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Effects of Brain Ischemic Preconditioning on Cognitive Decline and Motor Incoordination in 3-Nitropropionic Acid-Intoxicated Rats: Probable Mechanisms of Action

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Neurophysiology Aims and scope

The paradigm of brain ischemic preconditioning (BIP) rendering protection from succeeding chemical insults has not been established in vivo. Systemic administration of 3-nitropropionic acid (3-NP) damages cerebral basal ganglia by inducing a mitochondrial dysfunction: this serves as a translational model for Huntington’s disease. We tested the potential of BIP against the neurotoxic effects of 3-NP and investigated the role of glycogen synthase kinase 3-beta (GSK-3β) and heat shock protein-72 (HSP72) signalling in the mentioned model. Male Wistar rats (n = 8; 180-200 g) were randomly assigned to seven groups, sham, BIP, 3NP, BIP+3NP, LiCl+BIP+3NP, Que (quercetin) +BIP+3NP, and LiCl+Que+BIP+3NP. Lithium chloride, 3-NP, and quercetin were administered in the doses of 40, 35, and 4 mg/kg i.p., respectively. Deficits in motor coordination and memory retention were assessed using the balance beam, accelerating rotarod, gait analysis, Morris water maze, and elevated plus maze. Brain biochemistry was assessed for the markers of lipid peroxidation and nitric oxide. The findings revealed noticeable differences in the measured indices in the examined animal groups vs. the sham group (P < 0.05 for motor coordination, memory retention, and brain biochemistry). A strong negative correlation between the rotarod performance of animals and their brain MDA levels was found. The findings reveal that BIP provides behavioral and biochemical recuperation against 3NP-induced neurodegeneration, and this is related to downregulation of GSK -3β and upregulation of HSP72.

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  1. Neuropharmacology Laboratory, School of Pharmaceutical Sciences, Shoolini University, Solan, India

    A. Sharma & R. Goyal

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Sharma, A., Goyal, R. Effects of Brain Ischemic Preconditioning on Cognitive Decline and Motor Incoordination in 3-Nitropropionic Acid-Intoxicated Rats: Probable Mechanisms of Action. Neurophysiology 51, 160–170 (2019). https://doi.org/10.1007/s11062-019-09809-5

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