Neuroscience
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The contribution of Dopamine (DA) to minimal hepatic encephalopathy (MHE) has been demonstrated. However, recent studies have revealed that cholesterol (CHO) treatment substantially increased the risk of dementia. The objectives of this study were to investigate whether CHO was induced by DA overload and its involvement in DA-induced cognitive impairment in MHE. ⋯ Memory impairments were observed in MHE/DA-treated rats, which were partially rescued by atorvastatin (ATVS) treatment, confirming the involvement of CHO burden in vivo. Overall, our study suggests that DA overload triggers obvious CHO production from astrocytes. Excessive CHO in turn triggered neurons to secrete abundant DA and DA burden in combination with CHO overload elicit the cognitive decline and memory loss via PPARγ/ERK/CREB pathway in MHE.
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DFNA2 is a progressive deafness caused by mutations in the voltage-activated potassium channel KCNQ4. Hearing loss develops with age from a mild increase in the hearing threshold to profound deafness. Studies using transgenic mice for Kcnq4 expressed in a mixed background demonstrated the implication of outer hair cells at the initial phase. ⋯ We also established that outer hair cell loss kinetics slowed down from basal to apical regions correlating with KCNQ4 expression pattern determined in wild-type mice. Our findings indicate that KCNQ4 plays differential roles in each cochlear cell-type impacting in their survival ability. Inner hair cell and spiral ganglion neuron death generates severe hearing loss that could be associated with the last phase of DFNA2.
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Excitotoxicity plays an important role in the pathogenesis of developing brain injury. The neuropeptide secretoneurin (SN) has neuroprotective potential. The aim of this study was to investigate SN plasma concentrations following excitotoxicity and to evaluate the effect of SN as therapeutic strategy in excitotoxic newborn brain injury. ⋯ Administration of SN did not positively affect lesion size, apoptotic cell death, microglial cell activation or cell proliferation. To conclude, endogenous SN plasma levels are lower in newborn mice subjected to an excitotoxic insult than in healthy controls. Supplementation with SN in various treatment regimens is not neuroprotective in the experimental animal model of excitotoxic newborn brain injury.
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The benefits of Cochlear implant (CI) technology depend among other factors on the proximity of the electrode array to the spiral ganglion neurons. Laminin, a component of the extracellular matrix, regulates Schwann cell proliferation and survival as well as reorganization of actin fibers within their cytoskeleton, which is necessary for myelination of peripheral axons. In this study we explore the effectiveness of laminin-coated electrodes in promoting neuritic outgrowth from auditory neurons towards the electrode array and the ability to reduce acoustic and electric auditory brainstem response (i.e. aABR and eABR) thresholds. ⋯ In vivo: Animals implanted with laminin-coated electrodes experience significant decreases in eABR and aABR thresholds at selected frequencies compared to the results from the uncoated electrodes group. At 1 month post implantation there were a greater number of spiral ganglion neurons and neuritic processes projecting into the scala tympani of animals implanted with laminin-coated electrodes compared to animals with uncoated electrodes. These data suggest that Schwann cells are attracted towards laminin-coated electrodes and promote neuritic outgrowth/ guidance and promote the survival of spiral ganglion neurons following electrode insertion trauma.
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Temporal lobe epilepsy (TLE) is the commonest of adult epilepsies, often refractory to antiepileptic medications, whose prevention and treatment rely on understanding basic pathophysiological mechanisms in interlinked structures of the temporal lobe. The medial entorhinal area (MEA) is affected in TLE but mechanisms underlying hyperexcitability of MEA neurons require further elucidation. Previous studies have examined the role of the presubiculum (PrS) in mediating MEA pathophysiology but not the juxtaposed parasubiculum (Par). ⋯ These neurons experience significant reductions in synaptic inhibition and perish under chronic epileptic conditions. Connectivity between brain regions was deduced through changes in excitatory and inhibitory synaptic drive to neurons recorded in one region upon focal application of glutamate followed by NBQX to neurons in another using a microfluidic technique called CESOP and TLE-related circuit reorganization was assessed using data from normal and epileptic animals. The region-specific changes in Par and neighboring PrS and MEA together with their unexpected interactions are of significance in identifying ictogenic cells and circuits within the parahippocampal region and in unraveling pathophysiological mechanisms underlying TLE.