Published online Oct 19, 2021. doi: 10.5498/wjp.v11.i10.830
Peer-review started: February 28, 2021
First decision: March 30, 2021
Revised: April 11, 2021
Accepted: August 3, 2021
Article in press: August 3, 2021
Published online: October 19, 2021
Dopaminergic neurotoxicity is characterized by damage and death of dopaminergic neurons. Parkinson's disease (PD) is a neurodegenerative disorder that primarily involves the loss of dopaminergic neurons in the substantia nigra. Therefore, the study of the mechanisms, as well as the search for new targets for the prevention and treatment of neurodegenerative diseases, is an important focus of modern neuroscience. PD is primarily caused by dysfunction of dopaminergic neurons; however, other neurotransmitter systems are also involved. Research reports have indicated that the glutamatergic system is involved in different pathological conditions, including dopaminergic neurotoxicity. Over the last two decades, the important functional interplay between dopaminergic and glutamatergic systems has stimulated interest in the possible role of metabotropic glutamate receptors (mGluRs) in the development of extrapyramidal disorders. However, the specific mechanisms driving these processes are presently unclear. The participation of the universal neuronal messenger nitric oxide (NO) in the mechanisms of dopaminergic neurotoxicity has attracted increased attention. The current paper aims to review the involvement of mGluRs and the contribution of NO to dopaminergic neurotoxicity. More precisely, we focused on studies conducted on the rotenone-induced PD model. This review is also an outline of our own results obtained using the method of electron paramagnetic resonance, which allows quantitation of NO radicals in brain structures.
Core Tip: Dopaminergic neurotoxicity is characterized by damage and death of dopaminergic neurons. Chronic systemic exposure to rotenone (an inhibitor of mitochondrial complex I and a commonly used pesticide) induced dopaminergic degeneration and reproduced many features of human Parkinson's disease in rats. The current paper aims to review the involvement of metabotropic glutamate receptors and the contribution nitric oxide to dopaminergic neurotoxicity.