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- Title
Improvement of Mitochondrial Function by Paliperidone Attenuates Quinolinic Acid-Induced Behavioural and Neurochemical Alterations in Rats: Implications in Huntington's Disease.
- Authors
Mishra, Jitendriya; Kumar, Anil
- Abstract
Quinolinic acid (QA)-induced neurotoxicity involves a cascade of events such as increased calcium concentration in cytoplasm, exhaustive ATP depletion, oxidative stress, as well as selective GABAergic, dopaminergic, and cholinergic neuronal death. Clinical data hint towards the connection between signalling of dopaminergic system and efficient amelioration of chorea following a tetrabenazine administration in Huntington's disease patients. Therefore, the present study has been designed to explore the neuroprotective potential of paliperidone, an active metabolite of risperidone (a dopaminergic antagonist) against QA-induced neurotoxicity and related complications in rats. QA (200 nmol) was administered bilaterally to the striatum over a period of 2 min by means of a 28-gauge stainless steel needle attached to a Hamilton syringe. The study protocol involves seven treatment groups ( n = 12): naïve, sham, control (QA), paliperidone (0.5, 1 and 2 mg/kg) and paliperidone (2) per se. Single bilateral intrastriatal injection of QA (200 nmol/2 μl saline) significantly caused motor incordination, memory impairment, oxidative damage, decrease in biogenic amines levels, cellular alterations (TNF-α, IL-6, PGE2, PGF2α, caspase-3, BDNF, mitochondrial function) and damage of striatal neurons compared to the sham treatment. Treatment with paliperidone (0.5, 1 and 2 mg/kg) for 21 days significantly attenuated the QA-induced behavioural (motor and memory function), neurochemical (antioxidant enzymes and biogenic amines) and cellular alterations, as well as striatal neurodegeneration. The study indicated that modulation of dopaminergic pathway by paliperidone treatment could be a useful approach in the management of motor and memory abnormality in HD patients.
- Subjects
HUNTINGTON disease; HUNTINGTON'S chorea treatment; MITOCHONDRIAL physiology; QUINOLINIC acid; NEUROCHEMISTRY; NEUROTOXICOLOGY; CATECHOLAMINES; LABORATORY rats; PATIENTS; THERAPEUTICS
- Publication
Neurotoxicity Research, 2014, Vol 26, Issue 4, p363
- ISSN
1029-8428
- Publication type
Article
- DOI
10.1007/s12640-014-9469-9