Neuroscience
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The subiculum is the output component of the hippocampal formation and holds a key position in the neural circuitry of memory. Previous studies have demonstrated the subiculum's connectivity to other brain areas in detail; however, little is known regarding its internal structure. We investigated the cytoarchitecture of the temporal and mid-septotemporal parts of the subiculum using immunohistochemistry. ⋯ Quantitative analyses of the size and numerical density of somata substantiated this delineation. Both the proximal-distal division and five-layered structure in the subiculum 2 were confirmed throughout the temporal two-thirds of the subiculum. These findings will provide a new structural basis for hippocampal investigations.
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The leading treatments for severe hearing disabilities work on the principle of conveying electrical pulses to the auditory brainstem that enable perception of speech. It is currently not known how well the brainstem neurons specialized for decoding such coarse sound information develop when deprived of auditory input activity. Here, we used congenitally deaf α1D(-/-) mice, lacking activity in the auditory nerve, to investigate the superior paraolivary nucleus (SPON) - a prominent mammalian brainstem structure that responds selectively to sound pulses by rebound spiking. ⋯ We found the soluble form of the neurotrophic factor neuritin to be up-regulated in SPON of deaf mice, which may have promoted neuronal survival and prolonged plasticity of the SPON circuitry. A stereotyped timeline of compensation of rebound spiking in deaf SPON neurons indicates robust intrinsic regulation of the brainstem circuitry encoding sound rhythms. This may be a prerequisite for successful cochlear implants.
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Treatment strategies for ischemic stroke are still limited, since numerous attempts were successful only in preclinical research but failed under clinical condition. To overcome this translational roadblock, clinical relevant stroke models should consider co-morbidities, age-related effects and the complex neurovascular unit (NVU) concept. The NVU includes neurons, vessels and glial cells with astrocytic endfeet in close relation to the extracellular matrix (ECM). ⋯ Additional qualitative analyses demonstrated ischemia-induced loss of PNs and allocated neuropil ECM immunoreactive for aggrecan and neurocan, and impaired immunoreactivity for calbindin, the potassium channel subunit Kv3.1b and the glutamate decarboxylase isoforms GAD65 and GAD67 in the NRT. In conclusion, these data confirm PNs as highly sensitive constituents of the ECM along with impaired neuronal integrity of GABAergic neurons. Therefore, specific targeting of ECM components might appear as a promising strategy for future treatment strategies in stroke.
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Brain-blood barrier (BBB) disruption results in vasogenic edema, which is involved in the pathogenesis of epilepsy. Following status epilepticus (SE), up-regulated transient receptor potential canonical channel-3 (TRPC3), a Ca(2+)-permeable cation channels in endothelial cells, is relevant to vasogenic edema formation in the rat piriform cortex. In addition, pyrazole-3 (Pyr-3, a TRPC3 inhibitor) attenuated SE-induced vasogenic edema. ⋯ In addition, Pyr-3 mitigated NFκB p65-Thr435 phosphorylation induced by recombinant TNF-α. These findings indicate that TNF-α-mediated NFκB p65-Thr435 phosphorylation may up-regulate TRPC3 expression, which participates in vasogenic edema formation via increasing endothelial nitric oxide synthase expression following SE, independent of ETB receptor activation. Therefore, we suggest that TRPC3 may be involved in a positive feedback loop of NFκB/ETB receptor signaling pathway.
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The G-protein coupled receptor 6 (GPR6) is a constitutive active orphan GPCR which is predominantly expressed in striatopallidal neurons. GPR6 deficiency in mice may alter the susceptibility of the nigrostriatal dopaminergic system relevant for Parkinson's disease (PD). Here, we investigated the effect of GPR6 deficiency in mice on neurotoxicity induced by the dopaminergic neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). ⋯ Furthermore, the MPP(+)-induced dopamine release was significantly higher in GPR6(-/-)-mice. In conclusion, we showed that MPTP induces an enhanced dopaminergic neurodegeneration in GPR6(-/-)-mice indicated by alterations at the striatal and nigral level. We propose that GPR6 signaling is involved in the cascade of neurodegenerative events of the parkinsonian neurotoxin MPTP and suggest that pharmacological modulation of GPR6 might represent an entry point to further investigate GPR6 in PD.