Neuroscience
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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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Alzheimer's disease (AD) is the neurodegenerative disorder with no cure. Recent studies suggest that dysregulated postsynaptic store-operated calcium entry (nSOCE) may underlie mushroom spine loss that is related to AD pathology. ⋯ We further established that nSOCE antagonist EVP4593 decreases PSEN1ΔE9-mediated nSOCE upregulation and rescues mushroom spines in PSEN1ΔE9-expressing neurons. Obtained results further highlight the connection between dysregulation of endoplasmic reticulum calcium signaling and synaptic loss in AD and suggest that calcium signaling modulators may have a therapeutic value for treatment of memory loss in AD.
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Medullary dorsal horn (MDH), the homolog of spinal dorsal horn, plays essential roles in processing of nociceptive signals from orofacial region toward higher centers, such as the ventral posteromedial thalamic nucleus (VPM) and parafascicular thalamic nucleus (Pf), which belong to the sensory-discriminative and affective aspects of pain transmission systems at the thalamic level, respectively. In the present study, in order to provide morphological evidence for whether neurons in the MDH send collateral projections to the VPM and Pf, a retrograde double tracing method combined with immunofluorescence staining for substance P (SP), SP receptor (SPR) and Fos protein was used. Fluoro-gold (FG) was injected into the VPM and the tetramethylrhodamine-dextran (TMR) was injected into the Pf. ⋯ It was also found that some of the FG/TMR double-labeled neurons within lamina I expressed SPR and were in close contact with SP-immunoreactive (SP-ir) terminals. After formalin injection into the orofacial region, 41.4% and 34.3% of the FG/TMR double-labeled neurons expressed Fos protein in laminae I and III, respectively. The present results provided morphological evidence for that some SPR-expressing neurons within the MDH send collateral projections to both VPM and Pf and might be involved in sensory-discriminative and affective aspects of acute orofacial nociceptive information transmission.
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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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Neuropeptide Y is a peptide neuromodulator with protective roles including anxiolytic and antidepressant-like effects in animal models of depression and post-traumatic stress disorder. The lateral habenula (LHb) is a brain region that encodes aversive information and is closely related with mood disorders. Although LHb neurons express NPY receptors, the physiological roles of NPY in this region remain uninvestigated. ⋯ Inhibitory transmission remained unchanged by NPY application in a subset of neurons but was reduced in the majority of LHb neurons recorded. The overall outcome of NPY application was a decrease in the spontaneous firing rate of the LHb, leading to hypoactivation of the LHb. Our observations indicate that although NPY has divergent effects on excitatory and inhibitory transmission, NPY receptor activation decreases LHb activity, suggesting that the LHb may partly mediate the protective roles of NPY in the central nervous system.