[NMR paper] Parkin prevents cortical atrophy and A?-induced alterations of brain metabolism: ¹³C NMR and magnetic resonance imaging studies in AD models.

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Parkin prevents cortical atrophy and A?-induced alterations of brain metabolism: ¹³C NMR and magnetic resonance imaging studies in AD models.

Related Articles Parkin prevents cortical atrophy and A?-induced alterations of brain metabolism: ¹³C NMR and magnetic resonance imaging studies in AD models.

Neuroscience. 2012 Dec 6;225:22-34

Authors: Algarzae N, Hebron M, Miessau M, Moussa CE

Abstract
Alzheimer's disease (AD) is a neurodegenerative aging disorder characterized by extracellular A? plaques and intraneuronal neurofibrillary tangles. We conducted longitudinal studies to examine the effects of A? on brain amino acid metabolism in lentiviral A?(1-42) gene transfer animals and transgenic AD mice. We also performed lentiviral parkin gene delivery to determine the effects of A? clearance in AD models. A?(1-42) activated mTOR signaling, and increased 4E-BP phosphorylation. A?(1-42) increased the synthesis of glutamate and aspartate, but not glutamine, leucine and isoleucine, but an increase in leucine and isoleucine levels was concurrent with diminution of neurotransmitters. Additionally, A?(1-42) attenuated mitochondrial tricarboxylic acid (TCA) cycle activity and decreased synthesis of its by-products. Glutamate levels increased prior to lactate accumulation, suggesting oxidative stress. Importantly, parkin reversed the effects of A?(1-42) on amino acid levels, prevented TCA cycle impairment and protected against glutamate toxicity. Cortical atrophy was observed in aged 3xTg-AD mice, while parkin expression was associated with reduced atrophy. Similarly, A?(1-42) resulted in significant cell loss, pronounced astrogliosis and cortical atrophy and parkin reduced astrogliosis and reversed A?(1-42) effects on cell loss and cortical atrophy. Taken together these data suggest that parkin prevents amyloid-induced alteration of brain metabolism and may be used as a therapeutic target to limit neuronal loss in AD.


PMID: 22960314 [PubMed - indexed for MEDLINE]



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