Neuroscience
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Neuroligins are a family of cell adhesion molecules critical in establishing proper central nervous system connectivity; disruption of neuroligin signaling in vivo precipitates a broad range of cognitive deficits. Despite considerable recent progress, the specific synaptic function of neuroligin-1 (NL1) remains unclear. A current model proposes that NL1 acts exclusively to mature pre-existent synaptic connections in an activity-dependent manner. ⋯ Consistent with these findings, we observed profoundly greater recruitment of synapsin-positive presynaptic terminals by NL1 than SC1 in a mixed-culture assay of artificial synaptogenesis between primary neurons and heterologous cells. Collectively, our results contend multiple aspects of the proposed model of NL1 and SC1 function and motivate an alternative model whereby SC1 may mature synaptic connections forged by NL1. Supporting this model, we present evidence that combined NL1 and SC1 overexpression triggers excitotoxic neurodegeneration through SC1 signaling at synaptic connections initiated by NL1.
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Maternal separation (MS) has been used to model the causal relationship between early life stress and the later stress-over-reactivity and affective disorders. Arginine vasopressin (AVP) is among several factors reported to be abnormal. The role of AVP on anxiety is still unclear. ⋯ Volumes of AVP-PVN and AVP-SON measured at PND75 had marked increases as well as AVP plasma concentration at 12h of water deprivation (WD). MS rats demonstrated a high conditioned anxious state under VCT paradigm whereas no difference was found under EPM. These data demonstrate direct relationships between enhanced AVP neuronal activation and a potentiated vasopressin system, and this latter one with high conditioned anxiety in MS male rats.
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The glomeruli are the first synaptic relay on the olfactory pathway and play a basic role in smell perception. Glomerular degeneration occurs in humans with age and in Alzheimer's disease (AD). The glomeruli heavily express β-amyloid precursor protein (APP), β-secretase (BACE1) and γ-secretase complex. ⋯ Reduced glomerular area was detected in 6-12-month-old 5XFAD mice relative to non-transgenic controls, and in aged humans relative to young/adult controls, more robust in AD than aged subjects without cerebral amyloid and tau pathologies. The results suggest that olfactory nerve terminals may undergo age-related dystrophic and degenerative changes in AD model mice and humans, which are associated with increased labeling for amyloidogenic proteins but not local extracellular Aβ deposition. The identified axon terminal pathology might affect neuronal signal transmission and integration at the first olfactory synaptic relay.
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Impulsive people have a strong urge to act without thinking. It is sometimes regarded as a positive trait but rash impulsiveness is also widely present in clinical disorders such as attention deficit hyperactivity disorder (ADHD), drug dependence, mania, and antisocial behaviour. ⋯ With this progress has come the understanding that impulsivity is a multi-faceted behavioural trait involving neurally and psychologically diverse elements. We discuss the significance of this heterogeneity for clinical disorders expressing impulsive behaviour and the pivotal contribution made by the brain dopamine and serotonin systems in the aetiology and treatment of behavioural syndromes expressing impulsive symptoms.
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The effects of regular exercise versus a single bout of exercise on cognition, anxiety, and mood were systematically examined in healthy, sedentary young adults who were genotyped to determine brain-derived neurotrophic factor (BDNF) allelic status (i.e., Val-Val or Val66Met polymorphism). Participants were evaluated on novel object recognition (NOR) memory and a battery of mental health surveys before and after engaging in either (a) a 4-week exercise program, with exercise on the final test day, (b) a 4-week exercise program, without exercise on the final test day, (c) a single bout of exercise on the final test day, or (d) remaining sedentary between test days. Exercise enhanced object recognition memory and produced a beneficial decrease in perceived stress, but only in participants who exercised for 4 weeks including the final day of testing. ⋯ Importantly, exercise-induced changes in cognition were not correlated with changes in mood/anxiety, suggesting that separate neural systems mediate these effects. These data in humans mirror recent data from our group in rodents. Taken together, these current findings provide new insights into the behavioral and neural mechanisms that mediate the effects of physical exercise on memory and mental health in humans.