5-N-ethyl Carboxamidoadenosine Stimulates Adenosine-2b Receptor-Mediated Mitogen-Activated Protein Kinase Pathway to Imp
- PDF / 2,487,548 Bytes
- 15 Pages / 595.276 x 790.866 pts Page_size
- 9 Downloads / 161 Views
ORIGINAL PAPER
5‑N‑ethyl Carboxamidoadenosine Stimulates Adenosine‑2b Receptor‑Mediated Mitogen‑Activated Protein Kinase Pathway to Improve Brain Mitochondrial Function in Amyloid Beta‑Induced Cognitive Deficit Mice Bhupesh Chandra Semwal1 · Debapriya Garabadu1 Received: 23 April 2020 / Accepted: 3 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with loss in memory as one of the cardinal features. 5-N-ethyl carboxamidoadenosine (NECA), an agonist of adenosine-2b receptor, exerts neuroprotective activity against several experimental conditions. Further, NECA activates mitogen-activated protein kinase (MAPK) and also attenuates mitochondrial toxicity in mammalian tissues other than brain. Moreover, there is no report on the role of A2b/MAPK-mediated signaling pathway in Aβ-induced mitochondrial toxicity in the brain of the experimental animals. Therefore, the present study evaluated the neuroprotective activity of NECA with or without MAPK inhibitor against Aβ-induced cognitive deficit and mitochondrial toxicity in the experimental rodents. Further, the effect of NECA with or without MAPK inhibitor was evaluated on Aβ-induced mitochondrial toxicity in the memory-sensitive mice brain regions. Intracerebroventricular (ICV) injection of Aβ 1–42 was injected to healthy male mice through Hamilton syringe via polyethylene tube to induce AD-like behavioral manifestations. NECA attenuated Aβ-induced cognitive impairments in the rodents. In addition, NECA ameliorated Aβ-induced Aβ accumulation and cholinergic dysfunction in the selected memory-sensitive mouse HIP, PFC, and AMY. Further, NECA significantly attenuated Aβ-induced mitochondrial toxicity in terms of decrease in the mitochondrial function, integrity, and bioenergetics in the brain regions of these animals. However, MAPKI diminished the therapeutic effects of NECA on behavioral, biochemical, and molecular observations in AD-like animals. Therefore, it can be speculated that NECA exhibits neuroprotective activity perhaps through MAPK activation in AD-like rodents. Moreover, A2b-mediated MAPK activation could be a promising target in the management of AD. Keywords Amyloid beta · Adenosine · Memory · Mitochondria · Mitogen-activated protein kinase (MAPK) · Apoptosis
Introduction Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with clinical manifestation of loss in cognitive function and memory in an individual. It is reported that approximately 36 million people are affected with AD throughout the world (Patients 2019). The established pathophysiology of AD are the deposition of senile plaques mainly composed of amyloid beta-protein (Aβ), formation of neurofibrillary tangles and degeneration of neurons (Šimić et al. 2016), * Debapriya Garabadu [email protected]; [email protected] 1
Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura 281 406, India
decrease in the level of c
Data Loading...
