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Original Article

Exp Neurobiol 2018; 27(3): 155-170

Published online June 30, 2018

https://doi.org/10.5607/en.2018.27.3.155

© The Korean Society for Brain and Neural Sciences

Astrocytic proBDNF and Tonic GABA Distinguish Active versus Reactive Astrocytes in Hippocampus

Heejung Chun1,2, Heeyoung An1,2,3, Jiwoon Lim2, Junsung Woo1, Jaekwang Lee1, Hoon Ryu4,5* and C. Justin Lee1,2,6*

1Center for Neuroscience and Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, 2Center for Glia-Neuron Interaction, Brain Science Institute, KIST, Seoul 02792, 3KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, 4Center for Neuromedicine, Brain Science Institute, KIST, Seoul 02792, Korea, 5Boston University Alzheimer’s Disease Center and Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA, 6Division of Bio-Medical Science & Technology, KIST School, KIST, Seoul 02792, Korea

Correspondence to: *To whom correspondence should be addressed.
C. Justin Lee, TEL: 82-2-958-6940, FAX: 82-2-958-6919
e-mail: cjl@kist.re.kr
Hoon Ryu, TEL: 1-857-364-5910, FAX: 1-857-364-4540
e-mail: hoonryu@bu.edu

Received: June 12, 2018; Revised: June 26, 2018; Accepted: June 30, 2018

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.

Graphical Abstract


Keywords: Astrocytes, gamma-Aminobutyric Acid, Cell Plasticity, Wounds, Stab, brain-derived neurotrophic factor precursor