Behavioral and Brain Functions最新文献

Background: Animals exhibit a wide range of social behaviors, including positive actions that promote social cohesion and negative behaviors associated with asserting dominance. While these behaviors are often viewed as opposites, they can also exist independently or coexist in complex ways, necessitating further investigation into their interrelationships.

Results: To study the interplay between these two types of behaviors, we examined mouse social behaviors using resident-intruder assays and revealed a negative correlation between social aggression and prosocial allogrooming. Suppressing aggressive motivation through various manipulations, including social subordination, olfaction ablation, and inhibition of aggressive neural circuits, led to an increased display of allogrooming behavior. The mouse findings prompted us to further explore the relationship between aggression and prosocial behaviors in preschool children. Similarly, we observed a negative association between aggression and prosocial behaviors, which were potentially influenced by their inhibitory control abilities.

Conclusions: Through this cross-species study, we uncovered the inhibitory impact of aggressive neural circuits on mouse allogrooming and established a link between aggression and prosocial behaviors in children. These insights offer valuable implications for understanding and potentially influencing social interactions in both animal and human contexts, with potential applications in preschool education practices.

Background: Mood disorders, particularly depression and anxiety, are associated with zinc dyshomeostasis and aberrant GABAergic signaling. Activation of ZnR/GPR39 by synaptic zinc in the hippocampus triggers phosphorylation of extracellular regulated kinase (ERK1/2), which regulates the K⁺/Cl^- cotransporter (KCC2) and thereby GABAergic inhibitory neurotransmission and seizure activity. Therefore, we studied whether impaired ZnR/GPR39 signaling is linked to anxiety-related behavior in male or female mice.

Results: Using the acoustic startle response, elevated plus maze, and open field test, we found increased anxiety-related behavior in ZnR/GPR39 knockout (KO) mice. Despite a well-established sex difference, where females are typically more prone to anxiety, both male and female ZnR/GPR39 KO mice exhibited increased anxiety-related behavior compared to wildtype (WT) mice. Additionally, ZnR/GPR39 KO mice displayed impaired motor coordination in the pole and rotarod tests but did not show reduced muscle strength, as indicated by a grip test. Finally, we found intrinsic alterations in the expression level of KCC2, a major Cl^- transporter regulating GABAergic signaling, in the amygdala of naïve ZnR/GPR39 KO mice compared to controls.

Conclusions: Our findings indicate that loss of ZnR/GPR39 enhances anxiety-related behavior in both male and female mice. Moreover, ZnR/GPR39 KO mice exhibit impaired motor coordination, which may be associated with increased anxiety. Finally, we demonstrate that loss of ZnR/GPR39 modulates the expression of KCC2 in the amygdala. Thus, we propose that ZnR/GPR39 can serve as a target for regulating GABAergic signaling in anxiety treatment.

Neural entrainment has become a popular technique to non-invasively manipulate brain rhythms via external, periodic stimulation. However, there is still debate regarding its underlying mechanisms and effects on brain activity. Here, we used EEG recordings during a visual entrainment paradigm to assess characteristic changes in the spectral content of EEG signals due to entrainment. Our results demonstrate that entrainment not only increases synchrony between neural oscillations and the entraining stimulus but also elicits previously unreported spectral tuning effects and long-lasting after-effects. These findings offer compelling evidence for the presence of dedicated, flexible, and adaptive mechanisms for neural entrainment, which may have key roles in adjusting the sensitivity and dynamic range of brain oscillators in response to environmental temporal structures.

Background: Cutibacterium acnes(C. acnes), a Gram-positive anaerobe and a dominant bacterium species in the sebaceous follicles of the face was detected in the brain of Alzheimer's disease (AD) patients. It has been found that C. acnes activates non-specifically the innate immune system by producing proinflammatory cytokines and can participate in brain inflammation. We hypothesise that C. acnes could influence the brain through the structural alteration in axons and dendrites of neurons.

Methods: In this regard, the hippocampus of rats was infected with C. acnes, and memory retention, amyloid-β (Aβ_1-42) deposition, hyperphosphorylated tau protein (p-Tau) formation, and expression levels of MAP2 and β-tubulin proteins in the hippocampus tissues were investigated.

Results: C. acnes-infected rats displayed memory deficits and Aβ_1-42 deposits were detected in their hippocampus tissue up to 7 days post-infection. C. acnes was neurotoxic and exerted detrimental effects on MAP2 and β-tubulin proteins, which are required for normal neuronal function. An elevated level of p-Tau was also identified in infected animals.

Conclusion: Based on these results, we propose that C. acnes infection of the brain participates in the initiation of the pathogenesis of sporadic AD through degeneration of axons and dendrites.

Background: The cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ has afforded neuroprotection in experimental models of Parkinson's disease (PD) based on mitochondrial dysfunction (6-hydroxydopamine-lesioned mice) and neuroinflammation (LPS-lesioned mice). Now, we aim to explore VCE-003.2 neuroprotective properties in a PD model that also involves protein dysregulation, other key event in PD pathogenesis.

Methods: To this end, an adeno-associated viral vector serotype 9 coding for a mutated form of the α-synuclein gene (AAV9-SynA53T) was unilaterally delivered in the substantia nigra pars compacta (SNpc) of mice. This model leads to motor impairment and progressive loss of tyrosine hydroxylase-labelled neurons in the SNpc.

Results: Oral administration of VCE-003.2 at 20 mg/kg for 14 days improved the performance of mice injected with AAV9-SynA53T in various motor tests, correlating with the preservation of tyrosine hydroxylase-labelled neurons in the SNpc. VCE-003.2 also reduced reactive microgliosis and astrogliosis in the SNpc. Furthermore, we conducted a transcriptomic analysis in the striatum of mice injected with AAV9-SynA53T and treated with either VCE-003.2 or vehicle, as well as control animals. This analysis aimed to identify gene families specifically altered by the pathology and/or VCE-003.2 treatment. Our data revealed pathology-induced changes in genes related to mitochondrial function, lysosomal cell pathways, immune responses, and lipid metabolism. In contrast, VCE-003.2 treatment predominantly affected the immune response through interferon signaling.

Conclusion: Our study broadens the neuroprotective potential of VCE-003.2, previously described against mitochondrial dysfunction, oxidative stress, glial reactivity and neuroinflammation in PD. We now demonstrate its efficacy against another key pathogenic event in PD as α-synuclein dysregulation. Furthermore, our investigation sheds light on the molecular mechanisms underlying VCE-003.2 revealing its role in regulating interferon signaling. These findings, together with a favorable ADMET profile, enhance the preclinical interest of VCE-003.2 towards its future clinical development in PD.

Background: Nicotine dependence is associated with glutamatergic neurotransmission in the caudate and putamen (CPu) of the forebrain which includes alterations in the structure of dendritic spines at glutamate synapses. These changes after nicotine exposure can lead to the development of habitual behaviors such as smoking. The present study investigated the hypothesis that cofilin, an actin-binding protein that is linked to the GluN2B subunits of N-methyl-D-aspartate (NMDA) receptors regulates the morphology of dendritic spines in the neurons of the CPu after repeated exposure to nicotine.

Results: Adult male rats received subcutaneous injections of nicotine (0.3 mg/kg/day) or vehicle for seven consecutive days. DiI staining was conducted to observe changes in dendritic spine morphology. Repeated subcutaneous injections of nicotine decreased the phosphorylation of cofilin while increasing the formation of thin spines and filopodia in the dendrites of medium spiny neurons (MSN) in the CPu of rats. Bilateral intra-CPu infusion of the cofilin inhibitor, cytochalasin D (12.5 µg/µL/side), restored the thin spines and filopodia from mushroom types after repeated exposure to nicotine. Similar results were obtained from the bilateral intra-CPu infusion of the selective GluN2B subunit antagonist, Ro 25-6981 (4 µM/µL/side). Bilateral intra-CPu infusion of cytochalasin D that interferes with the actin-cofilin interaction attenuated the repeated nicotine-induced increase in locomotor sensitization in rats.

Conclusions: These findings suggest that active cofilin alters the structure of spine heads from mushroom to thin spine/filopodia by potentiating actin turnover, contributing to behavioral sensitization after nicotine exposure.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is significantly increasing, resulting in severe distress. The approved treatment for ASD only partially improves the sympoms, but it does not entirely reverse the symptoms. Developing novel disease-modifying drugs is essential for the continuous improvement of ASD. Because of its pleiotropic effect, atorvastatin has been garnered attention for treating neuronal degeneration. The present study aimed to investigate the therapeutic effects of atorvastatin in autism and compare it with an approved autism drug (risperidone) through the impact of these drugs on TLR4/NF-κB/NOX-2 and the apoptotic pathway in a valproic acid (VPA) induced rat model of autism.

Methods: On gestational day 12.5, pregnant rats received a single IP injection of VPA (500 mg/kg), for VPA induced autism, risperidone and atorvastatin groups, or saline for control normal group. At postnatal day 21, male offsprings were randomly divided into four groups (n = 6): control, VPA induced autism, risperidone, and atorvastatin. Risperidone and atorvastatin were administered from postnatal day 21 to day 51. The study evaluated autism-like behaviors using the three-chamber test, the dark light test, and the open field test at the end of the study. Biochemical analysis of TLR4, NF-κB, NOX-2, and ROS using ELISA, RT-PCR, WB, histological examination with hematoxylin and eosin and immunohistochemical study of CAS-3 were performed.

Results: Male offspring of prenatal VPA-exposed female rats exhibited significant autism-like behaviors and elevated TLR4, NF-κB, NOX-2, ROS, and caspase-3 expression. Histological analysis revealed structural alterations. Both risperidone and atorvastatin effectively mitigated the behavioral, biochemical, and structural changes associated with VPA-induced rat model of autism. Notably, atorvastatin group showed a more significant improvement than risperidone group.

Conclusions: The research results unequivocally demonstrated that atorvastatin can modulate VPA-induced autism by suppressing inflammation, oxidative stress, and apoptosis through TLR4/NF-κB/NOX-2 signaling pathway. Atorvastatin could be a potential treatment for ASD.

Background: Recent research has indicated that parental use of central nervous system-targeting medications during periconceptional periods may affect offspring across various developmental and behavioral domains. The present study sought to investigate the potential influence of paternal use of donepezil, a specific reversible central acetylcholinesterase inhibitor that activates the cholinergic system to promote cognition, on offspring.

Results: In this study, male rats were bred after 21 days of oral donepezil administration at a dose of 4 mg/kg to generate F1 offspring. Both male and female F₁ offspring displayed enhanced performance in learning and short-term memory tests, including novel object recognition, Y maze, and operant learning. Transcriptomic analysis revealed notable alterations in genes associated with the extracellular matrix in the hippocampal tissue of the F1 generation. Integration with genes related to intelligence identified potential core genes that may be involved in the observed behavioral enhancements.

Conclusions: These findings indicate that prolonged paternal exposure to donepezil may enhance the learning and memory abilities of offspring, possibly by targeting nonneural, extracellular regions. Further research is required to fully elucidate any potential transgenerational effects.

Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with heterogeneous symptomatology. Arguably, the most pervasive shortfall of ASD are the deficits in sociability and the animal models of the disorder are expected to exhibit such impairments. The most widely utilized behavioral task for assessing sociability in rodents is the Three-Chamber Social Interaction Test (SIT). However, SIT has been yielding inconsistent results in social interaction behavior across different rodent models of ASD, which could be pointing to the suboptimal methodology of the task. Here, we compared social behavior assessed in SIT and in another prominent sociability behavioral assay, Reciprocal Interaction Test (RCI), in a SH3 and multiple ankyrin repeated domains 3 (SHANK3) mouse model of ASD. Head-to-head comparison showed no association (p = 0.15, 0.25, 0.43) and a fixed bias (p = 0.01, < 0.001, < 0.001) in sociability assessment between the behavioral assays in both wild-type (WT) controls and Shank3B^(-/-) mice. Adult Shank3B^(-/-) mice of both sexes displayed normative sociability in SIT when compared to the WT controls (p = 0.74) but exhibited less than half of social interaction (p < 0.001) and almost three times more social disinterest (p < 0.001) when compared to WT mice in RCI. At least in the Shank3B^(-/-) mouse model of ASD, we presume RCI could be a preferable way of assessing social interaction compared to SIT. Considering the variability of animal models of ASD and the wide palette of tools available for the assessment of their behavior, a consensus approach would be needed for observational and interventional analyses.

Correction to: Behavioral and Brain Functions (2024) 20:11

https://doi.org/10.1186/s12993-024-00236-z

Following publication of the original article [1], the author noticed an error in Results section. The correlation results for the influence of age on various variables were incorrectly provided. This error has occurred during the transcription of result which has been corrected with this correction.

In Results section under the heading “Behavioral results”, the sentence should read, “The findings indicated that age was not significantly correlated with any variables (r_FSC=.087, p = .360; r_PA=-.117, p = .215; r_PE=-.123, p = .193; r_PO=.078, p = .409; r_NE=.132, p = .162; r_NO=.153, p = .105)” instead of “The findings indicated that age was not significantly correlated with any variables (r_FSC=0.051, p = 0.590; r_PA=0.017, p = 0.856; r_PE = − 0.017, p = 0.854; r_PO =0.036, p = 0.700; r_NE =0.034, p = 0.718; r_NO=0.039, p = 0.682)”.

1. Zhao X, Zhang R, Feng T. The vmPFC-IPL functional connectivity as the neural basis of future self-continuity impacted procrastination: the mediating role of anticipated positive outcomes. Behav Brain Funct. 2024;20:11. https://doi.org/10.1186/s12993-024-00236-z.

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Authors and Affiliations

1. Faculty of Psychology, Southwest University, No. 2, Tian Sheng RD., Beibei, Chongqing, 400715, China

   Xiaotian Zhao, Rong Zhang & Tingyong Feng

2. Key Laboratory of Cognition and Personality, Ministry of Education, Chongqing, China

   Tingyong Feng

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