The glia doctrine: Addressing the role of glial cells in healthy brain ageing

Abstract

Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction.

The Potential Role of Astrocytes in Parkinson’s Disease (PD)

“…Neuron and astrocyte interactions are complex, and both are coupled together by gap junction connexins [15]. Astrocytes are also connected with other nearby astrocytes, with the help of gap junctions [17].…”

“…In electrophysiology, astrocytes are considered to be electrically non-excitable cells, with a constant resting membrane potential (−90mV) of specific physiological response to electrical stimulation [12,13].The trophic and structural role of astrocytes also contribute to the dynamic components of brain connectivity and function [11]. Astrocytes perform several important physiological functions, including physical and metabolic support of neurons, repairing neurons, ion and water homeostasis, chemical signal transmission, regulation of energy metabolism and neurogenesis, blood flow regulation, immune and oxidative stress defense, detoxification, acid-base balance, and reaction to injury in the brain [5,11,12,14,15]. They also contribute to the formation and maturation of synapses and receptor trafficking [12].…”

Parkinson's disease as a result of aging

“…Both cells may produce detrimental effects on neighboring neurons due to chronic production of pro-inflammatory agents (ROS, leukocyte-attracting cytokines, etc.). However, both cells may also provide structural, metabolic, and trophic support to neurons (Allen & Barres, 2009; Chung et al ., 2009; Nagelhus et al ., 2013). This ambivalent activity is hampering the study of the role of the glial cells in PD.…”

Long-Term Consumption of High-Fat Diet in Rats: Effects on Microglial and Astrocytic Morphology and Neuronal Nitric Oxide Synthase Expression

“…Morphological complexity and the number and span of processes are typically increased, with a concomitant upregulation of GFAP staining, which lends itself to quantitative morphological analysis (Kang et al 2014; Wilhelmsson et al 2006). Under gliotic conditions, baseline astrocytic functions are disrupted, due to decreased or shifted expression of crucial proteins (aquaporins, connexins, ion channels or neurotransmitter transporters, among others) (Nagelhus et al 2013). At the same time, gliotic astrocytes may directly contribute to tissue damage via local proinflammatory signaling (Dong and Benveniste 2001).…”