Neuroscience
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Prenatal stress (PNS) is a significant risk factor for the development of psychopathology in adulthood such as anxiety, depression, schizophrenia and addiction. Animal models of PNS resemble many of the effects of PNS on humans and provide a means to study the accumulated effects of PNS over several generations on brain function. Here, we examined how mild PNS delivered during the third week in utero over four consecutive generations affects behavioral flexibility and functional signaling among cortical and limbic structures. ⋯ The coherence of FPs between brain regions, however, was much higher in MGPNS animals among all structures and for most frequency bands. We propose that this pattern of changes in brain signaling reflects a simplification of network processing, which is consistent with reports of reduced spine density and dendritic complexity in the brains of animals receiving PNS. Our data support the proposal that recurrent ancestral stress leads to adaptations in the brain, and that these may confer adaptive behavior in some circumstances as compared to single-generation PNS.
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The development and exacerbation of depression and anxiety are associated with exposure to repeated psychosocial stress. Stress is known to affect the bidirectional communication between the nervous and immune systems leading to elevated levels of stress mediators including glucocorticoids (GCs) and catecholamines and increased trafficking of proinflammatory immune cells. Animal models, like the repeated social defeat (RSD) paradigm, were developed to explore this connection between stress and affective disorders. ⋯ Recently, the observation that these monocytes have the ability to traffic to the brain perivascular spaces and parenchyma have provided mechanisms by which these peripheral cells may contribute to the prolonged anxiety-like behavior associated with RSD. The data that have been amassed from the RSD paradigm and others recapitulate many of the behavioral and immunological phenotypes associated with human anxiety disorders and may serve to elucidate potential avenues of treatment for these disorders. Here, we will discuss novel and key data that will present an overview of the neuroendocrine, immunological and behavioral responses to social stressors.
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Polypeptides produced in the gastrointestinal tract, stomach, adipocytes, pancreas and brain that influence food intake are referred to as 'feeding-related' peptides. Most peptides that influence feeding exert an inhibitory effect (anorexigenic peptides). In contrast, only a few exert a stimulating effect (orexigenic peptides), such as ghrelin. ⋯ VTA dopamine neurons encode cues that predict rewards and phasic release of dopamine in the ventral striatum motivates animals to forage for food. To elucidate how feeding-related peptides regulate reward pathways is of importance to reveal the mechanisms underlying non-homeostatic or hedonic feeding. Here, we review the current knowledge of how anorexigenic peptides and orexigenic peptides act within the VTA.
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Fetal striatal transplantation has emerged as a new therapeutic strategy in Huntington's disease (HD). Hypoxia is one of the microenvironmental stress conditions to which fetal tissue is exposed as soon as it is isolated and transplanted into the diseased host brain. Mechanisms that support neuroblast survival and replenishment of damaged cells within the HD brain in the hypoxic condition have yet to be fully elucidated. ⋯ In particular, ET-1 stimulated HSP cell survival through ETA in normoxic conditions and through ETB during hypoxia. Accordingly, ETA expression was down-regulated, while ETB expression was up-regulated by CoCl2 treatment. Overall, our results support the idea that HSP cells possess the machinery for their adaptation to hypoxic conditions and that neurotrophic factors, such as FGF2 and ET-1, may sustain neurogenesis and long-term survival through complex receptor-mediated mechanisms.
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Orbitofrontal reality filtering (ORF) denotes a little known but vital memory control mechanism, expressed at 200-300ms after stimulus presentation, that allows one to sense whether evoked memories (thoughts) refer to present reality and can be acted upon, or not. Its failure induces reality confusion evident in confabulations that patients act upon and disorientation. In what way ORF differs from temporal order judgment (TOJ), that is, the conscious knowledge about when something happened in the past, has never been explored. ⋯ We conclude that the task of consciously ordering memories in the immediate past (TOJ) is effortful and slow in contrast to sensing memories' relation with the present (ORF). Both functions invoke similar early electrocortical processes which then rapidly dissociate and engage different brain areas. The results are consistent with the different consequences of the two mechanisms' dysfunction: while failure of ORF has a known clinical manifestation (reality confusion as evident in confabulation and disorientation), the failure of TOJ, as tested here, has no such known clinical correlate.