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Abstract #1976

Dietary Restriction Recovers Cerebral Activity in Pitx3 Knockout Mouse Model of Parkinsons Disease

Puneet Bagga1, Anup Nirmal Chugani1, M Suresh Kumar1, Anant Bahadur Patel1

1NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Pitx3 knockout (Pitx3-/-) mouse model is a well characterized genetic model of Parkinsons disease (PD) due to malformation of substantia nigra leading to loss of dopamine innervations in striatum. Dietary restriction (DR) is linked with longevity and neuroprotection via many mechanisms. Regional cerebral metabolism was monitored by infusion of [1,6-13C2]glucose for 10 min in conjunction with 1H-[13C]-NMR spectroscopy of mice brain extracts. Glucose oxidation by Glutamatergic and GABAergic neurons was decreased, additionally thalamus-hypothalamic excitatory activity and neurotransmission was found to be reduced in Pitx3-/- mice which was observed to be recovered after 6 months of DR.

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Keywords

abnormal access acids activity aging alternate amino anesthetized animals biology blood brain calorie cellular cerebral characterized chronic combination common concentration conditions conjunction control cortex cortical cycle cycling decreased dietary disease disorder dopamine drug elevated energy enrichment evaluate every exhibits experiment expression extracted extracts fasted flow folds food formation free frozen function funding genetic glucose government head human hypo improving induction infused infusion innervations intake intervention knockout labeled labeling laboratory leading linked liquid longevity loss male malformation management materials metabolic metabolism metabolites mice model molecular month months mouse neurons neurotransmitter normalization objective overnight oxidation patients potential proteins providing recover recovers reduced reported restriction returned science significantly situ spectra spectroscopy strategy stress studies subjected suggest suggesting supported technology tissue treatment type understand urethane wild