Neuroscience
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Nuclear receptors (NR) are emerging as key players in the central nervous system (CNS) with reported implications in physiological and pathophysiological conditions. While a number of NR has been studied, it is unknown whether invalidation of the pregnane xenobiotic receptor (PXR, NR1I2) corresponds to neurological modifications in the adult brain. PXR-/- C57BL/6J and wild-type mice were used to investigate: (i) recognition memory, motor coordination, and anxiety-like behaviors; (ii) longitudinal video-electroencephalographic (EEG) recordings and frequency wave analysis; (iii) neurovascular structures by histological evaluation and expression of the cerebrovascular tight junctions ZO1 and CLDN5. ⋯ Neurophysiological changes did not correspond to significant structural changes in the adult brain, expect for a localized and minor increase in the fronto-parietal neurovascular density and reduced ZO1, but not CLDN5, expression in isolated brain capillaries. Our results converge with existing evidence supporting a link between NR expression and brain physiology. Although the exact modalities remain to be elucidated, the possibility that extra-physiological modulation of PXR may constitute a pathophysiological entry point or a molecular target for brain diseases is proposed.
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The biomarkers may be useful for predictive diagnosis of Alzheimer's disease (AD). The current challenge is to diagnose it in its preclinical phase. The combination of cerebrospinal fluid (CSF) biomarkers and imaging has been investigated extensively for a number of years. ⋯ In the first section, the results show the contribution of biomarkers to predict and track AD considered as classical biomarkers. In the second section, the results highlight the involvement of novel candidates that should be considered for future evaluation in the characterization of the AD progression. Reported findings open prospect to define noninvasive biomarkers to predict AD before symptoms onset.
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Posttraumatic stress and drug use disorders may stem from aberrant memory formation. As the endocannabinoid (eCB) system has a pivotal role in emotional memory processing and related synaptic plasticity, here we seek to review and discuss accumulating evidence on how and where in the brain interventions targeting the eCB system would attenuate outcomes associated with traumatic events and/or drug addiction through memory extinction facilitation or reconsolidation disruption. Currently available data from mouse, rat, monkey and healthy human studies investigating the effects of cannabinoid drugs on extinction and reconsolidation of aversive memories are more consistent than those related to rewarding drug-associated memories. ⋯ Brain areas in which cannabinoid drugs induce these effects include the prefrontal cortex, amygdala, hippocampus, and/or nucleus accumbens. The potential role of 2-arachidonoylglycerol (2-AG) and cannabinoid type-2 (CB2) receptors in emotional memory extinction and reconsolidation is currently under investigation. Overall, preclinical data support a closer look into certain cannabinoid drugs owing to their safety and potential therapeutic value against stress-related and drug use disorders.
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In this review we explore the role of the perirhinal cortex (Prh) in memory, focusing on the cellular and molecular mechanisms that have been described to happen in this structure. The Prh is part of the medial temporal lobe, but the evidences show that it has a different function than that of the hippocampus. ⋯ We discuss a series of studies of memory and plasticity in this region and how they might relate. In addition, we propose that Prh could play a role as a "pattern separator" for object memories, similar to the function of the dentate gyrus of the hippocampus in the spatial domain.
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Neuroimaging epigenetics is an interdisciplinary application of epigenetics to cognitive neuroscience that seeks to identify molecular and neural predictors of human behavior. This approach can be sensitive to the dynamic interaction between biological predisposition and environmental influences, and is potentially more informative than an approach using static genetic code. Recent work in this field has generated considerable enthusiasm, yet caution is warranted since any novel cross-disciplinary approach lacks a set of established conventions or standards. In this paper we review existing research in the field of imaging epigenetics, outline important caveats and considerations, and suggest a set of guidelines for researchers conducting this work.