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. 2025 Apr;62(4):5333-5346.
doi: 10.1007/s12035-024-04611-9. Epub 2024 Nov 14.

Deletion of the Transient Receptor Potential Melastatin 2 Gene Mitigates the 6-Hydroxydopamine-Induced Parkinson's Disease-Like Pathology

Ana Flavia F Ferreira  1   2 , Henning Ulrich  3 , Yasuo Mori  4 , Zhong-Ping Feng  5 , Hong-Shuo Sun  5   6 , Luiz Roberto Britto  7
Affiliations

Deletion of the Transient Receptor Potential Melastatin 2 Gene Mitigates the 6-Hydroxydopamine-Induced Parkinson's Disease-Like Pathology

Ana Flavia F Ferreira et al. Mol Neurobiol. 2025 Apr.

Abstract

Pharmacological inhibition of the transient receptor potential melastatin 2 (TRPM2), an oxidative stress-activated calcium channel, was previously reported to be protective in Parkinson's disease (PD). However, the inhibitors used were not TRPM2 specific, so the involvement of this channel in PD remains unclear. Here, for the first time, Trpm2 partial (+ / -) and complete (- / -) knockout mice underwent stereotaxic surgery for PD induction. Six-hydroxydopamine was injected in the right striatum. On days 3 and 6, motor behavior tests (cylinder, apomorphine, and pole test) were performed. On day 7, brains were collected for dopaminergic neuron immunostaining. Our results showed that Trpm2 + / - male and female mice had reduced motor impairment and dopaminergic neuron death after PD induction. In addition, Trpm2 - / - male and female mice showed absent or lesser motor deficit and the dopaminergic neuronal loss was no longer observed. These findings suggest that TRPM2 is involved in the PD-like pathology and that targeting TRPM2 may possibly represent a potential neuroprotective strategy for PD.

Keywords: 6-Hydroxidopamine; Gene knockout; Ion channel; Male and female mice; Neuroprotection; Transient receptor potential melastatin 2.

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Conflict of interest statement

Declarations. Animal Ethics: All animal experiments were approved by the Ethics Committee for Animal Research of the Institute of Biomedical Sciences of the University of São Paulo (CEUA-ICB/USP, Brazil, protocol number: 8395080450). Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests.

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