Research Interest
Although human brain represents only ~2% of the body weight, it accounts for ~20% of total oxygen utilization of the whole body indicating the overwhelming energy demands of the brain. Glutamate and gamma-aminobutyric (GABA) acid are the major excitatory and inhibitory neurotransmitters, respectively, in the matured mammalian central nervous system. These neurotransmitters are involved in many functions such as behavior, cognition, emotion, and are shown to be affected in different neurological conditions. In vivo 13C NMR studies have shown that the rates of neurotransmitter cycle and neuronal mitochondrial glucose oxidation are stoichiometrically coupled indicating neuronal energetics is supported by oxidative glucose metabolism. My current research interest lies on the development and application of the state-of-the-art magnetic resonance spectroscopy and stable 13C isotope (glucose and acetate) techniques to study cerebral metabolism in healthy as well as in different neurological conditions such as Alzheimer's Disease, Parkinson's Disease, depression and addiction in rodent models. Metabolism of [1,6-13C2]glucose via glutamatergic and GABAergic TCA cycles label glutamate and GABA at different carbon positions. [2-13C]Acetate is selectively metabolized in astroglia and labels glutamaine-C4. Neurotransmitters glutamate and GABA are labeled via glutamate-glutamine and GABA-glutamine substrates cycling, respectively. Cerebral metabolic rates are determined by modeling of the 13C turnover of amino acids from labeled substrate. The measurements of metabolic rates provide a comprehensive assessment of excitatory and inhibitory neuronal, and astroglial function in different neurological conditions.
The major objectives of our studies are following:
Identify the atrophy in different brain regions during normal ageing and at various stage of Alzheimer's disease in mouse model.
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Determine the effects of normal ageing and Alzheimer's disease on the eneregics of glutamatergic (excitatory neuron), GABAergic neurons (inhibitory neuron) and astroglia.
Understand the role of caloric restricted diet and memory enhancing dugs in brain atrophy, cerebral metabolites and neurotransmitter energetics during normal ageing and in Alzheimer's disease.
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Develop non-invasive NMR method for studying hepatic, diabetes, etc. diseases.
Ongoing Projects
NMR Investigations of Brain Energy Metabolism during Normal Aging and in Alzheimer’s Disease :
The cognitive aging describes a pattern of mild age-related impairments in cognitive functions. Normal brain aging is associated with subtle morphological and functional alterations in specific neuronal circuits, rather than large scale loss of neurons. Alzheimer’s disease is the most common neurodegenerative disorder associated with gradual deterioration of cognitive function, personality and behavior. The cause and pathogenesis of Alzheimer’s disease remains complex. The major obbjective of the current study is to investigate the effect of normal aging and Alzheimer’s diseases on regional brain metabolites profile, neurotransmitter (glutamate, GABA) energetics in mice model.
Exploring Brain Energy Metabolism in Parkinson’s Disease in vivo using Nuclear Magnetic Resonance :
Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder of the central nervous system with impaired motor skills and speech affecting mainly elderly people. Although PD is one of the most intensively investigated neurodegenerative disorders, the cause of the nigral degeneration in PD is not yet fully understood. One of the problems in PD research is the ability to develop methods for early detection of preclinical disease. Identification of metabolic / neurochemical markers may be important for diagnosing PD before clinical symptoms appear. We are studying Parkinson’s disease in mouse model.
Exploring the Astroglial Pathology in Mood Disorders:
Major depressive disorder is a complex neuropsychiatric syndrome and often very severe and life threatening. Astroglia are not only responsible for protecting neurons from the deleterious effect of elevated neurotransmitters (Glu and GABA) level but are also the principle source of the synaptically released Glu/GABA as a key participant in the neurotransmitter cycle. We are investigating the effect of stress on regional brain metabolites profile, astroglial and neuronal metabolism and neurotransmitter cycle associated with glutamate and GABA neurotransmitters pathway in mice model using NMR spectroscopy approach.
NMR Investigation of molecular and metabolic changes associated with alcohol and nicotine addiction in developing and matured brain
Addiction is a primary chronic disease which results in a persistent use of sbustance despite negative consequences. Severe cognitive problems and psychiatric disorders are common in alcoholics. In these studies we are investigating effects of alcohol and nictotine on glutamate and GABA neurotransmitter cycle flux and glucose oxidation.
Posted on Feb 29, 2016
