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Enhanced neuroinflammation and oxidative stress are associated with altered hippocampal neurogenesis in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated mice

Singh, Sonua,,*; Mishra, Akankshaa,,b,,*; Tiwari, Virendraa,,b; Shukla, Shubhaa,,b

doi: 10.1097/FBP.0000000000000516
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Loss of midbrain dopaminergic neurons in Parkinson’s disease not only induces motor impairments but also leads to the development of non-motor symptoms such as memory impairment, anxiety and depression. Dopaminergic axons directly innervate hippocampus and release dopamine in the local environment of hippocampus, and hence are directly involved in the modulation of hippocampal-dependent functions. Studies have explored the potential effect of dopamine on adult hippocampal neurogenesis. However, it is not well defined whether oxidative damage and inflammation could be associated with alteration in adult hippocampal neurogenesis. In the present study, we analyzed the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on adult hippocampal neurogenesis and how it is associated with inflammatory conditions in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson’s disease-like phenotypes. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice exhibited significantly reduced dopaminergic neurons and dopamine content that resulted in impairment of motor functions. Interestingly, the formation of endogenous neuronal precursor cells and the number of neuroblasts in the hippocampus were significantly increased following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. Net hippocampal neurogenesis was also reduced in the hippocampus after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. These effects in the hippocampus were associated with increased oxidative stress markers and a massive reactive gliosis. Taken together, our results suggest that degeneration of midbrain dopaminergic neurons directly affects the local hippocampal microenvironment by enhancing inflammatory influences. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced inflammatory reaction in the hippocampus may alter the endogenous regenerative capacity of the brain. Therefore, anti-inflammatory agents could be a potential therapy for the improvement of the endogenous regenerative capacity of the aging or neurodegenerative brain.

aDivision of Neuroscience and Ageing Biology, CSIR–Central Drug Research Institute, Lucknow

bAcademy of Scientific and Innovative Research, New Delhi, India

* Sonu Singh and Akanksha Mishra contributed equally to the writing of this article.

Received 15 April 2019 Accepted as revised 17 September 2019

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Correspondence to Shubha Shukla, PhD, Division of Neuroscience and Ageing Biology, CSIR–Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, Uttar Pradesh, India, E-mail: shubha_shukla@cdri.res.in

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