김형일 (GIST) | 한빛사논문 > 한빛사

한빛사논문

조회276

김형일Hyoung-Ihl Kim

GIST

Exp. Mol. Med., May 17 2024, | https://doi.org/10.1038/s12276-024-01232-z Tonic excitation by astrocytic GABA causes neuropathic pain by augmenting neuronal activity and glucose metabolism

Yeon Ha Ju^1,6, Jongwook Cho^2,6, Ji-Young Park², Hyunjin Kim¹, Eun-Bin Hong¹, C. Justin Lee³, Euiheon Chung², Hyoung-Ihl Kim^2,4 and Min-Ho Nam^1,5

¹Center for Brain Function, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.

²Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.

³Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, Republic of Korea.

⁴Department of Neurosurgery, Presbyterian Medical Center, Jeonju 54987, Republic of Korea.

⁵Department of KHU-KIST Convergence Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea.

⁶These authors contributed equally: Yeon Ha Ju, Jongwook Cho.

Corresponding authors

Correspondence to Hyoung-Ihl Kim or Min-Ho Nam.

Abstract

Neuropathic pain is a debilitating condition caused by the hyperexcitability of spinal dorsal horn neurons and is often characterized by allodynia. Although neuron-independent mechanisms of hyperexcitability have been investigated, the contribution of astrocyte-neuron interactions remains unclear. Here, we show evidence of reactive astrocytes and their excessive GABA release in the spinal dorsal horn, which paradoxically leads to the tonic excitation of neighboring neurons in a neuropathic pain model. Using multiple electrophysiological methods, we demonstrated that neuronal hyperexcitability is attributed to both increased astrocytic GABA synthesis via monoamine oxidase B (MAOB) and the depolarized reversal potential of GABA-mediated currents (E _GABA) via the downregulation of the neuronal K ⁺/Cl ^- cotransporter KCC2. Furthermore, longitudinal 2-deoxy-2-[ ¹⁸F]-fluoro-D-glucose microPET imaging demonstrated increased regional glucose metabolism in the ipsilateral dorsal horn, reflecting neuronal hyperexcitability. Importantly, inhibiting MAOB restored the entire astrocytic GABA-mediated cascade and abrogated the increased glucose metabolism and mechanical allodynia. Overall, astrocytic GABA-mediated tonic excitation is critical for neuronal hyperexcitability, leading to mechanical allodynia and neuropathic pain.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-20)
연구진국내 연구진
분야 생명과학 > 신경생물학

댓글 작성 로그인

CV 열람하기

연락처 보기