Glutamine synthetase(GS)in astrocytes regulates glutamatergic neurotransmission by maintaining glutamate clearance in the brain.This study determined that GS in astrocytes of the caudate and putamen(CPu)regulates loco...Glutamine synthetase(GS)in astrocytes regulates glutamatergic neurotransmission by maintaining glutamate clearance in the brain.This study determined that GS in astrocytes of the caudate and putamen(CPu)regulates locomotor sensitization after repeated nicotine exposure.Nicotine increased phosphorylated c-Jun N-terminal kinase(pJNK)by stimulating α7 nicotinic acetylcholine receptors in cultured glioma C6 cells and primary astrocytes in a Ca^(2+)-dependent manner.Active JNK phosphorylated metabotropic glutamate receptor 1a(mGluR1a)at the carboxyl terminus of glutathione S-transferase-tagged mGluR1a in vitro.Interference with the pJNK-mGluR1a interaction using the inhibitory peptide,Tat-mGluR1a-i(10μmol/L),decreased the nicotine-induced increase in GS activity in glioma C6 cells and primary astrocytes.Similar results were obtained by bilateral intra-CPu infusion of the inhibitory peptide(2 nmol/side).Inhibition of GS activity by bilateral intra-CPu infusion of methionine sulfoximine(50 nmol/side)decreased the repeated nicotine-induced increase in locomotor activity.These findings suggest that astrocytes in the CPu upregulate locomotor sensitization by activating GS via the pJNK-mGluR1a interaction,which is linked to α7 nicotinic acetylcholine receptors in response to nicotine.展开更多
基金supported by the National Research Foundation(NRF-2021R1A2C2008083 to ESC,Korea)and(NRF-2020R1C1C1012561 to JHY,Korea).
文摘Glutamine synthetase(GS)in astrocytes regulates glutamatergic neurotransmission by maintaining glutamate clearance in the brain.This study determined that GS in astrocytes of the caudate and putamen(CPu)regulates locomotor sensitization after repeated nicotine exposure.Nicotine increased phosphorylated c-Jun N-terminal kinase(pJNK)by stimulating α7 nicotinic acetylcholine receptors in cultured glioma C6 cells and primary astrocytes in a Ca^(2+)-dependent manner.Active JNK phosphorylated metabotropic glutamate receptor 1a(mGluR1a)at the carboxyl terminus of glutathione S-transferase-tagged mGluR1a in vitro.Interference with the pJNK-mGluR1a interaction using the inhibitory peptide,Tat-mGluR1a-i(10μmol/L),decreased the nicotine-induced increase in GS activity in glioma C6 cells and primary astrocytes.Similar results were obtained by bilateral intra-CPu infusion of the inhibitory peptide(2 nmol/side).Inhibition of GS activity by bilateral intra-CPu infusion of methionine sulfoximine(50 nmol/side)decreased the repeated nicotine-induced increase in locomotor activity.These findings suggest that astrocytes in the CPu upregulate locomotor sensitization by activating GS via the pJNK-mGluR1a interaction,which is linked to α7 nicotinic acetylcholine receptors in response to nicotine.
