P2‐164: NEUROPROTECTIVE MECHANISM OF SPERMIDINE ALONE AND IN COMBINATION WITH NITRIC OXIDE PATHWAY MODULATORS AGAINST 3‐NP‐INDUCED BEHAVIORAL, BIOCHEMICAL AND NEUROTRANSMITTER ALTERATIONS IN RAT STRIATUM

Abstract

Huntington's disease (HD) is fatal, hyperkinetic and characterized by motor and non-motor symptoms for there is no clinically available drug. Emerging strides have implicated the role of neurotransmitters alteration, excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation in HD pathophysiology. Polyamines (Spermidine) are documented to regulate mitochondria Ca2+ transport, nitric oxide synthase, neuroinflammation and oxidative stress. 3-NP induces a spectrum of HD-like neuropathology in rat striatum and widely used as experimental tool to study HD. Rats were administered with 3-NP (10 mg/kg/day, i.p.) for 3 weeks. Spermidine (5 and 10 mg/kg/day, p.o.) was given once a day, 1 hour prior to 3-NP treatment for 3 weeks. Either, L-NAME (10 mg/kg; i.p.), a nitric oxide synthase inhibitor and L-arginine (50 mg/kg; i.p.), a nitric oxide synthase precursor were administered with spermidine in respective groups. In the end of study, animals were sacrificed and striatum was isolated for various biochemical, neuroinflammation and neurotransmitters analysis. 3-NP treatment significantly changed body weight, locomotor activity, motor coordination, oxidative defense, pro-inflammatory mediators and striatal neurotransmitters level. Pre-treatment with spermidine (5 and 10 mg/kg; p.o.) alone for 21 days significantly prevented the 3-NP induced alterations. In addition, concurrent treatment of Spermidine (5 mg/kg; p.o.) with L-NAME (10 mg/kg; i.p.) significantly enhanced observed protective effect of Spermidine (5 mg/kg; p.o.) whereas concurrent treatment of Spermidine (10 mg/kg; p.o.) with L-Arg (50 mg/kg; i.p.) significantly reduced observed protective effect of Spermidine (10 mg/kg; p.o.). The observed neuroprotective efficacy of Spermidine is attributed to its anti-oxidant and anti-inflammatory properties and prevention of neurotransmitters level in striatum.