Neuroscience
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Evidence suggests that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, may reduce the risk of Alzheimer's disease (AD). Statin action in patients with AD, as in those with heart disease, is likely to be at least partly independent of the effects of statins on cholesterol. Statins can alter cellular signaling and protein trafficking through inhibition of isoprenylation of Rho, Cdc42, and Rab family GTPases. ⋯ We utilized two-dimensional gel electrophoresis approaches to directly monitor the levels of isoprenylated and non-isoprenylated forms of Rho and Rab family GTPases. We report that simvastatin significantly inhibits RhoA and Rab4, and Rab6 isoprenylation at doses as low as 50nM in vitro. We also provide the first in vivo evidence that statins inhibit the isoprenylation of RhoA in the brains of rats and RhoA, Cdc42, and H-Ras in the brains of mice treated with clinically relevant doses of simvastatin.
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Microglia are present throughout the central nervous system (CNS) and express receptors for every known neurotransmitter. During inflammation, microglia change into a state that either promotes removal of debris (M1), or into a state that promotes soothing (M2). Caudal- and rostral- ventrolateral medullary regions (CVLM and RVLM, respectively) of the brainstem are key nuclei involved in all aspects of the cardiovascular system. ⋯ Induction of acute hypotension for 6h causes microglia to reduce the number of synaptic contacts by >20% in both, CVLM and RVLM, nuclei of the brainstem. Our analysis of the morphological characteristics of microglia, and expression levels of M1 and M2, reveals that the changes induced in microglial behavior do not require any obvious dramatic changes in their morphology. Taken together, our findings suggest that microglia play a novel, unexpected, physiological role in the uninjured autonomic nuclei of CNS; we therefore speculate that microglia act cooperatively with brainstem cardiovascular neurons to maintain them in a physiologically receptive state.
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The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia (ICG) for regional cardiac control. ⋯ Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) ICG contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial ICG contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT; (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG neurons could help in better understanding the function of the intrinsic cardiac nervous system.
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The capacity to flexibly switch between different task rules has been previously associated with distributed fronto-parietal networks, predominantly in the left hemisphere for phasic switching sub-processes, and in the right hemisphere for more tonic aspects of task-switching, such as rule maintenance and management. It is thus likely that the white matter (WM) connectivity between these regions is critical in sustaining the flexibility required by task-switching. This study examined the relationship between WM microstructure in young adults and task-switching performance in different paradigms: classical shape-color, spatial and grammatical tasks. ⋯ No association was found with behavioral measures obtained in the grammatical task-switching paradigm. The switch costs, a measure of phasic switching processes, were not correlated with WM microstructure in any task. This study shows that a more efficient inter-hemispheric connectivity within the frontal lobes favors sustained task-switching processes, especially with task contexts embedding non-verbal components.
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Kynurenine pathway metabolites (KPM) are thought to be synthesized mainly by non-neuronal cells in the mammalian brain. KPM are of particular interest because several studies demonstrated their implication in various disorders of the nervous system. Among KPM is xanthurenic acid (XA) deriving from the catabolism of 3-hydroxykynurenine. ⋯ Our results also reveal that XA-like immunoreactivity is not expressed by glial cells. To double-check our findings, we have also used another XA antibody obtained from a commercial source to confirm the neuronal expression of XA. Together, our results suggest that, differently to several other KPM produced by glial cells, XA exhibits a neuronal distribution in the mouse brain.