Neurochemical research
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Neurochemical research · Dec 2015
ReviewExcitable Astrocytes: Ca(2+)- and cAMP-Regulated Exocytosis.
During neural activity, neurotransmitters released at synapses reach neighbouring cells, such as astrocytes. These get excited via numerous mechanisms, including the G protein coupled receptors that regulate the cytosolic concentration of second messengers, such as Ca(2+) and cAMP. The stimulation of these pathways leads to feedback modulation of neuronal activity and the activity of other cells by the release of diverse substances, gliosignals that include classical neurotransmitters such as glutamate, ATP, or neuropeptides. ⋯ This is considered an adaptation to regulate homeostatic processes in a slow time domain as is the case in the endocrine system (slower than the nervous system), hence glial functions constitute the gliocrine system. This article provides an overview of the mechanisms of excitability, involving Ca(2+) and cAMP, where the former mediates phasic signalling and the latter tonic signalling. The molecular, anatomic, and physiologic properties of the vesicular apparatus mediating the release of gliosignals is presented.
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The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular tunnels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system. Besides waste elimination, the glymphatic system also facilitates brain-wide distribution of several compounds, including glucose, lipids, amino acids, growth factors, and neuromodulators. ⋯ Since the concept of the glymphatic system is relatively new, we will here review its basic structural elements, organization, regulation, and functions. We will also discuss recent studies indicating that glymphatic function is suppressed in various diseases and that failure of glymphatic function in turn might contribute to pathology in neurodegenerative disorders, traumatic brain injury and stroke.