Pharmacological Modulation of TRPM2 Channels via TRPM2 Pathway Leads to Neuroprotection in MPTP-induced Parkinson’s Disease in Sprague Dawley Rats Article Swipe
Bhupesh Vaidya
,
Harpinder Kaur
,
Pavan Thapak
,
Shyam Sunder Sharma
,
Jitendra Singh
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-874639/v1
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-874639/v1
Transient receptor potential melastatin-2 (TRPM2) channels are cation channels activated by oxidative stress and adenosine di-phosphate ribose (ADPR ) . Role of TRPM2 channels has been postulated in several neurological disorders, but, it has not been explored in animal models of Parkinson’s disease (PD). Thus, the role of TRPM2 and its associated poly (ADP-ribose) polymerase (PARP) signalling pathways were investigated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model using TRPM2 inhibitor, 2-aminoethyl diphenyl borinate (2-APB) and PARP inhibitor, N-(6-Oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino) acetamide hydrochloride (PJ-34). PD was induced by using a bilateral intranigral administration of MPTP in Sprague-Dawley rats, and different parameters were evaluated. An increase in the oxidative stress was observed, leading to the locomotor and cognitive deficits in the PD rats. PD rats also showed an increased TRPM2 expression in striatum and mid brain accompanied by reduced expression of tyrosine-hydroxylase (TH) in comparison to sham animals. Intraperitoneal administration of 2-aminoethyl diphenyl borinate (2-APB) and N-(6-Oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino) acetamide hydrochloride (PJ-34) led to an improvement in the locomotor and cognitive deficits in comparison to MPTP-induced PD rats. These improvements were accompanied by a reduction in the levels of oxidative stress and an increase in TH levels in striatum and mid brain. In addition, these pharmacological interventions also led to a decrease in the expression of TRPM2 in PD in striatum and mid brain. Our results provide a rationale for the development of potent pharmacological agents targeting TRPM2-PARP pathway to provide therapeutic benefits for the treatment of neurological disease like PD.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-874639/v1
- https://www.researchsquare.com/article/rs-874639/latest.pdf
- OA Status
- green
- References
- 58
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3199375979
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3199375979Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.21203/rs.3.rs-874639/v1Digital Object Identifier
- Title
-
Pharmacological Modulation of TRPM2 Channels via TRPM2 Pathway Leads to Neuroprotection in MPTP-induced Parkinson’s Disease in Sprague Dawley RatsWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-09-09Full publication date if available
- Authors
-
Bhupesh Vaidya, Harpinder Kaur, Pavan Thapak, Shyam Sunder Sharma, Jitendra SinghList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-874639/v1Publisher landing page
- PDF URL
-
https://www.researchsquare.com/article/rs-874639/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.researchsquare.com/article/rs-874639/latest.pdfDirect OA link when available
- Concepts
-
TRPM2, Neuroprotection, MPTP, Parkinson's disease, Neuroscience, Modulation (music), Disease, Pharmacology, Chemistry, Medicine, Biology, Biochemistry, Internal medicine, Transient receptor potential channel, Physics, Receptor, AcousticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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58Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.TH | 190 |
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| abstract_inverted_index.was | 83, 107 |
| abstract_inverted_index.(TH) | 139 |
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| abstract_inverted_index.(PD). | 44 |
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| abstract_inverted_index.brain | 132 |
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| abstract_inverted_index.using | 68, 86 |
| abstract_inverted_index.(PARP) | 56 |
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| abstract_inverted_index.brain. | 196, 218 |
| abstract_inverted_index.cation | 8 |
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| abstract_inverted_index.(2-APB) | 74, 151 |
| abstract_inverted_index.(PJ-34) | 156 |
| abstract_inverted_index.(TRPM2) | 5 |
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| abstract_inverted_index.induced | 84 |
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| abstract_inverted_index.Intraperitoneal | 145 |
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| abstract_inverted_index.N-(6-Oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino) | 78, 153 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5036437604 |
| countries_distinct_count | 0 |
| institutions_distinct_count | 5 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
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| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.10469204 |
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| citation_normalized_percentile.is_in_top_10_percent | False |