Astrocytes are the most abundant cell type in the brain and they make close contacts with neurons and blood vessels. They respond dynamically to various environmental stimuli and change their morphological and functional properties. Both physiological and pathological stimuli can induce versatile changes in astrocytes, as this phenomenon is referred to as 'astrocytic plasticity'. However, the molecular and cellular mechanisms of astrocytic plasticity in response to various stimuli remain elusive, except for the presence of hypertrophy, a conspicuous structural change which is frequently observed in activated or reactive astrocytes. Here, we investigated differential characteristics of astrocytic plasticity in a stimulus-dependent manner. Strikingly, a stab wound brain injury lead to hypertrophy of astrocytes accompanied by increased GABA expression and tonic GABA release in mouse CA1 hippocampus. In contrast, the mice experiencing enriched environment exhibited astrocytic hypertrophy with enhanced proBDNF immunoreactivity but without GABA signal. Based on the results, we define proBDNF-positive/GABA-negative hypertrophic astrocytes as 'active' astrocytes and GABA-positive hypertrophic astrocytes as 'reactive' astrocytes, respectively. We propose for the first time that astrocytic proBDNF can be a bona fide molecular marker of the active astrocytes, which are distinct from the reactive astrocytes which show hypertrophy but with aberrant GABA.
Bibliographical noteFunding Information:
This research was supported by Creative Research Initiative Program, Korean National Research Foundation (NRF) (2015R1A3A2066619), the Brain Research Program through NRF funded by the Ministry of Science and ICT (2018M3C7A1056682) and the Grant (2E28411) from Korea Institute of Science and Technology (KIST) (CJL). This study was also supported by the NRF-2016M3C7A1904233 and the Grant (2E26663) from KIST (HR).
© Experimental Neurobiology 2018.
All Science Journal Classification (ASJC) codes
- Clinical Neurology
- Cellular and Molecular Neuroscience