Neuroscience
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Potocki-Shaffer Syndrome is a rare neurodevelopmental syndrome associated with microdeletion of a region of Chromosome 11p11.2. Genetic evidence has implicated haploinsufficiency of PHF21A, a gene that encodes a histone-binding protein, as the likely cause of intellectual disability and craniofacial abnormalities in Potocki-Shaffer Syndrome. However, the molecular consequences of reduced PHF21A expression remain elusive. ⋯ Finally, PHF21A-deficient patient-derived cells exhibited a delayed induction of immediate early genes following forskolin stimulation. These results suggest that an impaired response to cAMP signaling might be involved in the pathology of PHF21A deficiency. This article is part of a Special Issue entitled: [SI: Molecules & Cognition].
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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 cognitive impairment characterizing the phenotype of older adults has been related to the efficiency of the antioxidant system. This study aimed at investigating the effect of memory training (MT) on memory, global cognitive functioning, and the oxidant and antioxidant capacity of plasma. We recruited 52 healthy subjects aged over 60. ⋯ When we considered the Δvalue (Δvariable = variable post-MT minus variable pre-MT) in EG, the ΔMMSE and ΔLTM scores were negatively associated to Δd-ROMs, and positively to ΔBAP and ΔBAP/dROM. In conclusion, our results suggest that MT improves memory and global cognitive functioning. These processes were significantly associated to increase in resistance against oxidative stress at the plasma level in healthy older adults.
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Memory functions can be considerably affected by various life events and stress has shown to be a chief regulator. Different stress patterns have distinct effects on the overall functioning of the brain. Stress provokes inflammation not only in the periphery but also in the brain. ⋯ Results from the forced swim test, elevated plus maze test and Morris water maze test showed significant effects of NSAIDs. A significant decrease in plasma corticosterone and increased DA and 5-HT levels were observed in NSAID-treated dissimilar-stressed rats. This study demonstrates the therapeutic potential of NSAIDs for dissimilar stress-induced depressive behaviors and impaired memory functions and related hormonal and neurochemical changes in the rat brain.
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Accumulation of amyloid-β (Aβ) is widely believed to be an early event in the pathogenesis of Alzheimer's disease (AD). Kv4 is an A-type K+ channel, and our previous report shows the degradation of Kv4, induced by the Aβ42 accumulation, may be a critical contributor to the hyperexcitability of neurons in a Drosophila AD model. Here, we used well-established courtship memory assay to investigate the contribution of the Kv4 channel to short-term memory (STM) deficits in the Aβ42-expressing AD model. ⋯ Furthermore, the STM phenotypes can be rescued, at least partially, by restoration of Kv4 expression in Aβ42 flies, indicating the STM deficits could be partially caused by Kv4 degradation. In addition, IA is significantly decreased in MB neurons (MBNs) but not in PNs, suggesting Kv4 degradation in MBNs, in particular, plays a critical role in courtship STM loss in Aβ42 flies. These data highlight causal relationship between region-specific Kv4 degradation and age-dependent learning decline in the AD model, and provide a mechanism for the disturbed cognitive function in AD.