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RAGE/AP-1/OTR signaling pathway in rat hippocampus DG involved in CUS induced depressive-like behaviors 大鼠海马 DG 中的 RAGE/AP-1/OTR 信号通路参与了 CUS 诱导的抑郁样行为。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-03-14 DOI: 10.1016/j.bbr.2025.115540
Xuemei Li , Xin Wang , Lifen Xue, Lan Luo, Lingxiao Hu, Wengao Jiang
There has been a growing body of evidence indicating that the oxytocin (OT) system plays a significant role in the neurophysiology of chronic stress-related mood disorders in recent years. However, the precise alterations for the OT system in response to chronic stress and the underlying mechanism remains unclear. The present study demonstrated that chronic unpredictable stress (CUS) resulted in a reduction in the expression of RAGE and OTR, as well as an inhibition of AP-1 phosphorylation. RAGE knockdown in hippocampus DG induced depressive-like behaviors, down-regulated the OTR protein and mRNA levels, and reduced the AP-1 phosphorylation. The administration of OT via the nasal route reversed the depressive-like behaviors induced by RAGE knockdown, increased the levels of BDNF expression and AP-1 phosphorylation. On the other hand, RAGE over-expression in the hippocampus DG resisted the effects of CUS on depression-like behaviors, AP-1 phosphorylation, and OTR expression. These finding suggested that RAGE signaling pathway is involved in CUS induced depressive-like behaviors at least partially by regulating OTR expression.
{"title":"RAGE/AP-1/OTR signaling pathway in rat hippocampus DG involved in CUS induced depressive-like behaviors","authors":"Xuemei Li ,&nbsp;Xin Wang ,&nbsp;Lifen Xue,&nbsp;Lan Luo,&nbsp;Lingxiao Hu,&nbsp;Wengao Jiang","doi":"10.1016/j.bbr.2025.115540","DOIUrl":"10.1016/j.bbr.2025.115540","url":null,"abstract":"<div><div>There has been a growing body of evidence indicating that the oxytocin (OT) system plays a significant role in the neurophysiology of chronic stress-related mood disorders in recent years. However, the precise alterations for the OT system in response to chronic stress and the underlying mechanism remains unclear. The present study demonstrated that chronic unpredictable stress (CUS) resulted in a reduction in the expression of RAGE and OTR, as well as an inhibition of AP-1 phosphorylation. RAGE knockdown in hippocampus DG induced depressive-like behaviors, down-regulated the OTR protein and mRNA levels, and reduced the AP-1 phosphorylation. The administration of OT via the nasal route reversed the depressive-like behaviors induced by RAGE knockdown, increased the levels of BDNF expression and AP-1 phosphorylation. On the other hand, RAGE over-expression in the hippocampus DG resisted the effects of CUS on depression-like behaviors, AP-1 phosphorylation, and OTR expression. These finding suggested that RAGE signaling pathway is involved in CUS induced depressive-like behaviors at least partially by regulating OTR expression.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115540"},"PeriodicalIF":2.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639520","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}
引用次数: 0
Music Boosts the Recovery of Attention after Mental Fatigue in Healthy Young Male Subjects: A Human Auditory Event-Related Potential Study. 音乐促进健康年轻男性受试者精神疲劳后注意力的恢复:人类听觉事件相关电位研究》。
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-03-13 DOI: 10.1016/j.bbr.2025.115539
Zhiding Wang, Wenhao Xu, Cheng Zhang, Chaoyue Zhang, Yinji Liu, Pinhong Chen, Gencheng Han, Lubin Wang

Daily life faces continuous cognitive tasks. Several methods could lessen cognitive fatigue including music. To find out how music functions in recovering cognitive fatigue, twenty-seven participants were randomly assigned to the rest group (N=12) and the music group (N=15). To evaluate the effects of Mozart K488 music on attention function after a continuous cognitively demanding task. Participants completed subjective questionnaires and the contingent negative variation (CNV) task before fatigue, after fatigue, and after the rest/musical intervention. EEG and ECG data were also collected during the experiment. The results showed that 5min of Mozart K488 music resulted in improved CNV task performance in the musical intervention group. For EEG data, recoveries of the initial CNV and terminal CNV amplitude in Cz and CPz electrodes were observed and compared with the values after Mental Fatigue, which music increased the iCNV and tCNV. Alpha-ERD was lower after listening to music than after resting. Moreover, during music playing, compared to other brain regions the EEG alpha power of participants was significantly high in the central frontal region. This study demonstrates a short-term musical intervention can effectively boost the recovery of attention after Mental Fatigue.

日常生活面临着持续的认知任务。有几种方法可以减轻认知疲劳,其中包括音乐。为了了解音乐在恢复认知疲劳方面的作用,27 名参与者被随机分配到休息组(12 人)和音乐组(15 人)。评估莫扎特 K488 音乐对连续认知要求任务后注意力功能的影响。参与者分别在疲劳前、疲劳后和休息/音乐干预后完成主观问卷和或然负变异(CNV)任务。实验期间还收集了脑电图和心电图数据。结果显示,5 分钟的莫扎特 K488 音乐可提高音乐干预组的 CNV 任务表现。在脑电图数据方面,观察到 Cz 和 CPz 电极的初始 CNV 和末端 CNV 振幅的恢复情况,并与精神疲劳后的数值进行比较,发现音乐增加了 iCNV 和 tCNV。听音乐后的α-ERD 低于休息后的α-ERD。此外,在音乐播放过程中,与其他脑区相比,参与者额叶中央区的脑电图阿尔法功率明显较高。这项研究表明,短期音乐干预可以有效促进精神疲劳后注意力的恢复。
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引用次数: 0
Comparative analysis of analgesic and anxiolytic effects of alcoholic extracts from Eryngium billardieri and Urtica dioica in a rat model of chronic pain
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-03-12 DOI: 10.1016/j.bbr.2025.115537
Mohammad Hosein Naeimi Ghahroodi , Zahra Bahari , Mahdi Mashhadi Akbar Boojar

Objective

The treatment of neuropathic pain is crucial, as it not only alleviates physical discomfort but also reduces anxiety associated with pain, ultimately enhancing the quality of life for affected individuals. This study investigates the protective effects of hydro-alcoholic extracts from Eryngium billardieri (Er) and Urtica dioica (Ur) on neuropathic pain and anxiety responses in an animal model.

Methods

40 male Wistar rats were used to investigate neuropathy induced by the chronic constriction injury (CCI) model. Animals were divided into five experimental groups (N = 8): [sham], [CCI], [CCI+Er], [CCI+Ur], and [CCI+Imipramine]. Er and Ur were administered orally for 30 days, starting on the day of surgery. Behavioral tests, including acetone for cold allodynia, the elevated plus maze for anxiety-like behaviors, and the open field for innate anxiety, were conducted on day −1 (before CCI) and on days 2, 4, 6, 14, 21, and 30. Data were analyzed by one-way analysis of variance test, and P < 0.05 was considered significant.

Results

Neuropathic surgery resulted in cold allodynia and anxiety-like behaviors throughout the experiment as compared to the sham. Er extract significantly decreased both cold allodynia and anxiety-like behaviors in the CCI group. However, Ur extract only significantly reduced cold allodynia (and not anxiety-like behaviors). Additionally, there was no difference between the analgesic effects of Er and Ur extracts.

Conclusions

These findings support the use of Er as a potential comprehensive treatment for neuropathic pain and anxiety symptoms. Future research should focus on exploring the specific mechanisms behind these effects and the potential for synergistic treatments to improve outcomes for individuals suffering from neuropathy.
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引用次数: 0
Neuroprotective effect of nano-carboxymethyl chitosan from Doryteuthis sibogae against rotenone-induced Parkinson’s disease in the zebrafish model
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-03-08 DOI: 10.1016/j.bbr.2025.115523
Srinivasan Palaniselvam , Vignesh Narasimman , R. Vijayashree , Saravanan Ramachandran
This study investigates the neuroprotective effects of N-carboxymethyl chitosan (N-CMC) against rotenone (ROT)-induced Parkinson's disease (PD) in a zebrafish (ZF) model. In vivo experiments revealed that ROT-exposed ZF larvae exhibited reduced locomotor activity, increased edge preference, and impaired touch response, while N-CMC treatment significantly improved these behavioral parameters. The reactive oxygen species (ROS) levels in ROT-exposed larvae were elevated (37.75 %) but decreased with N-CMC treatment (30.28 %). Apoptosis was also reduced from 38.87 % in ROT-exposed larvae to 16.52 % with N-CMC treatment. In vitro studies using the N2A cell line confirmed N-CMC’s neuroprotective effects. In adult ZF, ROT exposure decreased locomotion, and N-CMC treatment reversed these effects, as demonstrated through ToxTrac analysis. Novel Tank and Light/Dark tests showed significant behavioral improvements with N-CMC. Neurotransmitter analysis indicated increased dopamine, GABA, and glutamate levels in ROT-exposed ZF, which were moderated with N-CMC treatment. Gene expression analysis of gap43, syn2a, and tuba1b showed upregulation in ROT-exposed ZF, while N-CMC treatment downregulated these genes. Antioxidant assays demonstrated that ROT decreased SOD, CAT, and GSH levels in the brain, while N-CMC treatment increased these antioxidant levels by 1.3-fold, 7.5-fold, and 1.3-fold, respectively. Histopathology revealed neuronal degeneration in ROT-exposed ZF brains, but N-CMC treatment protected the neuronal loss. This study is the first to explore the neuroprotective and antioxidant properties of N-CMC in a ZF model, indicating its potential therapeutic benefits over conventional ROT-based treatments for PD.
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引用次数: 0
The relationship between neuropsychiatric disorders and aging: A review on telomere length, oxidative stress, and inflammation
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-03-08 DOI: 10.1016/j.bbr.2025.115528
Tala Solh , Şule Coşkun Cevher
Aging is the group of time-independent changes that occur in an organism and that ultimately end in death. The relationship between aging and neuropsychiatric disorders is complex. Not only does the incidence of several neuropsychiatric disorders rise with age, but also these disorders are linked with premature mortality and are even thought to be syndromes of accelerated biological aging. Oxidative stress, inflammation and telomere length are factors commonly used to assess biological aging. The purpose of this review is to sum up the existing information about the state of those factors in schizophrenia, depression, bipolar disorder and anxiety disorders, and to summarize the effects of treatment on telomere length in patients with those neuropsychiatric disorders. The main focus, however, is on telomere length seeing the highly controversial study results on this biomarker in neuropsychiatric disorders. There is no scientific consensus on the state of those factors in the mentioned neuropsychiatric disorders or on the effects of treatment on telomere length, thus further research is needed where confounding variables are controlled. Regarding telomere length, it is highly important to explore whether short telomeres lead to the development of neuropsychiatric disorders or vice versa, as it carries huge clinical potential.
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引用次数: 0
Role of the neuropeptide S receptor 1 rs324981 polymorphism in modulating emotionality and cognitive flexibility: Insights from a gene-edited mouse model
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-03-08 DOI: 10.1016/j.bbr.2025.115530
Virginie Rappeneau , Ann-Marie Tobinski , Leonardo Miguel Caisachana Guevara , Neele Meyer , Kay Jüngling , Chadi Touma
The neuropeptide S (NPS) and its receptor (NPSR1) are involved in various physiological processes, including arousal, sleep, anxiety, memory, and stress responses in rodents. Recent attention has focused on the association between the NPS/NPSR1 system and stress-related disorders, particularly involving a specific single nucleotide polymorphism (SNP) in the NPSR1 gene (rs324981). This SNP causes an amino acid change at position 107 in the protein, reducing NPSR1 signalling potency; however, its effects on behavioural, cognitive, and physiological aspects relevant to stress-related disorders remain unclear.
Addressing this topic, we characterized the behavioural phenotype of a gene-editing mouse model, expressing either the murine/ancestral NPSR1-I107 variant or the human NPSR1-N107 variant. Both, male and female mice underwent a comprehensive behavioural test battery assessing arousal, exploratory and anxiety-related behaviour under varying levels of novelty stress. Moreover, cognitive functions were evaluated with a special focus on cognitive flexibility using the Attentional Set Shifting Task (ASST). Additionally, markers of behavioural and endocrine stress reactivity were assessed as well as changes in body weight and body composition.
Our results showed that NPSR1-N107 mice displayed increased anxiety-related behaviour compared to NPSR1-I107 mice, with no significant differences in arousal, exploratory behaviour or hormonal stress responses. However, NPSR1-N107 mice also exhibited better rule-reversal learning in the ASST, indicating enhanced cognitive flexibility. These findings provide clear evidence for a role of the NPSR1 rs324981 SNP in regulating emotionality and cognitive flexibility, underscoring the potential of the NPSR1-I107N mouse model for further elucidating the molecular mechanisms underlying stress-related disorders.
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引用次数: 0
White matter tract involvement in anarchic hand syndrome following stroke: Diffusion tensor imaging study
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-03-08 DOI: 10.1016/j.bbr.2025.115529
Jihee Park , Woo-Suk Tae , Sekwang Lee , Sung-Bom Pyun
Anarchic Hand Syndrome (AHS) is a rare neurological disorder characterized by involuntary, purposeful hand movements. AHS can also result from damage to the corpus callosum (CC), intra-hemispheric tracts, or descending tracts, but its precise causes remain unclear. This study aimed to identify the white matter tracts associated with AHS development using the automated reconstruction of 42 tracts from diffusion tensor imaging (DTI).
We included three female AHS patients with anterior cerebral arterial (ACA) infarctions. Additionally, we enrolled 20 age-matched control subjects and six patients with ACA infarctions but without AHS symptoms (N-AHS group) for comparison. DTI was conducted in AHS, N-AHS, and control groups. Fractional anisotropy (FA) and volume values were extracted from the DTI datasets of participants using TRActs Constrained by UnderLying Anatomy (TRACULA) technique.
The AHS group showed lower FA values of the CC body (parietal and temporal section), right arcuate fasciculus (AF), corticospinal tract, extreme capsule, inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus than the control group. However, these tracts exhibited no significant difference between N-AHS and control groups. Similarly, the volume value in the genu of CC in the AHS group was lower than controls, but not in other tracts.
Our results suggests that the extensive CC lesion, especially in the posterior parietal and temporal section of CC body, and damage to intra-hemispheric tracts (AF and ILF), is associated with the development of AHS. These results involved in AHS and underscore the significance of considering a more complex network disruption, involving various white matter tracts beyond CC for understanding this syndrome.
{"title":"White matter tract involvement in anarchic hand syndrome following stroke: Diffusion tensor imaging study","authors":"Jihee Park ,&nbsp;Woo-Suk Tae ,&nbsp;Sekwang Lee ,&nbsp;Sung-Bom Pyun","doi":"10.1016/j.bbr.2025.115529","DOIUrl":"10.1016/j.bbr.2025.115529","url":null,"abstract":"<div><div>Anarchic Hand Syndrome (AHS) is a rare neurological disorder characterized by involuntary, purposeful hand movements. AHS can also result from damage to the corpus callosum (CC), intra-hemispheric tracts, or descending tracts, but its precise causes remain unclear. This study aimed to identify the white matter tracts associated with AHS development using the automated reconstruction of 42 tracts from diffusion tensor imaging (DTI).</div><div>We included three female AHS patients with anterior cerebral arterial (ACA) infarctions. Additionally, we enrolled 20 age-matched control subjects and six patients with ACA infarctions but without AHS symptoms (N-AHS group) for comparison. DTI was conducted in AHS, N-AHS, and control groups. Fractional anisotropy (FA) and volume values were extracted from the DTI datasets of participants using TRActs Constrained by UnderLying Anatomy (TRACULA) technique.</div><div>The AHS group showed lower FA values of the CC body (parietal and temporal section), right arcuate fasciculus (AF), corticospinal tract, extreme capsule, inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus than the control group. However, these tracts exhibited no significant difference between N-AHS and control groups. Similarly, the volume value in the genu of CC in the AHS group was lower than controls, but not in other tracts.</div><div>Our results suggests that the extensive CC lesion, especially in the posterior parietal and temporal section of CC body, and damage to intra-hemispheric tracts (AF and ILF), is associated with the development of AHS. These results involved in AHS and underscore the significance of considering a more complex network disruption, involving various white matter tracts beyond CC for understanding this syndrome.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115529"},"PeriodicalIF":2.6,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595842","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}
引用次数: 0
Embryonic Zebrafish Irritant-evoked Hyperlocomotion (EZIH) as a high-throughput behavioral model for nociception
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-03-06 DOI: 10.1016/j.bbr.2025.115526
Amelia A. Bunnell , Erin M. Marshall , Summer K. Estes , Monica C. Deadmond , Sandra Loesgen , James A. Strother
Behavioral models have served a key role in understanding nociception, the sensory system by which animals detect noxious stimuli in their environment. Developing zebrafish (Danio rerio) are a powerful study organism for examining nociceptive pathways, given the vast array of genetic, developmental, and neuroscience tools available for these animals. However, at present there are few widely-adopted behavioral models for nociception in developing zebrafish. This study examines the locomotor response of hatching-stage zebrafish embryos to dilute solutions of the noxious chemical and TRPA1 agonist allyl isothiocyanate (AITC). At this developmental stage, AITC exposure induces a robust uniphasic hyperlocomotion response. This behavior was thoroughly characterized by determining the effects of pre-treatment with an array of pharmacological agents, including anesthetics, TRPA1 agonists/antagonists, opioids, NSAIDs, benzodiazepines, SSRIs, and SNRIs. Anesthetics suppressed the response to AITC, pre-treatment with TRPA1 agonists induced hyperlocomotion and blunted the response to subsequent AITC exposures, and TRPA1 antagonists and the opioid buprenorphine tended to reduce the response to AITC. The behavioral responses of zebrafish embryos to a noxious chemical were minimally affected by the other pharmacological agents examined. The feasibility of using this behavioral model as a screening platform for drug discovery efforts was then evaluated by assaying a library of natural product mixtures from microbial extracts and fractions. Overall, our results indicate that irritant-evoked locomotion in embryonic zebrafish is a robust behavioral model for nociception with substantial potential for examining the molecular and cellular pathways associated with nociception and for drug discovery efforts.
{"title":"Embryonic Zebrafish Irritant-evoked Hyperlocomotion (EZIH) as a high-throughput behavioral model for nociception","authors":"Amelia A. Bunnell ,&nbsp;Erin M. Marshall ,&nbsp;Summer K. Estes ,&nbsp;Monica C. Deadmond ,&nbsp;Sandra Loesgen ,&nbsp;James A. Strother","doi":"10.1016/j.bbr.2025.115526","DOIUrl":"10.1016/j.bbr.2025.115526","url":null,"abstract":"<div><div>Behavioral models have served a key role in understanding nociception, the sensory system by which animals detect noxious stimuli in their environment. Developing zebrafish (<em>Danio rerio</em>) are a powerful study organism for examining nociceptive pathways, given the vast array of genetic, developmental, and neuroscience tools available for these animals. However, at present there are few widely-adopted behavioral models for nociception in developing zebrafish. This study examines the locomotor response of hatching-stage zebrafish embryos to dilute solutions of the noxious chemical and TRPA1 agonist allyl isothiocyanate (AITC). At this developmental stage, AITC exposure induces a robust uniphasic hyperlocomotion response. This behavior was thoroughly characterized by determining the effects of pre-treatment with an array of pharmacological agents, including anesthetics, TRPA1 agonists/antagonists, opioids, NSAIDs, benzodiazepines, SSRIs, and SNRIs. Anesthetics suppressed the response to AITC, pre-treatment with TRPA1 agonists induced hyperlocomotion and blunted the response to subsequent AITC exposures, and TRPA1 antagonists and the opioid buprenorphine tended to reduce the response to AITC. The behavioral responses of zebrafish embryos to a noxious chemical were minimally affected by the other pharmacological agents examined. The feasibility of using this behavioral model as a screening platform for drug discovery efforts was then evaluated by assaying a library of natural product mixtures from microbial extracts and fractions. Overall, our results indicate that irritant-evoked locomotion in embryonic zebrafish is a robust behavioral model for nociception with substantial potential for examining the molecular and cellular pathways associated with nociception and for drug discovery efforts.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115526"},"PeriodicalIF":2.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584457","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}
引用次数: 0
Genetic determinants of longitudinal behavioural trajectories in rare conditions: The case of fragile X syndrome
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-03-05 DOI: 10.1016/j.bbr.2025.115527
Lydia Cartwright , Gaia Scerif , Chris Oliver , Andrew Beggs , Joanne Stockton , Lucy Wilde , Hayley Crawford
Despite being a monogenic condition, individual variability in the phenotypic profile of fragile X syndrome (FXS) is substantial, with behavioural outcomes differing in severity and frequency. Existing studies have revealed that common variation in 5-HTTLPR (serotonin) and COMT (dopamine) single nucleotide polymorphisms (SNPs) is associated with behavioural variation in FXS when measured cross-sectionally. However, the associations between SNPs and longitudinal behavioural trajectories in FXS remain unknown. This study explored relationships between three SNPs, selected a priori (5-HTTLPR, COMT and monoamine oxidase A (MAOA)), and trajectories of clinically relevant behaviours in 42 males with FXS. Autistic characteristics, property destruction, aggression, stereotyped behaviour, self-injury, repetitive behaviour, and mood/interest and pleasure were measured at two time points across three years via a series of standardised informant questionnaires. DNA was extracted from saliva samples and a combination of PCR and TaqMan genotyping was performed for genetic confirmation of FXS, and COMT, 5-HTTLPR and MAOA analyses. Results revealed that males with FXS with AA COMT genotype were less likely to display persistent stereotyped behaviour compared to AG or GG genotypes. Participants with the S/S 5-HTTLPR genotype displayed a steeper decline in repetitive and stereotyped behaviours compared to the L/S or L/L genotypes. Participants with the three-repeat MAOA genotype demonstrated a steeper decline in communication skills over three years compared to those with four repeats. This study documents the association between common genetic variation and behavioural trajectories in males with FXS. Results suggest specific SNPs play an important role in longitudinal behavioural patterns in FXS. This work may facilitate an understanding of individual trajectories for people with FXS, and, therefore, support future tailored interventions.
{"title":"Genetic determinants of longitudinal behavioural trajectories in rare conditions: The case of fragile X syndrome","authors":"Lydia Cartwright ,&nbsp;Gaia Scerif ,&nbsp;Chris Oliver ,&nbsp;Andrew Beggs ,&nbsp;Joanne Stockton ,&nbsp;Lucy Wilde ,&nbsp;Hayley Crawford","doi":"10.1016/j.bbr.2025.115527","DOIUrl":"10.1016/j.bbr.2025.115527","url":null,"abstract":"<div><div>Despite being a monogenic condition, individual variability in the phenotypic profile of fragile X syndrome (FXS) is substantial, with behavioural outcomes differing in severity and frequency. Existing studies have revealed that common variation in 5-HTTLPR (serotonin) and COMT (dopamine) single nucleotide polymorphisms (SNPs) is associated with behavioural variation in FXS when measured cross-sectionally. However, the associations between SNPs and longitudinal behavioural trajectories in FXS remain unknown. This study explored relationships between three SNPs, selected a priori (5-HTTLPR, COMT and monoamine oxidase A (MAOA)), and trajectories of clinically relevant behaviours in 42 males with FXS. Autistic characteristics, property destruction, aggression, stereotyped behaviour, self-injury, repetitive behaviour, and mood/interest and pleasure were measured at two time points across three years via a series of standardised informant questionnaires. DNA was extracted from saliva samples and a combination of PCR and TaqMan genotyping was performed for genetic confirmation of FXS, and COMT, 5-HTTLPR and MAOA analyses. Results revealed that males with FXS with AA COMT genotype were less likely to display persistent stereotyped behaviour compared to AG or GG genotypes. Participants with the S/S 5-HTTLPR genotype displayed a steeper decline in repetitive and stereotyped behaviours compared to the L/S or L/L genotypes. Participants with the three-repeat MAOA genotype demonstrated a steeper decline in communication skills over three years compared to those with four repeats. This study documents the association between common genetic variation and behavioural trajectories in males with FXS. Results suggest specific SNPs play an important role in longitudinal behavioural patterns in FXS. This work may facilitate an understanding of individual trajectories for people with FXS, and, therefore, support future tailored interventions.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115527"},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578004","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}
引用次数: 0
Environmental enrichment reverses cognitive impairments and hippocampus tissue loss without altering the redox state in rats exposed to severe chronic hyperhomocysteinemia
IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Pub Date : 2025-03-05 DOI: 10.1016/j.bbr.2025.115522
E.F. Sanches , T.M. dos Santos , M.B. do Carmo , A.V.S. Carvalho , O.V. Ramires Junior , S.V. Sizonenko , C.A. Netto , A.T.S. Wyse

Introduction

Classical homocystinuria is a genetic disease caused by partial or total deficiency of cystathionine-β synthase (CβS) enzyme activity, ultimately leading to brain alterations and early atherosclerotic disease. Currently, there is no cure for the disease and the treatments consist in reducing homocysteine levels through diet, however not all patients respond to therapy. Due to its ability to increase neurotrophins production and decrease oxidative stress in the brain, environmental enrichment (EE) has been used with success as an adjuvant non-pharmacological therapy for CNS disorders. Here, we investigated the effects of 4 weeks enriched environment in a severe chronic chemically-induced model of hyperhomocysteinemia (HHCY) in Wistar rats.

Methods

Animals of both sexes were subjected to homocysteine administration subcutaneously (12 h intervals) from day 6 of life (P6) to P28. After this period, animals were continuously exposed to the enriched environment (or standard cages) for 30 days. Animals were tested for cognition and locomotor abilities and hippocampi were collected for the assessment of oxidative stress and histological damage.

Results

Animals in the HHCY group showed impaired learning in the reference memory assessment in the Morris water maze with no effects in the novel objects recognition test. HHCY did not impair locomotion in the open field nor in the horizontal ladder task. HHCY rats presented decreased hippocampal volume reversed by EE. Enrichment was also able to reverse cognitive impairments in the spatial memory, improve coordination in the ladder walking and recognition memory in the NOR test. HHCY altered redox balance, with no protective effects of EE.

Conclusions

Due to its benefits and no side effects reported in literature, EE can be suggested as potential complimentary therapy to improve memory and motricity impairments in homocystinuric patients, however the mechanisms involved in this neuroprotection needs further investigation.
{"title":"Environmental enrichment reverses cognitive impairments and hippocampus tissue loss without altering the redox state in rats exposed to severe chronic hyperhomocysteinemia","authors":"E.F. Sanches ,&nbsp;T.M. dos Santos ,&nbsp;M.B. do Carmo ,&nbsp;A.V.S. Carvalho ,&nbsp;O.V. Ramires Junior ,&nbsp;S.V. Sizonenko ,&nbsp;C.A. Netto ,&nbsp;A.T.S. Wyse","doi":"10.1016/j.bbr.2025.115522","DOIUrl":"10.1016/j.bbr.2025.115522","url":null,"abstract":"<div><h3>Introduction</h3><div>Classical homocystinuria is a genetic disease caused by partial or total deficiency of cystathionine-β synthase (CβS) enzyme activity, ultimately leading to brain alterations and early atherosclerotic disease. Currently, there is no cure for the disease and the treatments consist in reducing homocysteine levels through diet, however not all patients respond to therapy. Due to its ability to increase neurotrophins production and decrease oxidative stress in the brain, environmental enrichment (EE) has been used with success as an adjuvant non-pharmacological therapy for CNS disorders. Here, we investigated the effects of 4 weeks enriched environment in a severe chronic chemically-induced model of hyperhomocysteinemia (HHCY) in Wistar rats.</div></div><div><h3>Methods</h3><div>Animals of both sexes were subjected to homocysteine administration subcutaneously (12 h intervals) from day 6 of life (P6) to P28. After this period, animals were continuously exposed to the enriched environment (or standard cages) for 30 days. Animals were tested for cognition and locomotor abilities and hippocampi were collected for the assessment of oxidative stress and histological damage.</div></div><div><h3>Results</h3><div>Animals in the HHCY group showed impaired learning in the reference memory assessment in the Morris water maze with no effects in the novel objects recognition test. HHCY did not impair locomotion in the open field nor in the horizontal ladder task. HHCY rats presented decreased hippocampal volume reversed by EE. Enrichment was also able to reverse cognitive impairments in the spatial memory, improve coordination in the ladder walking and recognition memory in the NOR test. HHCY altered redox balance, with no protective effects of EE.</div></div><div><h3>Conclusions</h3><div>Due to its benefits and no side effects reported in literature, EE can be suggested as potential complimentary therapy to improve memory and motricity impairments in homocystinuric patients, however the mechanisms involved in this neuroprotection needs further investigation.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"485 ","pages":"Article 115522"},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584459","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}
引用次数: 0
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Behavioural Brain Research
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