Neuroscience
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The delayed rectifier voltage-gated potassium channel Kv2.1 underlies a majority of the somatic K(+) current in neurons and is particularly important for regulating intrinsic neuronal excitability. Various stimuli alter Kv2.1 channel gating as well as localization of the channel to cell-surface cluster domains. ⋯ Further, we demonstrate that the C-terminus of Kv2.1 is not necessary for steady-state gating, sensitivity to intracellular phosphatase or NMDA-dependent modulation, though this region is required for localization of Kv2.1 to clusters. Thus, the molecular determinants of Kv2.1 localization and modulation are distinct regions of the channel that function independently.
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Histamine acts centrally to increase energy expenditure and reduce body weight by mechanisms not fully understood. It has been suggested that in the obese state hypothalamic histamine signaling is altered. Previous studies have also shown that histamine acting in the preoptic area controls thermoregulation. ⋯ Similarly, the ability of preoptic histamine signaling to increase the expression of uncoupling proteins was abolished. We also found that the expression of mRNA encoding the H1 receptor subtype in the preoptic area was significantly lower in obese animals. These results indicate that histamine signaling in the preoptic area modulates energy homeostasis by regulating body temperature, metabolic parameters and food intake and that the obese state is associated with a decrease in neurotransmitter's influence.
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Chronic systemic inflammation induces age-dependent differential phenotypic changes in microglia and astrocytes, yielding an anti-inflammatory cell phenotype in young rats and a proinflammatory cell phenotype in middle-aged rats. These observations prompted further investigation of the functional outcomes of the resultant differential microglial phenotypic changes. The present study examined the effects of age-dependent differential microglial phenotypic changes following chronic systemic inflammation on the formation of the post-tetanic potentiation (PTP) and long-term potentiation (LTP) in the hippocampus. ⋯ Minocycline, a known inhibitor of microglial activation, was systemically administered to middle-aged AA rats significantly restoring the mean magnitudes of both PTP and LTP. The mean expression levels of ED1 and IL-1β were significantly suppressed. These observations strongly suggest that chronic systemic inflammation induces deficits in the hippocampal LTP in middle-aged rats through neuroinflammation mainly induced by microglia.
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The angiotensin II receptor subtype 2 (AT2-R) has been proposed to mediate protective vascular actions after brain injury. In this study we investigated the participation of this peptide in the tolerance to cellular damage induced by preconditioning in a rat model of neonatal hypoxia-ischemia (HI). We found that injured animals present a decreased number of microvessels in the ipsilateral (IPLT) side of the brain while in the contralateral (CNLT) side the microvessel number is increased. ⋯ However these vessels show a remarkable increase of the fluorescent signal when they are labeled with antiFlk-1 (VEGFR2), while the Flt-1 (VEGFR1) signal faded in both the injured and the preconditioned animals. The pharmacological blockade of the AT2-R by the drug PD123319 (1.69 mM in the lateral ventricle) diminished the resilience of the microvasculature to HI injury provided by preconditioning and also the Flk-1 increase that occurred in these animals. In conclusion these results suggest an interaction of the AT2-R with VEGFR2 in the neonatal brain microvasculature that produces protective effects which are associated with injury tolerance.
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The long-term effects of stress during development have been well characterized. However, the effects of developmental stress on the underlying neurological mechanisms related to the reward system are not well understood. The present report studied the long term effects of stress during development on the structural plasticity in the cortical and subcortical regions. ⋯ MS resulted in an increase in dendritic growth and spine density in the subregions of the PFC. The effect of PS on neuroanatomy was more robust than MS despite the shorter duration and intensity. The altered dendritic growth and spine density associated with stress during development could have potential impact on NAc and PFC related behaviors.