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Journal of Cerebral Blood Flow MGAT2 Inhibitor supplier metabolism (2014) 34, 90614 2014 ISCBFM All rights reserved SSTR3 Activator Gene ID 0271-678X/14 32.00 jcbfmORIGINAL ARTICLENeuronal and astrocytic metabolism in a transgenic rat model of Alzheimer’s diseaseLinn Hege Nilsen1, Menno P Witter2 and Ursula Sonnewald1 Regional hypometabolism of glucose within the brain can be a hallmark of Alzheimer’s illness (AD). Nevertheless, small is identified in regards to the certain alterations of neuronal and astrocytic metabolism involved in homeostasis of glutamate and GABA in AD. Right here, we investigated the effects of amyloid b (Ab) pathology on neuronal and astrocytic metabolism and glial-neuronal interactions in amino acid neurotransmitter homeostasis inside the transgenic McGill-R-Thy1-APP rat model of AD compared with wholesome controls at age 15 months. Rats have been injected with [1-13C]glucose and [1,2-13C]acetate, and extracts in the hippocampal formation at the same time as a number of cortical regions have been analyzed utilizing 1H- and 13C nuclear magnetic resonance spectroscopy and high-performance liquid chromatography. Decreased tricarboxylic acid cycle turnover was evident for glutamatergic and GABAergic neurons in hippocampal formation and frontal cortex, and for astrocytes in frontal cortex. Pyruvate carboxylation, that is important for de novo synthesis of amino acids, was decreased and affected the amount of glutamine in hippocampal formation and those of glutamate, glutamine, GABA, and aspartate inside the retrosplenial/cingulate cortex. Metabolic alterations have been also detected inside the entorhinal cortex. All round, perturbations in energy- and neurotransmitter homeostasis, mitochondrial astrocytic and neuronal metabolism, and aspects on the glutamate lutamine cycle have been located in McGill-R-Thy1-APP rats. Journal of Cerebral Blood Flow Metabolism (2014) 34, 90614; doi:ten.1038/jcbfm.2014.37; published on the internet 5 March 2014 Keyword phrases: dementia; GABA; glutamate; neurotransmitters; MR spectroscopyINTRODUCTION Regional hypometabolism of glucose inside the brain can be a hallmark of Alzheimer’s illness (AD). Compromised mitochondrial function and bioenergetics in AD have also been reported, and among the most robust findings are diminished activity of quite a few enzymes involved in oxidative metabolism of glucose: the pyruvate dehydrogenase (PDH) complicated,1,2 the a-ketoglutarate dehydrogenase complex,1,2 and cytochrome c oxidase/complex IV on the electron transport chain.3 Since the tricarboxylic acid (TCA) cycle intermediate a-ketoglutarate (a-KG) would be the precursor for glutamate and subsequently for GABA in GABAergic neurons and glutamine in astrocytes, the metabolism of glucose and amino-acid neurotransmitters inside the brain is closely linked. The homeostasis of glutamate and GABA also demands glial euronal interactions, since the transporters and enzymes involved in uptake, synthesis, and degradation of those neurotransmitters are differentially distributed in neurons and astrocytes. As a result, illnesses that encompass modifications to glucose metabolism may perhaps involve alterations in cellular energy metabolism, amino-acid neurotransmitter homeostasis, and glial euronal interactions. Certainly, lowered brain glutamate levels in individuals with AD point toward impairment of neurotransmitter homeostasis within the illness.four Outcomes from 13C nuclear magnetic resonance (NMR) spectroscopy research in AD sufferers and in brain extracts from APP-PS1 mice have shown decreased oxidative metabolism of g.
