Long-term chemogenetic activation of M1 glutamatergic neurons attenuates the behavioral and cognitive deficits caused by intracerebral hemorrhage.

Journal Article (Journal Article)

Acute spontaneous intracerebral hemorrhage (ICH) is a life-threatening disease. It is often accompanied by severe neurological sequelae largely caused by the loss of integrity of the neural circuits. However, these neurological sequelae have few strong medical interventions. Designer receptors exclusively activated by designer drugs (DREADDs) are important chemogenetic tools capable of precisely modulating the activity of neural circuits. They have been suggested to have therapeutic effects on multiple neurological diseases. Despite this, no empirical research has explored the effects of DREADDs on functional recovery after ICH. We aimed to explore whether the long-term excitation of glutamatergic neurons in primary motor cortex (M1) by DREADD could promote functional recovery after ICH. We used CaMKII-driven Gq/Gi-DREADDs to activate/inhibit M1 glutamatergic neurons for 21 consecutive days, and examined their effects on behavioral and cognitive deficits caused by ICH in a mouse model of ICH targeting striatum. Long-term chemogenetic activation of the M1 glutamatergic neurons increased the spatial memory and sensorimotor ability of mice suffering from ICH. It also attenuated the mitochondrial dysfunctions of striatal neurons by raising the ATP levels and mitochondrial membrane potential while decreasing the 8-OHdG levels. These results strongly suggest that selective stimulation of the M1 glutamatergic neurons contributes to functional recovery after ICH presumably through alleviation of mitochondrial dysfunctions.

Full Text

Duke Authors

Cited Authors

  • Ling, W-Y; Cui, Y; Gao, J-L; Jiang, X-H; Wang, K-J; Tian, Y-X; Sheng, H-X; Cui, J-Z

Published Date

  • June 18, 2020

Published In

Volume / Issue

  • 527 / 1

Start / End Page

  • 22 - 28

PubMed ID

  • 32446371

Electronic International Standard Serial Number (EISSN)

  • 1090-2104

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2020.04.083

Language

  • eng

Conference Location

  • United States