Neuroscience
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Diabetic retinopathy, a leading cause of vision loss, was considered as a solely vascular disorder but some recent studies suggest that retinal neurons may be affected much before the appearance of vascular lesions. However, the cellular processes involved in diabetes-induced degeneration of retinal neurons are poorly understood. Calcium (Ca2+) signaling plays a key role in normal functioning of neurons, and its dysregulation may lead to degeneration of neurons. ⋯ The depolarization of mitochondrial membrane was more pronounced in the neurons of the inner nuclear layer of diabetic rats. The physiological changes in mitochondria were observed as early as 9 weeks post diabetes induction. Thus, we report here that the intracellular Ca2+ signaling and mitochondrial function in retinal neurons are altered at an early stage of diabetes.
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Myeloid-derived suppressor cells (MDSCs) have strong immunosuppressive characteristics, which allow them to limit inflammation and facilitate wound healing and recovery. Although MDSCs are a newly-determined cell type that is gaining attention in the immunology field, their neuroimmunological characteristics remain unstudied. ⋯ MDSCs are among the first responders to tissue injury, responding even prior to microglial activation. Positron emission tomography imaging of translocator protein results suggest that infiltrating MDSCs suppress neuronal inflammation and interact with resident immune cells, like microglia, following focal TBI.
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Ethanol ingestion by a mother during pregnancy entails adverse consequences for her offspring. In this study, adult female rats were given access to ethanol from 8 days prior to mating to post-parturition weaning, and the effects on her offspring were evaluated. We investigated changes in the cocaine- and amphetamine-regulated transcript peptide (CART), a neuropeptide involved in the central effects of ethanol in the frame of reward and stress processing circuits. ⋯ Their brains showed decreased CART-immunoreactivity in nucleus accumbens shell, lateral bed nucleus of stria terminalis, PVN, ARC, LH, hippocampus and LC as compared to age-matched control offspring. However, CART-immunoreactive profile in EW and fibers in VTA of 85-day-old offspring was similar to that in the control. Thus, regional imbalance in the CART system of the offspring of alcoholic dams seems correlated with the affective and emotional abnormalities and memory deficits.
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The over-activation of N-methyl-D-aspartate receptors (NMDARs) is the main cause of neuronal death in brain ischemia. Both the NMDAR and the Acid-sensing ion channel 1a (ASIC1a) are present in the postsynaptic membrane of the central nervous system (CNS) and participate in physiological and pathological processes. However, the specific role played by ASIC1a in these processes remains elusive. ⋯ Furthermore, brain infarct sizes were reduced by a greater degree in older mice compared to younger ones when ASIC1a activity was suppressed. These data suggest that ASIC1a activity selectively enhances the function of triheteromeric NMDARs and exacerbates ischemic neuronal death especially in older animal brains. We propose ASIC1a as a novel therapeutic target for preventing and reducing the detrimental effect of brain ischemia in humans.
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Mitochondrial dysfunction has been shown to play a major role in neurodegenerative disorders such as Huntington's disease, Alzheimer's disease and Parkinson's disease. In these and other neurodegenerative disorders, disruption of synaptic connectivity and impaired neuronal signaling are among the early signs. When looking for potential causes of neurodegeneration, specific attention is drawn to the function of synaptic mitochondria, as the energy supply from mitochondria is crucial for normal synaptic function. ⋯ We found higher mitochondrial oxygen consumption rate in both resting and activated cortical synaptosomes compared to striatal synaptosomes, especially when using pyruvate as a substrate. The higher oxygen consumption rate was not caused by differences in mitochondrial content, but instead corresponded with a higher proton leak in the cortical synaptic mitochondria compared to the striatal synaptic mitochondria. Our results show that the synaptic mitochondria of the striatum and cortex differently regulate respiration both in response to activation and variations in substrate conditions.