Region-Specific Characteristics of Astrocytes and Microglia: A Possible Involvement in Aging and Diseases

Abstract

Although different regions of the brain are dedicated to specific functions, the intra- and inter-regional heterogeneity of astrocytes and microglia in these regions has not yet been fully understood. Recently, an advancement in various technologies, such as single-cell RNA sequencing, has allowed for the discovery of astrocytes and microglia with distinct molecular fingerprints and varying functions in the brain. In addition, the regional heterogeneity of astrocytes and microglia exhibits different functions in several situations, such as aging and neurodegenerative diseases. Therefore, investigating the region-specific astrocytes and microglia is important in understanding the overall function of the brain. In this review, we summarize up-to-date research on various intra- and inter-regional heterogeneities of astrocytes and microglia, and provide information on how they can be applied to aging and neurodegenerative diseases.

Age-related changes in plasma extracellular vesicles influence neuroinflammation in the brain and neurological outcome after traumatic spinal cord injury

“…Comparisons between young and aged sham mice indicated genetic heterogeneity between cortex and hippocampus during aging. This is in agreement with a recent report that summarized the cellular and molecular heterogeneity of astrocytes and microglia in different brain regions in relation to aging and neurodegenerative diseases [24]. Through heatmap clustering of the average zscores for each group, our findings demonstrate that (1) the "Activated Microglia" and "Autophagy" are the top two upregulated pathways in the hippocampus, but not in the somatosensory cortex with aging, and (2) these pathways become pronounced following SCI in the cortex from aged but not young adult animals.…”

Microglia activity in the human basal ganglia is altered in alcohol use disorder and reversed with remission from alcohol

“…One possible source of these differences could be astrocyte densities which are known to differ in functions across brains regions. 57,58 Indeed, studies that have observed decrease in astrocytes in AUD are largely focused in brain regions where there are lower densities of astrocytes, 55,56,59 while the structures examined in the current study may have high densities of astrocytes; however, further investigation into astrocyte populations in the examined structures is needed. Importantly, it has been demonstrated that GFAP density does not change in rats chronically exposed to alcohol in the cerebellum.…”

“…However, the brain regions examined in these studies differed to the current study and were instead focused on the dorsolateral prefrontal cortex, orbitofrontal cortex and hippocampus, 54–56 and thus, like microglia (described above), astrocytes could demonstrate region‐specific responses to alcohol. One possible source of these differences could be astrocyte densities which are known to differ in functions across brains regions 57,58 . Indeed, studies that have observed decrease in astrocytes in AUD are largely focused in brain regions where there are lower densities of astrocytes, 55,56,59 while the structures examined in the current study may have high densities of astrocytes; however, further investigation into astrocyte populations in the examined structures is needed.…”

Secreted phosphoprotein 1 slows neurodegeneration and rescues visual function in mouse models of aging and glaucoma

“…Age-related changes are observed not only in neurons but also in glial cells. 11 – 13 RNA sequencing of purified astrocytes from various regions of the brain has demonstrated up-regulation of inflammatory markers, components of the complement cascade, factors involved in synapse elimination, and others that are similar to those observed in reactive astrocytes. 14 – 16 In the optic nerve head, astrocytes form the direct cellular environment of the unmyelinated RGC axons.…”