Authors:Yue-Ming Zhang, Ru-Meng Wei, Meng-Ying Zhang, Kai-Xuan Zhang, Jing-Ya Zhang, Shi-Kun Fang, Yi-Jun Ge, Xiao-Yi Kong, Gui-Hai Chen, Xue-Yan Li Abstract: Maternal exposure to inflammation may represent a major risk factor for neuropsychiatric disorders with associated cognitive dysfunction in offspring in later life. Growing evidence has suggested that resveratrol exerts a beneficial effect on cognitive impairment via its anti-inflammatory and antioxidant properties and by ameliorating synaptic dysfunction. However, how resveratrol affects maternal immune activation-induced cognitive dysfunction and the underlying mechanisms are unclear. In the present study, pregnant dams were given an intraperitoneal injection of lipopolysaccharide (LPS; 50 μg/kg) on gestational day 15. Subsequently, the offspring mice were treated or not with resveratrol (40 mg/kg) from postnatal day (PND) 60 to PND 88. Male offspring were selected for the evaluation of cognitive function using the Morris water maze test. The hippocampal levels of pro-inflammatory cytokines were examined by ELISA. The mRNA and protein levels of sirtuin-1 (SIRT1), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95), and synaptophysin (SYP) were determined by RT-qPCR and western blot, respectively. The results showed that male offspring mice exposed to LPS in utero exhibited learning and memory impairment. Additionally, the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were increased while those of SIRT1, BDNF, PSD-95, and SYP were decreased in male offspring of LPS-treated mothers. Treatment with resveratrol reversed cognitive impairment and attenuated the increase in the levels of pro-inflammatory cytokines induced by maternal immune activation in the offspring mice. Furthermore, resveratrol reversed the deleterious effects of maternal immune activation on SIRT1, BDNF, PSD-95, and SYP levels in the hippocampus. Collectively, our results suggested that resveratrol can effectively improve learning and memory impairment induced by maternal immune activation via the modulation of inflammation and synaptic dysfunction. PubDate: 2023-11-22T00:00:00Z
Authors:Brooke H. Kohn, Zehua Cui, Margo A. Candelaria, Stacy Buckingham-Howes, Maureen M. Black, Tracy Riggins Abstract: Early adversities, including prenatal drug exposure (PDE) and a negative postnatal emotional caregiving environment, impact children’s long-term development. The protracted developmental course of memory and its underlying neural systems offer a valuable framework for understanding the longitudinal associations of pre- and postnatal factors on children with PDE. This study longitudinally examines memory and hippocampal development in 69 parent–child dyads to investigate how the early caregiving emotional environment affects children with PDE’s neural and cognitive systems. Measures of physical health, drug exposure, caregiver stress, depression, and distress were collected between 0 and 24 months At age 14 years, adolescents completed multiple measures of episodic memory, and at ages 14 and 18 years, adolescents underwent magnetic resonance imaging (MRI) scans. Latent constructs of episodic memory and the caregiving environment were created using Confirmatory Factor Analysis. Multiple regressions revealed a negative emotional caregiving environment during infancy was associated with poor memory performance and smaller left hippocampal volumes at 14 years. Better memory performance at 14 years predicted larger right hippocampal volume at 18 years. At 18 years, the association between the emotional caregiving environment and hippocampal volume was moderated by sex, such that a negative emotional caregiving environment was associated with larger left hippocampal volumes in males but not females. Findings suggest that the postnatal caregiving environment may modulate the effects of PDE across development, influencing neurocognitive development. PubDate: 2023-11-20T00:00:00Z
Authors:Sandford Zeng, Elin F. B. McLaughlin, Aishwarya Ramesh, Sara E. Morrison Abstract: Adolescence is a time of heightened risk-taking across species. Salient audiovisual cues associated with rewards are a common feature of gambling environments and have been connected to increased risky decision-making. We have previously shown that, in adult male rats, sign tracking – a behavioral measure of cue reactivity – predicts an individual’s propensity for suboptimal risky choices in a rodent gambling task (rGT) with win-paired cues. However, adolescents perform less sign tracking than adult animals, suggesting that they are less cue-reactive than adults in some circumstances. Therefore, we investigated the performance of adolescent male rats on the rGT with win cues and examined its relationship with their sign-tracking behavior. We found that adolescents make more risky choices and fewer optimal choices on the rGT compared with adults, evidence of the validity of the rGT as a model of adolescent gambling behavior. We also confirmed that adolescents perform less sign tracking than adults, and we found that, unlike in adults, adolescents’ sign tracking was unrelated to their risk-taking in the rGT. This implies that adolescent risk-taking is less likely than that of adults to be driven by reward-related cues. Finally, we found that adults trained on the rGT as adolescents retained an adolescent-like propensity toward risky choices, suggesting that early exposure to a gambling environment may have a long-lasting impact on risk-taking behavior. PubDate: 2023-11-20T00:00:00Z
Authors:Steven P. Gargano, Melody G. Santos, Sydney M. Taylor, Irene Pastis Abstract: The intricate neural pathways involved in obsessive-compulsive disorder (OCD) affect areas of our brain that control executive functioning, organization, and planning. OCD is a chronic condition that can be debilitating, afflicting millions of people worldwide. The lifetime prevalence of OCD in the US is 2.3%. OCD is predominantly characterized by obsessions consisting of intrusive and unwanted thoughts, often with impulses that are strongly associated with anxiety. Compulsions with OCD encompass repetitive behaviors or mental acts to satisfy their afflicted obsessions or impulses. While these factors can be unique to each individual, it has been widely established that the etiology of OCD is complex as it relates to neuronal pathways, psychopharmacology, and brain chemistry involved and warrants further exploration. PubDate: 2023-11-16T00:00:00Z
Authors:Xueqian Ma, Beatrice Schildknecht, Adrian C. Steiner, Irmgard Amrein, Martina Nigri, Giulia Bramati, David P. Wolfer Abstract: The IntelliCage allows automated testing of cognitive abilities of mice in a social home cage environment without handling by human experimenters. Restricted water access in combination with protocols in which only correct responses give access to water is a reliable learning motivator for hippocampus-dependent tasks assessing spatial memory and executive function. However, water restriction may negatively impact on animal welfare, especially in poor learners. To better comply with the 3R principles, we previously tested protocols in which water was freely available but additional access to sweetened water could be obtained by learning a task rule. While this purely appetitive motivation worked for simple tasks, too many mice lost interest in the sweet reward during more difficult hippocampus-dependent tasks. In the present study, we tested a battery of increasingly difficult spatial tasks in which water was still available without learning the task rule, but rendered less attractive either by adding bitter tasting quinine or by increasing the amount of work to obtain it. As in previous protocols, learning of the task rule provided access to water sweetened with saccharin. The two approaches of dual motivation were tested in two cohorts of female C57BL/6 N mice. Compared to purely appetitive motivation, both novel protocols strongly improved task engagement and increased task performance. Importantly, neither of the added disincentives had an adverse impact on liquid consumption, health status or body weight of the animals. Our results show that it is possible to refine test protocols in the IntelliCage so that they challenge cognitive functions without restricting access to water. PubDate: 2023-11-16T00:00:00Z
Authors:Jie Bai, Jia-Quan Wei, Qian Tian, Fen Xue, Wen Zhang, Hong He Abstract: IntroductionElectroacupuncture (EA) is a beneficial physiotherapy approach for addressing neuropsychiatric disorders. Nevertheless, the impact of EA on the gut microbiome in relation to anxiety disorders remains poorly understood.MethodsTo address this gap, we conducted a study using a chronic restraint stress (CRS) mouse model to investigate the anti-anxiety outcome of EA and its influence on gut microbiota. Our research involved behavioral tests and comprehensive sequencing of full-length 16S rRNA microbiomes.ResultsOur findings revealed that CRS led to significant anxiety-like behaviors and an imbalance in the gut microbiota. Specifically, we identified 13 species that exhibited changes associated with anxiety-like behaviors. Furthermore, EA partially alleviated both behaviors related to anxiety and the dysbiosis induced by CRS.DiscussionIn summary, this study sheds light on the alterations in gut microbiota species resulting from CRS treatment and brings new light into the connection between EA’s anti-anxiety effects and the gut microbiota. PubDate: 2023-11-16T00:00:00Z
Authors:Laura Herrera-Isaza, Santiago Zárate-Guerrero, Karen Corredor, Ángela Gómez-Fonseca, Guillermo Escobar-Cornejo, Fernando P. Cardenas Abstract: IntroductionChronic use of various compounds can have long-lasting effects on animal behavior, and some of these effects can be influenced by the environment. Many environmental enrichment protocols have the potential to induce behavioral changes.AimThe aim of the present study was to investigate how environmental enrichment can mitigate the effects of chronic methylphenidate consumption on the behavior of Wistar rats.MethodsThe animals were housed for 20 days under either an environmental enrichment protocol (which included tubes of different shapes) or standard housing conditions. After seven days, half of the rats received 13 days of oral administration of methylphenidate (2 mg/kg). After seven days, the rats underwent behavioral tests, including the elevated plus maze (anxiety), open field (locomotion), object-in-place recognition test (spatial memory), and a test for social interaction (social behavior).ResultsThe results showed that the enriched environmental condition reversed the enhanced time in the open arms of the elevated plus maze induced by methylphenidate (F[1,43] = 4.275, p = 0.045). Methylphenidate also enhanced exploratory rearing in the open field (F[1,43] = 4.663, p = 0.036) and the time spent in the open area of the open field (H[3] = 8.786, p = 0.032). The enriched environment mitigated the inhibition of social interaction with peers induced by methylphenidate (H[3] = 16.755, p PubDate: 2023-11-14T00:00:00Z
Authors:Dana Bell, Vaughn J. Waldron, P. Leon Brown Abstract: IntroductionClinically relevant sex differences have been noted in a number of affective, behavioral, cognitive, and neurological health disorders. Midbrain dopamine neurons are implicated in several of these same disorders and consequently are under investigation for their potential role in the manifestation of these sex differences. The lateral habenula exerts significant inhibitory control over dopamine neuronal firing, yet little is known about sex differences in this particular neurocircuit.MethodsWe performed in vivo, single unit, extracellular recordings of dopamine neurons in female and male anesthetized rats in response to single pulse stimulation of the lateral habenula. In addition, we assessed baseline firing properties of lateral habenula neurons and, by immunochemical means, assessed the distribution of estrogen receptor alpha cells in the lateral habenula.ResultsHabenula-induced inhibition of dopamine neuronal firing is reduced in female rats relative to male rats. In addition, male rats had a higher prevalence of rebound excitation. Furthermore, the firing pattern of lateral habenula neurons was less variable in female rats, and female rats had a higher density of estrogen receptor alpha positive cells in the lateral habenula.DiscussionWe found that the dopamine neuronal response to habenular stimulation is both qualitatively and quantitatively different in female and male rats. These novel findings together with reports in the contemporary literature lead us to posit that the sex difference in dopamine inhibition seen here relate to differential firing properties of lateral habenula neurons resulting from the presence of sex hormones. Further work is needed to test this hypothesis, which may have implications for understanding the etiology of several mental health disorders including depression, schizophrenia, and addiction. PubDate: 2023-11-13T00:00:00Z
Authors:Erin K. Nagy, Jonna M. Leyrer-Jackson, Lauren E. Hood, Amanda M. Acuña, M. Foster Olive Abstract: Drugs of abuse activate neuroimmune signaling in addiction-related regions of the brain, including the prefrontal cortex (PFC) which mediates executive control, attention, and behavioral inhibition. Traditional psychostimulants including methamphetamine and cocaine are known to induce PFC inflammation, yet the effects of synthetic cathinone derivatives are largely unexplored. In this study, we examined the ability of repeated binge-like intake of the pyrovalerone cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV) to alter cytokine profiles in the PFC. Male and female rats were allowed to intravenously self-administer MDPV (0.05 mg/kg/infusion) or saline as a control under conditions of prolonged binge-like access, consisting of three 96 h periods of drug access interspersed with 72 h of forced abstinence. Three weeks following cessation of drug availability, PFC cytokine levels were assessed using antibody arrays. Employing the unsupervised clustering and regression analysis tool CytoMod, a single module of co-signaling cytokines associated with MDPV intake regardless of sex was identified. With regards to specific cytokines, MDPV intake was positively associated with PFC levels of VCAM-1/CD106 and negatively associated with levels of Flt-3 ligand. These findings indicate that prolonged MDPV intake causes changes in PFC cytokine levels that persist into abstinence; however, the functional ramifications of these changes remain to be fully elucidated. PubDate: 2023-11-10T00:00:00Z
Authors:Luciana Fernandes, Ralf Kleene, Ludovica Congiu, Sandra Freitag, Matthias Kneussel, Gabriele Loers, Melitta Schachner Abstract: IntroductionThe dopaminergic system plays a key role in the appropriate functioning of the central nervous system, where it is essential for emotional balance, arousal, reward, and motor control. The cell adhesion molecule close homolog of L1 (CHL1) contributes to dopaminergic system development, and CHL1 and the dopamine receptor D2 (D2R) are associated with mental disorders like schizophrenia, addiction, autism spectrum disorder and depression.MethodsHere, we investigated how the interplay between CHL1 and D2R affects the behavior of young adult male and female wild-type (CHL+/+) and CHL1-deficient (CHL1−/−) mice, when D2R agonist quinpirole and antagonist sulpiride are applied.ResultsLow doses of quinpirole (0.02 mg/kg body weight) induced hypolocomotion of CHL1+/+ and CHL1−/− males and females, but led to a delayed response in CHL1−/− mice. Sulpiride (1 mg/kg body weight) affected locomotion of CHL1−/− females and social interaction of CHL1+/+ females as well as social interactions of CHL1−/− and CHL1+/+ males. Quinpirole increased novelty-seeking behavior of CHL1−/− males compared to CHL1+/+ males. Vehicle-treated CHL1−/− males and females showed enhanced working memory and reduced stress-related behavior.DiscussionWe propose that CHL1 regulates D2R-dependent functions in vivo. Deficiency of CHL1 leads to abnormal locomotor activity and emotionality, and to sex-dependent behavioral differences. PubDate: 2023-11-09T00:00:00Z
Authors:Szabolcs Sáringer, Ágnes Fehér, Gyula Sáry, Péter Kaposvári Abstract: Statistical learning is assumed to be a fundamentally general sensory process across modalities, age, other cognitive functions, and even species. Despite this general role, behavioral testing on regularity acquisition shows great variance among individuals. The current study aimed to find neural correlates of visual statistical learning showing a correlation with behavioral results. Based on a pilot study, we conducted an EEG study where participants were exposed to associated stimulus pairs; the acquisition was tested through a familiarity test. We identified an oscillation in the gamma range (40–70 Hz, 0.5–0.75 s post-stimulus), which showed a positive correlation with the behavioral results. This change in activity was located in a left frontoparietal cluster. Based on its latency and location, this difference was identified as a late gamma activity, a correlate of model-based learning. Such learning is a summary of several top-down mechanisms that modulate the recollection of statistical relationships such as the capacity of working memory or attention. These results suggest that, during acquisition, individual behavioral variance is influenced by dominant learning processes which affect the recall of previously gained information. PubDate: 2023-11-08T00:00:00Z
Authors:Baitao Zeng, Haoyi Zhang, Qing Lu, Qingzi Fu, Yang Yan, Wan Lu, Pengpeng Ma, Chuanxin Feng, Jiawei Qin, Laipeng Luo, Bicheng Yang, Yongyi Zou, Yanqiu Liu Abstract: BackgroundEpilepsy is characterized by recurrent unprovoked seizures. Mutations in the voltage-gated sodium channel alpha subunit 1 (SCN1A) gene are the main monogenic cause of epilepsy. Type and location of variants make a huge difference in the severity of SCN1A disorder, ranging from the mild phenotype (genetic epilepsy with febrile seizures plus, GEFS+) to the severe phenotype (developmental and epileptic encephalopathies, DEEs). Dravet Syndrome (DS) is an infantile-onset DEE, characterized by drug-resistant epilepsy and temperature sensitivity or febrile seizures. Genetic test results reveal SCN1A variants are positive in 80% DS patients and DS is mainly caused by de novo variants.MethodsTrio-whole exome sequencing (WES) was used to detect variants which were associated with clinical phenotype of five probands with epilepsy or twitching. Then, Sanger sequencing was performed to validate the five novel SCN1A variants and segregation analysis. After analyzing the location of five SCN1A variants, the pathogenic potential was assessed.ResultsIn this study, we identified five novel SCN1A variants (c.4224G > C, c.3744_3752del, c.209del, c.5727_5734delTTTAAAACinsCTTAAAAAG and c.5776delT) as the causative variants. In the five novel SCN1A variants, four were de novo and the remaining one was inherited. All novel variants would be classified as “pathogenic” or “likely pathogenic.”ConclusionThe five novel SCN1A variants will enrich the SCN1A mutations database and provide the corresponding reference data for the further genetic counseling. PubDate: 2023-11-08T00:00:00Z
Authors:Esther R.-H. Lin, Alyssa R. Roeckner, Negar Fani, Natalie Merrill, Charles F. Gillespie, Timothy D. Ely, Bekh Bradley, Vasiliki Michopoulos, Abigail Powers, Tanja Jovanovic, Jennifer S. Stevens Abstract: IntroductionExposure to traumatic events and stressful life experiences are associated with a wide range of adverse mental and physical health outcomes. Studies have found post-traumatic stress disorder (PTSD), depression, and anxiety sensitivity occurrence to be common in addition to inflammatory diseases like asthma, especially in women. Moreover, overlapping neurobiological mechanisms have been linked to both PTSD and asthma.MethodsIn the current study, n = 508 women reported on presence of lifetime asthma diagnosis and symptoms of trauma-related psychopathology including PTSD and depression. A separate group of female participants (n = 64) reported on asthma, PTSD, depression and anxiety sensitivity, and underwent functional MRI scans during a fearful faces task, and their anterior insula responses were analyzed.ResultsOverall, PTSD and depression severity were significantly higher in those with asthma versus those without asthma. There was a positive association between anterior insula response to social threat cues and depression symptoms only among individuals without a lifetime presence of asthma.DiscussionThese findings provide continued evidence on the interactions between stress, neural mechanisms involved in interoception and salience detection, and trauma-related psychopathology. PubDate: 2023-10-31T00:00:00Z
Authors:Leah M. Truckenbrod, Emily M. Cooper, Alexa-Rae Wheeler, Caitlin A. Orsini Abstract: Navigating complex decisions and considering their relative risks and rewards is an important cognitive ability necessary for survival. However, use of and dependence on illicit drugs can result in long-lasting changes to this risk/reward calculus in individuals with substance use disorder. Recent work has shown that chronic exposure to cocaine causes long-lasting increases in risk taking in male and female rats, but there are still significant gaps in our understanding of the relationship between cocaine use and changes in risk taking. For example, it is unclear whether the magnitude of cocaine intake dictates the extent to which risk taking is altered. To address this, male and female Sprague–Dawley rats underwent cocaine (or sucrose) self-administration and, following a period of abstinence, were trained and tested in a rodent model of risky decision making. In this behavioral task, rats made discrete-trial choices between a lever associated with a small food reward (i.e., “safe” option) and a lever associated with a larger food reward accompanied by a variable risk of footshock delivery (i.e., “risky” option). Surprisingly, and in contrast to prior work in Long-Evans rats, there were no effects of cocaine self-administration on choice of the large, risky reward (i.e., risk taking) during abstinence in males or females. There was, however, a significant relationship between cocaine intake and risk taking in female rats, with greater intake associated with greater preference for the large, risky reward. Relative to their sucrose counterparts, female rats in the cocaine group also exhibited irregular estrous cycles, characterized by prolonged estrus and/or diestrus phases. Collectively, these data suggest that there may be strain differences in the effects of cocaine on risk taking and highlight the impact that chronic cocaine exposure has on hormonal cyclicity in females. Future work will focus on understanding the neural mechanisms underlying cocaine’s intake-dependent effects on risk taking in females, and whether this is directly related to cocaine-induced alterations in neuroendocrine function. PubDate: 2023-10-27T00:00:00Z
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