall, the findings reveal that STEM individuals exhibit greater neural efficiency in the dorsolateral prefrontal cortex (PFC) while solving MRT in a VR environment compared to their non-STEM counterparts. Additionally, the study shows that there is no significant difference in performance between 3D and 2.5D stimuli, suggesting that both conditions are equally suitable for MRT in VR. One possible explanation is that immersive VR reduces the distinctions between 3D models and 2.5D images, considering MRT scores and PFC activity. This research underscores the practicality and relevance of using VR and fNIRS to evaluate visuospatial tasks and the potential to identify distinct student learning profiles and enhance spatial skills. Furthermore, it highlights the potential of 2.5D stimuli as a cost-effective alternative for learning applications in VR. Here, we demonstrated that modeling the same task in 3D and 2.5D conditions can compare how humans interact with visuospatial tests, providing insights into applying VR devices to develop spatial skills.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"477 ","pages":"Article 115288"},"PeriodicalIF":2.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457069","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":"The antidepressant effect of Komagataella pastoris KM 71 H in maternal separation mice model mediated by the microbiota-gut-brain axis","authors":"Paloma T. Birmann ,&nbsp;Airton Sinott ,&nbsp;Giuliana P. Zugno ,&nbsp;Rafael R. Rodrigues ,&nbsp;Fabricio R. Conceição ,&nbsp;Fernanda S.S. Sousa ,&nbsp;Tiago Collares ,&nbsp;Fabiana K. Seixas ,&nbsp;Lucielli Savegnago","doi":"10.1016/j.bbr.2024.115287","DOIUrl":"10.1016/j.bbr.2024.115287","url":null,"abstract":"<div><h3>Background</h3><div>The intestinal microbiota plays a fundamental role in maintaining host health, especially during childhood, a critical period for its establishment. Early life stress can lead to shifts in gut microbiota composition, thus increasing the risk of major depressive disorder (MDD) in adulthood. The supplementation with probiotics restores intestinal permeability and the health of gut microbial communities, therefore being potential study targets for the treatment of MDD. In this sense, the yeast <em>Komagataella pastoris</em> was reported as a promising probiotic with antidepressant effect.</div></div><div><h3>Methods</h3><div>Hence, the present study aims to investigate this effect in mice submitted to maternal separation (MS) 3 h per day from PND2 to PND14. Adult mice and mothers were treated with <em>K. pastoris</em> KM71H (8 log UFC.g⁻¹/per animal, i.g.) or PBS (500 µl, i.g.) for 14 days. After behavioral tests, the animals were euthanized, followed by hippocampi and intestines removal for biochemical analysis.</div></div><div><h3>Results</h3><div>On behavioral tests, <em>K. pastoris</em> KM71H treatment reduced the immobility time in TST of adult mice and increased the grooming activity in splash test of adult mice and mothers induced by MS. The probiotic treatment restored plasma corticosterone levels and <em>glucocorticoid receptor</em> expression in hippocampi, alongside nitrate/nitrite levels and superoxide dismutase activity in intestine, in addition to reducing reactive species levels in both structures. Moreover, it also normalized the fecal pH and water content of feces.</div></div><div><h3>Conclusion</h3><div>Thus, we conclude that <em>K. pastoris</em> KM71H is a promising therapeutic strategy for the treatment of MDD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"476 ","pages":"Article 115287"},"PeriodicalIF":2.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405991","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}