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Upregulation of Striatal Metabotropic Glutamate Receptor Subtype 1 (mGluR1) in Rats with Excessive Glutamate Release Induced by N-Acetylcysteine

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Abstract

The aim of this study is to investigate the changes in expression of metabotropic glutamate (Glu) receptor subtype 1 (mGluR1), a key molecule involved in neuroexcitetoxicity, during excessive Glu release in the brain by PET imaging. An animal model of excessive Glu release in the brain was produced by intraperitoneally implanting an Alzet osmotic pump containing N-acetylcysteine (NAC), an activator of the cysteine/Glu antiporter, into the abdomen of rats. Basal Glu concentration in the brain was measured by microdialysis, which showed that basal Glu concentration in NAC-treated rats (0.31 µM) was higher than that in saline-treated rats (0.17 µM) at day 7 after the implantation of the osmotic pump. Similarly, PET studies with [11C]ITDM, a useful radioligand for mGluR1 imaging exhibited that the striatal binding potential (BPND) of [11C]ITDM for mGluR1 in PET assessments was increased in NAC-treated animals at day 7 after implantation (2.30) compared with before implantation (1.92). The dynamic changes in striatal BPND during the experimental period were highly correlated with basal Glu concentration. In conclusion, density of mGluR1 is rapidly upregulated by increases in basal Glu concentration, suggesting that mGluR1 might to be a potential biomarker of abnormal conditions in the brain.

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Acknowledgements

We would like to thank the staff at the National Institutes for Quantum and Radiological Science and Technology for their support with the cyclotron operation, radioisotope production, radiosynthesis, and animal experiments. We thank Barry Patel, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported by JSPS KAKENHI Grant Number JP19K08240 and AMED Moonshot Research and Development Program Grant Number 21zf0127003h001.

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Correspondence to Tomoteru Yamasaki.

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Yamasaki, T., Okada, M., Hiraishi, A. et al. Upregulation of Striatal Metabotropic Glutamate Receptor Subtype 1 (mGluR1) in Rats with Excessive Glutamate Release Induced by N-Acetylcysteine. Neurotox Res 40, 26–35 (2022). https://doi.org/10.1007/s12640-021-00449-4

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  • DOI: https://doi.org/10.1007/s12640-021-00449-4

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