Details

Autor(en) / Beteiligte

• Danjo, Yosuke
• Shigetomi, Eiji
• Hirayama, Yukiho J
• Kobayashi, Kenji
• Ishikawa, Tatsuya
• Fukazawa, Yugo
• Shibata, Keisuke
• Takanashi, Kenta
• Parajuli, Bijay
• Shinozaki, Youichi
• Kim, Sun Kwang
• Nabekura, Junichi
• Koizumi, Schuichi

Titel

Transient astrocytic mGluR5 expression drives synaptic plasticity and subsequent chronic pain in mice

Ist Teil von

• The Journal of experimental medicine, 2022-04, Vol.219 (4)

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Activation of astrocytes has a profound effect on brain plasticity and is critical for the pathophysiology of several neurological disorders including neuropathic pain. Here, we show that metabotropic glutamate receptor 5 (mGluR5), which reemerges in astrocytes in a restricted time frame, is essential for these functions. Although mGluR5 is absent in healthy adult astrocytes, it transiently reemerges in astrocytes of the somatosensory cortex (S1). During a limited spatiotemporal time frame, astrocytic mGluR5 drives Ca2+ signals; upregulates multiple synaptogenic molecules such as Thrombospondin-1, Glypican-4, and Hevin; causes excess excitatory synaptogenesis; and produces persistent alteration of S1 neuronal activity, leading to mechanical allodynia. All of these events were abolished by the astrocyte-specific deletion of mGluR5. Astrocytes dynamically control synaptic plasticity by turning on and off a single molecule, mGluR5, which defines subsequent persistent brain functions, especially under pathological conditions.