Neuroscience
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Rapid remodeling of neurons provides the brain with flexibility to adjust to environmental fluctuations. In Siberian hamsters, hippocampal dendritic morphology fluctuates across the day. To reveal the regulatory mechanism of diurnal remodeling of hippocampal neurons, we investigated the effects of light signals applied under different photoperiodic conditions on dendritic morphology. ⋯ Spine density of dentate gyrus (DG) dendrites was increased by a dark pulse in LD and spine density of CA1 basilar dendrites was decreased by a light pulse in SD. These results indicate that light signals induce rapid remodeling of dendritic morphology in a hippocampal subregion-specific manner. A light pulse in SD decreased hippocampal expression of fetal liver kinase 1 (Flk1), a receptor for vascular endothelial growth factor (VEGF), raising the possibility that VEGF-FLK1 signaling might be involved in the rapid decrease of branching or spine density of CA1 basilar dendrites by light.
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Deep-brain stimulation at high frequencies (HFS) directed to the subthalamic nucleus (STN) is used increasingly to treat patients with Parkinson's disease. However, the mechanism of action by which HFS of the STN achieves its therapeutic effects remains unresolved. Insofar as lesions of the STN have similar therapeutic benefit, a favored hypothesis is that HFS acts by suppressing neural activity in the STN. ⋯ Finally, we demonstrated, in the absence of ether treatment, that HFS and chemical stimulation of the STN with local injections of kainic acid both induced c-fos expression in the globus pallidus, entopeduncular nucleus and substantia nigra. Together these results suggest that the principal action of STN stimulation at high frequencies is to excite rather than inhibit its efferent targets. Given that Parkinsonism has been associated with increased levels of inhibitory output activity from the basal ganglia, it is unlikely that excitation of output structures revealed in this study provides a basis for deep-brain stimulation's therapeutic action.
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We have shown that intravenous immunoglobulin (IVIG) contains anti-Aβ autoantibodies and IVIG could induce beta amyloid (Aβ) efflux from cerebrospinal fluid (CSF) to blood in both Multiple Sclerosis (MS) and Alzheimer disease (AD) patients. However, the molecular mechanism underlying IVIG-induced Aβ efflux remains unclear. In this study, we used amyloid precursor protein (AβPP) transgenic mice to investigate if the IVIG could induce efflux of Aβ from the brain and whether low-density lipoprotein receptor-related protein-1 (LRP1), a hypothetic Aβ transporter in blood-CSF barrier (BCB); could mediate this clearance process. ⋯ In the mechanistic study, IVIG could induce Aβ efflux through the in vitro BCB membrane formed by cultured BCB epithelial cells. Both receptor-associated protein (RAP; a functional inhibitor of LRP1), and LRP1 siRNA were able to significantly inhibit the Aβ efflux. Should Aβ prove to be the underlying cause of AD, our results strongly suggest that IVIG could be beneficial in the therapy for AD by inducing efflux of Aβ from the brain through the LRP1 in the BCB.
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We tested the hypothesis that the angiotensinergic neurotransmission, specifically in the paraventricular nucleus of the hypothalamus (PVN), is involved in the cardiovascular modulation during acute restraint stress (RS) in rats. The intravenous pretreatment with the angiotensin AT1 receptor antagonist losartan (5mg/kg) inhibited the pressor response to RS, but did not affect the concomitant RS-evoked tachycardiac response. Because similar effects were observed after the PVN pretreatment with CoCl2, and considering the high density of angiotensin receptors reported in the PVN, we studied the effect of the pretreatment of the PVN with either losartan or the angiotensin-converting enzyme (ACE) inhibitor lisinopril on the RS-evoked cardiovascular response. ⋯ When animals were pretreated with such doses of either losartan or lisinopril, the cardiovascular RS-evoked response was not affected, thus indicating that even if there were a complete leakage of the drug to the periphery, it would not affect the cardiovascular response to RS. This observation favors the idea that the effect of the intravenous injection of 5mg/kg of losartan on the RS-related cardiovascular response would be explained by an action across the blood-brain barrier, possibly in the PVN. In conclusion, the results suggest that an angiotensinergic neurotransmission in the PVN acting on AT1-receptors modulates the vascular component of the RS-evoked cardiovascular response.
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Although intracerebral hemorrhage (ICH) increases the level of glutamate in the perihematomal area and cerebral spinal fluid (CSF) in the ICH acute phase, it is unclear whether elevated glutamate activates neuronal nitric oxide synthase (nNOS) in the ICH brain and whether nNOS is an important target for ICH treatment. Here, we assessed the role of the nNOS inhibitor S-methyl-l-thiocitrulline (SMTC) in the activity of NADPH-d and ICH-induced brain injuries. An autologous blood intracerebral infusion model in male rats was used. ⋯ The loss of laminin- and occludin-stained vessels was significant in perihematomal regions after 24h of ICH and was significantly attenuated by the administration of SMTC (p<0.01 for laminin, p<0.05 for occluding, compared with the ICH group). Neuronal death and neurological deficits after ICH were also decreased in SMTC treatment rats (p<0.01, vs. the ICH group). The results suggest that the administration of the nNOS inhibitor SMTC after ICH protects against ICH-induced brain injuries and improves neurological function.