title: Spermidine ameliorates 3-nitropropionic acid (3-NP)-induced striatal toxicity: Possible role of oxidative stress, neuroinflammation, and neurotransmitters.
abstract: OBJECTIVE
  Spermidine, a naturally occurring polyamine, is involved in various internal biological functions, due to its antioxidant and anti-inflammatory properties. A decreased level of polyamines is associated with aging and neurodegenerative disorders including Huntington disease (HD). 3-Nitropropanoic acid (3-NP) induces a spectrum of HD-like neuropathologies in rat striatum and thus serves as a good experimental model of HD. Therefore, the aim of the present study was to investigate whether spermidine confers neuroprotection against 3-NP-induced striatal toxicity and to explore its possible mechanism.
  
  
  METHODS
  Rats were administered 3-NP (10mg/kg/day, i.p.) for 21 days. Spermidine (5 and 10mg/kg/day, p.o.) was administered once a day 1h before 3-NP treatment for 21 days. Body weight and behavioral observations were recorded at weekly intervals after continuous 3-NP treatment. On the 22nd day, the animals were sacrificed, and the rat striatum was isolated for the estimation of biochemical parameters (lipid peroxidation (LPO), glutathione (GSH), and nitrite), determination of pro-inflammatory cytokine levels (tumor necrosis factor (TNF)-α and interleukin (IL)-6 and IL-1β), and neurochemical analysis (gamma-aminobutyric acid (GABA), glutamate, dopamine (DA), norepinephrine (NE), 5-HT, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), adenosine, inosine, and hypoxanthine).
  
  
  RESULTS
  The findings of the present study demonstrate significant alterations in motor coordination, oxidative defense, and the levels of pro-inflammatory mediators (TNF-α, IL-6, and IL-1β) and striatal neurotransmitters upon 3-NP treatment. Pretreatment with spermidine significantly attenuated 3-NP-induced alterations in motor coordination, oxidative stress, and the levels of neuroinflammatory markers and striatal neurotransmitters.
  
  
  CONCLUSIONS
  Our findings suggested that spermidine exerted a potential neuroprotective effect in a 3-NP model of HD, which may provide insight into the therapeutic potential of spermidine for HD.
authors.affiliation: Neuropharmacology Division, Department of Pharmacology, I.S.F. College of Pharmacy, Moga 142001, Punjab, India; Junior Research Fellow, I. K. Gujral Punjab Technical University, Jalandhar, Punjab, India.
authors.forename: Sumit
authors.initials: S
authors.lastname: Jamwal
authors.affiliation: Neuropharmacology Division, Department of Pharmacology, I.S.F. College of Pharmacy, Moga 142001, Punjab, India. Electronic address: punnubansal79@gmail.com.
authors.forename: Puneet
authors.initials: P
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011422:Propionates / Q000633:toxicity*; D011897:Random Allocation; D017208:Rats, Wistar; D045442:Rotarod Performance Test; D013095:Spermidine / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid; D013095:Spermidine
keywords: 3-Nitropropionic acid; Catecholamines; GABA; Glutamate; Huntington's disease; Oxidative stress; Spermidine