Behavioural Brain Research最新文献

Central cholinergic system and endocannabinoid, anandamide exhibits anti-compulsive-like behavior in mice. However, the role of the central cholinergic system in the anandamide-induced anti-compulsive-like behavior is still unexplored. Therefore, the present study assessed the role of central cholinergic transmission in the anandamide-induced anti-compulsive activity using a marble-burying behavior (MBB) model in mice. The modulation in the anandamide-induced effect on MBB was evaluated using mice with altered central cholinergic transmission achieved by pretreatment (i.c.v.) with various cholinergic agents like acetylcholine (ACh), acetylcholinesterase inhibitor (AChEI), neostigmine, nicotine, mAChR antagonist, atropine, and nAChR antagonist, mecamylamine. The influence of anandamide treatment on the brain AChE activity was also evaluated. The results revealed that i.c.v. injection of anandamide (10, 20 µg/mouse, i.c.v.) dose-dependently reduced MBB in mice. Moreover, anandamide in all the tested doses inhibited the brain AChE activity indicating the role of an enhanced central cholinergic transmission in its anti-compulsive-like effect . Furthermore, the anti-compulsive-like effect of anandamide (20 µg/mouse, i.c.v.) was found to be enhanced in mice centrally pre-treated with, ACh (0.1 µg/mouse, i.c.v.) or AChEI, neostigmine (0.3 µg/mouse, i.c.v.). In addition, the anandamide-induced anti-compulsive-like effect was significantly increased in mice pre-treated with a low dose of nicotine (0.1 µg/mouse, i.c.v.) while, it was attenuated by the higher dose of nicotine (2 µg/mouse, i.c.v.). On the other hand, the anandamide (20 µg/mouse, i.c.v.) induced anti-compulsive-like effect was found to be diminished in mice pre-treated with mAChR antagonist, atropine (0.1, 0.5 µg/mouse, i.c.v.) and pre-injection of nAChR antagonist, mecamylamine (0.1, 0.5 µg/mouse, i.c.v.) potentiated the anandamide induced anti-compulsive-like response in mice. Thus, the present investigation delineates the modulatory role of an enhanced central cholinergic transmission in the anandamide-induced anti-compulsive-like behavior in mice by inhibition of brain AChE or via muscarinic and nicotinic receptors mediated mechanism.

Glutamatergic alteration is one of the potential mechanisms of depression. However, there is no consensus on whether glutamate metabolism changes affect the myelin structure of depression in mouse models. Glutamate chemical exchange saturation transfer (GluCEST) is a novel and powerful molecular imaging technique that can visualize glutamate distribution. In this study, we used the GluCEST imaging technique to look at glutamate levels in mice under chronic unpredictable mild stress (CUMS) and how they relate to demyelination. The CUMS mice were exposed to different stress factors for 6 weeks. Evaluated of depression in CUMS mice by behavioral tests. MRI scans were then performed, including T2-mapping, GluCEST, and diffusion tensor imaging (DTI) sequences. Brain tissues were collected for Luxol Fast Blue staining and immunofluorescence staining to analyze the changes in the myelin sheath. Artificially sketched regions of interest (ROI) (corpus callosum, hippocampus, and thalamus) were used to calculate the GluCEST value, fractional anisotropy (FA), and T2 value. Compared with the control group, the GluCEST value in the ROIs of CUMS mice significantly decreased. Similarly, the FA value in ROIs was lower in the CUMS group than in the CTRL group, but the T2 value did not differ significantly between the two groups. The histological results showed that ROIs in the CUMS group had demyelination compared with the CTRL group, indicating that DTI was more sensitive than T2 mapping in detecting myelin abnormalities. Furthermore, the GluCEST value in the ROIs correlates positively with the FA value. These findings suggest that altered glutamate metabolism may be one of the important factors leading to demyelination in depression, and GluCEST is expected to serve as an imaging biological marker for the diagnosis of demyelination in depression.

Schizophrenia is a disorder with a higher cognitive decline in early adulthood, causing impaired retention of episodic memories. However, the physiological and behavioral functions that underlie cognitive deficits with a potential mechanism to ameliorate and improve cognitive performance are unknown. In this study, we used the MK-801 neurodevelopmental schizophrenia-like model. Rats were divided into two groups: one received MK-801, and the other received saline for five consecutive days (7–11 postnatal days, PND). We evaluated synaptic plasticity late-LTP and spatial memory consolidation in early adolescence and young adulthood using extracellular field recordings in acute hippocampal slices and the Barnes maze task. Next, we examined D1 receptor (D1R) activation as a mechanism to ameliorate cognitive impairments. Our results suggest that MK-801 neonatal treatment induces impairment in late-LTP expression and deficits in spatial memory retrieval in early adolescence that is maintained until young adulthood. Furthermore, we found that activation of dopamine D1R ameliorates the impairments and promotes a robust expression of late-LTP and an improved performance in the Barnes maze task, suggesting a novel and potential therapeutic role in treating cognitive impairments in schizophrenia.

Background

Maternal separation (MS) in rodents is a paradigm of early life events that affects neurological development in depression. Adolescence is a time of dramatic increases in psychological vulnerability, and being female is a depression risk factor. However, data on whether different MS scenarios affect behavioral deficits and the potential mechanisms in adolescent female mice are limited.

Methods

C57BL/6 J female pups were exposed to different MS (no MS, NMS; MS for 15 min/day, MS15; or 180 min/day, MS180) from postnatal day (PND)1 to PND21 and subjected for behavioral tests during adolescence. Behavioural tests, specifically the open field test (OFT), novel object recognition test (NOR) test and tail suspension test (TST), were performed. The expression of proinflammatory cytokines, hippocampal neurogenesis, neuroinflammation, and gut microbiota were also assessed.

Results

The results showed that MS180 induced emotional behavioral deficits and object recognition memory impairment; however, MS15 promoted object recognition memory in adolescent females. MS180 decreased hippocampal neurogenesis of adolescent females, induced an increase in microgliosis, and increased certain inflammatory factors in the hippocampus, including TNF-α, IL-1β, and IL-6. Furthermore, different MS altered gut microbiota diversity, and alpha diversity in the Shannon index was negatively correlated with the peripheral inflammatory factors TNF-α, IL-1β, and IL-6. Species difference analysis showed that the gut microbiota composition of the phyla Desulfobacterota and Proteobacteria was affected by the MS.

Limitations

The sex differences in adolescent animal and causality of hippocampal neurogenesis and gut microbiota under different MS need to be further analyzed in depression.

Conclusion

This study indicates different MS affect recognition memory and emotional behaviors in adolescent females, and gut microbiota-neuroinflammation and hippocampal neurogenesis may be a potential site of early neurodevelopmental impairment in depression.

This study investigated the risk to social behavior and cognitive flexibility induced by chronic social defeat stress (CSDS) during early and late adolescence (EA and LA). Utilizing the “resident-intruder” stress paradigm, adolescent male Sprague-Dawley rats were exposed to CSDS during either EA (postnatal days 29–38) or LA (postnatal days 39–48) to explore how social defeat at different stages of adolescence affects behavioral and cognitive symptoms commonly associated with psychiatric disorders. After stress exposure, the rats were assessed for anxiety-like behavior in the elevated plus maze, social interaction, and cognitive flexibility through set-shifting and reversal-learning tasks under immediate and delayed reward conditions. The results showed that CSDS during EA, but not LA, led to impaired cognitive flexibility in adulthood, as evidenced by increased perseverative and regressive errors in the set-shifting and reversal-learning tasks, particularly under the delayed reward condition. This suggests that the timing of stress exposure during development has a significant impact on the long-term consequences for behavioral and cognitive function. The findings highlight the vulnerability of the prefrontal cortex, which undergoes critical maturation during early adolescence, to the effects of social stress. Overall, this study demonstrates that the timing of social stressors during adolescence can differentially shape the developmental trajectory of cognitive flexibility, with important implications for understanding the link between childhood/adolescent adversity and the emergence of psychiatric disorders.

Despite earlier research demonstrating the immunomodulatory effects of acute and chronic exercise in many medical illnesses, there is a lack of literature evaluating the acute and chronic effects of exercise on the cytokine levels in individuals with bipolar disorder (BD) or schizophrenia (SCH). This study aims to examine the acute effects of resistance exercise on cytokines and the chronic effects of resistance exercise by 10 weeks on cytokine levels, symptoms of disease, and muscular strength in individuals with BD and SCH. The included individuals (N=10) performed a single session of band-elastic resistance exercises (six exercises, 3 sets of 12–15 repetitions, 60 seconds of interval between sets). A sub-sample (N=6) of individuals performed a supervised band-elastic resistance exercise program (2 times a week, for 10 weeks, 6 exercises, 3 sets of 12–15 repetitions, 60 seconds of interval). We verified for acute effects: IL-2 (P=0.0085) and IL-4 (P=0.0253) levels increased, while IL-6 decreased (P=0.0435), and for chronic effects: increased IL-2 and IL-4 levels (significant effect size - Pre vs Post), a decrease in disease symptoms, and an increase in muscular strength. This study adds to what is already known about how resistance exercises affect people with BD and SCH in both short-term (systemic cytokines levels) and long-term (symptoms of disease, muscular strength, and systemic cytokines levels).

Post-traumatic stress disorder (PTSD) is a mental disorder resulting from traumatic events which are characterized primarily by anxiety and depressive disorder. In this study, we determine the role of gut bacteria in PTSD. PTSD-like symptoms were produced by single prolonged stress (SPS). SPS animals showed increased levels of anxiety as measured by the elevated plus maze test, while depressive behaviour was confirmed using sucrose preference, force swim, and tail suspension tests. Gut dysbiosis was confirmed in PTSD animals by next-generation sequencing of 16 s RNA of faecal samples, while these animals also showed increased intestinal permeability and altered intestinal ultrastructure. Probiotic treatment increases beneficial microbiota, improves intestinal health and reduces PTSD-associated anxiety and depression. We also found a decrease in cortical BDNF levels in PTSD animals, which was reversed after probiotic administration. Here, we establish the link between gut dysbiosis and PTSD and show that probiotic treatment may improve the outcome of PTSD like symptoms in mice.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative primarily affecting motor neurons, leading to disability and neuronal death, and ATP-Binding Cassette (ABC) transporter due to their role in drug efflux and modulation of various cellular pathways contributes to the pathogenesis of ALS. In this article, we extensively investigated various molecular and mechanistic pathways linking ALS transporter to the pathogenesis of ALS; this involves inflammatory pathways such as Mitogen-Activated Protein Kinase (MAPK), Phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/Akt), Toll-Like Receptor (TLR), Glycogen Synthase Kinase 3β (GSK-3β), Nuclear Factor Kappa-B (NF-κB), and Cyclooxygenase (COX). Oxidative pathways such as Astrocytes, Glutamate, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Sirtuin 1 (SIRT-1), Forkhead box protein O (FOXO), Extracellular signal-regulated kinase (ERK). Additionally, we delve into the role of autophagic pathways like TAR DNA-binding protein 43 (TDP-43), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and lastly, the apoptotic pathways. Furthermore, by understanding these intricate interactions, we aim to develop novel therapeutic strategies targeting ABC transporters, improving drug delivery, and ultimately offering a promising avenue for treating ALS.

Head trauma often impairs cognitive processes mediated within the prefrontal cortex (PFC), leading to impaired decision making and risk-taking behavior. Mild traumatic brain injury (mTBI) accounts for approximately 80 % of reported head injury cases. Most neurological symptoms of a single mTBI are transient; however, growing evidence suggests that repeated mTBI (rmTBI) results in more severe impairments that worsen with each subsequent injury. Although mTBI-induced disruption of risk/reward decision making has been characterized, the potential for rmTBI to exacerbate these effects and the neural mechanisms involved are unknown. Catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), modulate PFC-mediated functions. Imbalances in catecholamine function have been associated with TBI and may underlie aberrant decision making. We used a closed head-controlled cortical impact (CH-CCI) model in rats to evaluate the effects of rmTBI on performance of a probabilistic discounting task of risk/reward decision making behavior and expression levels of catecholamine regulatory proteins within the PFC. RmTBI produced transient increases in risky choice preference in both male and female rats, with these effects persisting longer in females. Additionally, rmTBI increased expression of the catecholamine synthetic enzyme, tyrosine hydroxylase (TH), within the orbitofrontal (OFC) region of the PFC in females only. These results suggest females are more susceptible to rmTBI-induced disruption of risk/reward decision making behavior and dysregulation of catecholamine synthesis within the OFC. Together, using the CH-CCI model of rodent rmTBI to evaluate the effects of multiple insults on risk-taking behavior and PFC catecholamine regulation begins to differentiate how mTBI occurrences affect neuropathological outcomes across different sexes.

Chronic social defeat stress (CSDS), a widely used rodent model of stress, reliably leads to decreased social interaction in stress susceptible animals. Here, we investigate a role for fear learning in this response using male 129 Sv/Ev mice, a strain that is more vulnerable to CSDS than the commonly used C57BL/6 strain. We first demonstrate that defeated 129 Sv/Ev mice avoid a CD-1 mouse, but not a conspecific, indicating that motivation to socialize is intact in this strain. CD-1 avoidance is characterized by approach behavior that results in running in the opposite direction, activity that is consistent with a threat response. We next test whether CD-1 avoidance is subject to the same behavioral changes found in traditional models of Pavlovian fear conditioning. We find that associative learning occurs across 10 days CSDS, with defeated mice learning to associate the color of the CD-1 coat with threat. This leads to the gradual acquisition of avoidance behavior, a conditioned response that can be extinguished with 7 days of repeated social interaction testing (5 tests/day). Pairing a CD-1 with a tone leads to second-order conditioning, resulting in avoidance of an enclosure without a social target. Finally, we show that social interaction with a conspecific is a highly variable response in defeated mice that may reflect individual differences in generalization of fear to other social targets. Our data indicate that fear conditioning to a social target is a key component of CSDS, implicating the involvement of fear circuits in social avoidance.