Neuroscience
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Neuregulin-1 (NRG1) plays an important role in the development and plasticity of the brain and exhibits potent neuroprotective properties. However, little information on its role in Alzheimer's disease (AD) is known. The neuroprotective effect and mechanisms of NRG1 in SH-SY5Y cells overexpressing the Swedish mutant form of amyloid precursor protein (Swe-APP) and primary cortical neuronal cells treated with amyloid beta peptide(1-42) (Aβ(1-42)) were investigated in this study. ⋯ NRG1 reduced the accumulation of reactive oxygen species and attenuated Swe-APP-induced mitochondrial membrane potential loss. NRG1 also induced the upregulation of the expression of the anti-apoptotic protein, Bcl-2, and decreased caspase-3 activation. Collectively, our results demonstrate that NRG1 exerts neuroprotective effects via the ErbB4 receptor, which suggests the neuroprotective potential of NRG1 in AD.
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Cranial parasympathetic outflow is mediated through the sphenopalatine ganglion (SPG). The present study was performed to examine the expression of the parasympathetic signaling transmitters and their receptors in human and rat SPG. Indirect immunofluorescence technique was used for the demonstration of vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP), nitric oxide synthase (NOS), glutamine synthetase (GS), glial fibrillary acidic protein (GFAP), VIP and PACAP common receptors (VPAC1, VPAC2), and PACAP receptor (PAC1). ⋯ Western blot revealed protein expression of PAC1, VPAC1, and VPAC2 in rat SPG. The trigeminal-autonomic reflex may be active in migraine attacks. We hypothesized that VIP, PACAP, NOS, PAC1, VPAC1, and VPAC2 play a role in the activation of parasympathetic cranial outflow during migraine attacks.
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Similar pattern of peripheral neuropathy in mouse models of type 1 diabetes and Alzheimer's disease.
There is an increasing awareness that diabetes has an impact on the CNS and that diabetes is a risk factor for Alzheimer's disease (AD). Links between AD and diabetes point to impaired insulin signaling as a common mechanism leading to defects in the brain. However, diabetes is predominantly characterized by peripheral, rather than central, neuropathy, and despite the common central mechanisms linking AD and diabetes, little is known about the effect of AD on the peripheral nervous system (PNS). ⋯ Phosphorylation of the insulin receptor and glycogen synthase kinase 3β (GSK3β) was similarly affected in insulin-deficient and APP transgenic mice despite significantly different blood glucose and plasma insulin levels, and nerve of both models showed accumulation of Aβ-immunoreactive protein. Although diabetes and AD have different primary etiologies, both diseases share many abnormalities in both the brain and the PNS. Our data point to common deficits in the insulin-signaling pathway in both neurodegenerative diseases and support the idea that AD may cause disorders outside the higher CNS.
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Rett syndrome (RTT) is an autism spectrum disorder caused by mutation in the gene encoding methyl CpG binding protein 2 (MECP2). Evidence to date suggests that these disorders display defects in synaptic organization and plasticity. A hallmark of the pathology in RTT has been identified as decreased dendritic arborization, which has been interpreted to represent abnormal dendritic formation and pruning during development. ⋯ We also failed to detect abnormalities in dendritic inputs at symptomatic stages when glomeruli from mutant mice appear smaller in area than the wild type (WT) (6 weeks postnatally). Collectively, these findings suggest that the initial defects in glomeruli impairment seen with Mecp2 mutation do not result from abnormal dendritic development. Our results using the olfactory system indicate that dendritic abnormalities are not an early feature in the abnormalities incurred by Mecp2 mutation.
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Vascular endothelial growth factor (VEGF) is neuroprotective and induces neurogenesis and angiogenesis when given early after traumatic brain injury (TBI). However, the effects of VEGF administration in the subacute phase after TBI remain unknown. Mice were subjected to TBI and treated with vehicle or VEGF beginning 7 days later for an additional 7 days. ⋯ VEGF treatment led to significant increments in cell proliferation (1.9 fold increase vs. vehicle, P<0.0001) and angiogenesis in the lesioned cortex (1.7 fold increase vs. vehicle, P=0.0001) but most of the proliferating cells differentiated into glia and no mature newly-generated neurons were detected. In conclusion, VEGF induces gliogenesis and angiogenesis when given 7 days post TBI. However, treated mice had only insignificant motor improvements in this paradigm, suggesting that the bulk of the beneficial effects observed when VEGF is given early after TBI results from the neuroprotective effects.