Neuroscience
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Focal malformations of cortical development (FMCD) are highly associated with several neurological disorders including intractable epilepsy and neurocognitive disabilities. Over the past decade, several FMCD subtypes have been linked to hyperactivation of the mammalian target of rapamycin (mTOR) signaling cascade. ⋯ These mechanisms have been directly linked to mTOR activation. Perhaps most compelling, pharmacological inhibition of mTOR has been implemented successfully in clinical trials for select FMCD and provides a new vista for treatment.
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High levels of homocysteine (Hcy), known as hyperhomocysteinemia are associated with neurovascular diseases. H2S, a metabolite of Hcy, has potent anti-oxidant and anti-inflammatory activities; however, the effect of H2S has not been explored in Hcy (IC)-induced neurodegeneration and neurovascular dysfunction in mice. Therefore, the present study was designed to explore the neuroprotective role of H2S on Hcy-induced neurodegeneration and neurovascular dysfunction. ⋯ The increased expression of matrix metalloproteinase (MMP) MMP9, MMP2 and decreased expression of tissue inhibitor of metalloproteinase (TIMP) TIMP-1, TIMP-2, tight junction proteins (zonula occulden 1) in Hcy-treated group indicate neurovascular remodeling. Interestingly, NaHS treatment significantly attenuated Hcy-induced oxidative stress, memory deficit, neurodegeneration, neuroinflammation and cerebrovascular remodeling. The results indicate that H2S is effective in providing protection against neurodegeneration and neurovascular dysfunction.
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Hypoxic insults during the perinatal period lead to motor and cognitive impairments that later appear during childhood. In the adult brain, hypoxic events often lead to necrotic neuronal death, depending on the region and intensity of the event. During development an active apoptotic cell death occurs and could be an important variable affecting the hypoxic insult outcome. ⋯ In addition we analyzed the influence of retinal ganglion cells (RGC) in neuronal survival. Transection of RGC fibers at embryonic day (ED) 3 did not induce any change in developmental and HxCD at ED12. In conclusion, our findings demonstrate that a hypoxic insult in the developing brain triggers the same apoptotic pathway as the active developmental death.
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Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. ⋯ These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain.
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Early blindness results in occipital cortex neurons responding to a wide range of auditory and tactile stimuli. These changes in tuning properties are accompanied by an extensive reorganization of the occipital cortex that includes alterations in anatomical structure, neurochemical and metabolic pathways. ⋯ Here, using (1)H magnetic resonance spectroscopy in nine early blind and normally sighted subjects, we find that early blindness is associated with higher levels of creatine, choline and myo-Inositol and indications of lower levels of GABA within the occipital cortex. These results suggest that the cross-modal responses associated with early blindness may, at least in part, be driven by changes within occipital biochemical pathways.