Amit Khairnar Team

Evaluating the effect of astrocyte senescence in alpha-synuclein accumulation-induced neuroinflammation and neurodegeneration in intranasal rotenone mouse model of Parkinson’s disease

The lab is mostly involved in identifying effect of enteric neuroinflammation in development and progression of alpha synuclein pathology from gut to brain. Also, the PI is involved in development of progressive mouse models of PD from olfactory bulb to mid brain. The PI was able to identify the significance of novel structural Magnetic resonance imaging called diffusion kurtosis imaging (DKI) in diagnosing the PD patients at early stage. 3 Ph.D. students already defended their Pre-PhD and submitted the thesis under the supervision of Amit Khairnar. The PI was successful in receiving the Marie Curie fellowship. He has completed many projects and has rich experience in developing progressive mouse PD models and understanding the pathology behind the development of alpha-synuclein pathology.

Accumulation of alpha-synuclein (α-syn) is central to the pathogenesis of Parkinson's disease (PD). Previous studies suggest that α-syn pathology may originate from the olfactory bulb (OB) or gut in response to an unknown pathogen and later progress to the different brain regions. Aging is viewed as the utmost threat to PD development. Therefore, studies depicting the role of age in α-syn accumulation and its progression in PD are essential. In our recent studies with 3- and 12-months old mice we observed a difference in alpha synuclein accumulation induced neuroinflammation and neurodegeneration. We did not observed alpha synuclein accumulation induced neuroinflammation and neurodegeneration after giving rotenone intranasally to 3 months old mice but in 12 months old mice. It suggests there are different age-related factors which are involved in alpha synuclein accumulation induced neurodegenerative changes. Astrocyte shown to undergo senescence with aging and it is involved in development of different neurological disorders. We are looking for a candidate whose goal will be detecting the effect of astrocyte senescence on rotenone induced alpha synuclein accumulation and neurodegeneration.

Publications:

Sharma M, Kaur J, Rakshe S, Sharma N, Khunt D, Khairnar A. (2022) “Intranasal Exposure to Low-Dose Rotenone Induced Alpha-Synuclein Accumulation and Parkinson's Like Symptoms Without Loss of Dopaminergic Neurons” Neurotox Res; 40(1): 215-229. doi: 10.1007/s12640-021-00436-9.

Sharma M, Sharma N, Khairnar A. (2022) “Intranasal Rotenone Induces Alpha-Synuclein Accumulation, Neuroinflammation and Dopaminergic Neurodegeneration in Middle-Aged Mice” Neurochem Res. doi: 10.1007/s11064-022-03847-y.

Nishant Sharma, Monika Sharma, Disha Thakkar, Hemant Kumar, Sona Smetanova, Lucie Buresova, Petr Andrla, Amit Khairnar. (2022) ”Intragastric administration of low-dose rotenone post-colitis exacerbates damage to the nigrostriatal dopaminergic system in Parkinson’s disease: The pace accelerates even more” https://www.biorxiv.org/content/10.1101/2022.12.22.521569v1 (Available as a Pre-print).

Amit Suresh Khairnar, Ph.D.

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