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Principal Investigator: Cory Justin White
Organization: EMORY UNIVERSITY
Fiscal Year: 2024
Award: $101,402
Funding agency: National Institute of Neurological Disorders and Stroke
PROJECT SUMMARY/ABSTRACT
Defects in lipid metabolism are associated with neurological diseases and mood disorders, but
bioenergetics and regulation of lipid metabolism in the brain is not well defined. The brain is the most lipid-rich
tissue in mammals other than adipose with a unique profile of lipids necessary for proper nervous system
structure and function. However, how the brain uses lipids for energy and responds to dietary conditions that
impact available lipids is grossly understudied. Historically, there has been little consideration for a) the
existence, capacity, and relevance of fatty acid oxidation (FAO) in the brain in comparison to more prominent
sources of energy such as glucose (and ketones during fasting and starvation) nor b) how the brain senses
and adapts to changes in availability of lipids. Throughout my predoctoral training, I have already determined
(Aim 1a) that the mammalian brain normally oxidizes long chain fatty acids in vivo to a greater extent than
previously considered using a pan-brain-specific conditional mouse model incapable of FAO (manuscript in re-
review in MCB) and (Aim 1b) identified that expression of ethanolamine phosphate phospholyase (Etnppl)
(funded by F31, manuscript in prep), which has links to schizophrenia and bipolar disorder in humans, is
upregulated by dietary fasting specifically in astrocytes from Ribo-Tag mice using translating ribosomal affinity
purification. The contributions of ETNPPL to the brain metabolome were evaluated using constitutive ETNPPL
knockout mice (ETNPPL-/-). Under the F99 phase, I will study (Aim 2a) how perturbations in hepatic FAO
(supplies brain ketones), using mice with FAO deletion in both brain and liver, impacts FAO bioenergetics in
brain and (Aim 2b) continue studying how the brain responds to metabolic cues by further characterizing
ETNPPL in the brain using adeno-associated virus-injected ETNPPL overexpressed mice. In preparation for
postdoctoral studies, I will expand my knowledge in neuro-HIV in a neuro-HIV seminar series, neuro-HIV
course, and other didactic training opportunities offered at Johns Hopkins in the F99 phase. Aims 1 was and
Aim 2 will be conducted in the laboratory of Michael Wolfgang, Ph.D. at Johns Hopkins School of Medicine
during my graduate studies in the Biochemistry, Cellular and Molecular Biology Ph.D. Program. For the K00
phase, (Aim 3) I am pursuing postdoctoral training that will expand my current knowledge in lipid
neurometabolism in the context of an infectious disease with neuropathological manifestations. I have a
particular interest in the impact on brain lipid metabolism by HIV infection. This interest is based on high
indices of cognitive impairment and dementia in HIV infected patients (collectively known as HAND), the brain
being a reservoir for HIV, and antiretroviral drugs used long-term to treat HIV having metabolic side-effects. In
summary, these training opportunities afforded by the support of the D-SPAN award would be immensely
impactful towards my development into an innovative, independent researcher studying the intersection of
neuroscience, metabolism, and infectious disease.
Terms: <AIDS Virus><ASD><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Address><Adeno-Associated Viruses><Adipose tissue><Affective Disorders><Affinity Chromatography><Amentia><Anti-Retroviral Agents><Assay><Astrocytes><Astrocytus><Astroglia><Autism><Autistic Disorder><Autopsy><Autoregulation><Award><Bioassay><Biochemistry and Cellular Biology><Bioenergetics><Biological Assay><Bipolar Affective Psychosis><Bipolar Disorder><Body Tissues><Brain><Brain Nervous System><CNS Nervous System><CPT 1><Carbohydrates><Carnitine Acyltransferase I><Carnitine O-Palmitoyltransferase><Carnitine Palmitoyltransferase><Carnitine Palmitoyltransferase I><Central Nervous System><Cephalins><Cognition><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Communicable Diseases><Cues><D-Glucose><DNA Molecular Biology><Defect><Dementia><Dependoparvovirus><Dependovirus><Development><Dextrose><Diet><Disease><Disorder><Disturbance in cognition><Doctor of Philosophy><Drug usage><Early Infantile Autism><Encephalon><Energy-Generating Resources><Enzyme Gene><Enzymes><Epilepsy><Epileptic Seizures><Epileptics><Ethanolamine Phosphoglycerides><Ethanolamineglycerophospholipids><Fasting><Fats><Fatty Acid Metabolism Pathway><Fatty Acids><Fatty Tissue><Fatty acid glycerol esters><Fellowship><Funding><Future><Gene Transcription><Genes><Genetic><Genetic Transcription><Glucose><Goals><HIV><HIV 1 associated neurocognitive disorder><HIV Infections><HIV associated neurocognitive deficit><HIV associated neurocognitive impairment><HIV associated neurological disease><HIV associated neurological disorder><HIV induced neurocognitive deficit><HIV induced neurocognitive impairment><HIV neurocognitive impairment><HIV-1 associated neurocognitive deficit><HIV-1 associated neurocognitive disorder><HIV-1 associated neurocognitive impairment><HIV-associated neurocognitive disorder><HTLV-III Infections><HTLV-III-LAV Infections><Hepatic><Homeostasis><Human><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><Impaired cognition><Impairment><Incidence><Infantile Autism><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Intermediary Metabolism><Intervention><Intervention Strategies><Investigators><KO mice><Kanner's Syndrome><Ketone Bodies><Ketones><Knock-out><Knock-out Mice><Knockout><Knockout Mice><Knowledge><LAV-HTLV-III><Laboratories><Link><Lipids><Liver><Lymphadenopathy-Associated Virus><MALD-MS><MALDI><MALDI-MS><Mammalia><Mammals><Manic-Depressive Psychosis><Manuscripts><Membrane><Mental Depression><Mentors><Metabolic><Metabolic Processes><Metabolism><Mice><Mice Mammals><Modern Man><Molecular Biology><Mood Disorders><Murine><Mus><NRSA><National Research Service Awards><Nervous System><Nervous System Diseases><Nervous System Disorder><Nervous System Physiology><Neuraxis><Neurocognitive Impairment in HIV><Neurocognitive Impairment in HIV-1><Neurologic><Neurologic Body System><Neurologic Disorders><Neurologic Organ System><Neurologic function><Neurological><Neurological Disorders><Neurological function><Neurosciences><Null Mouse><O-(1-beta-acyl-2-acyl-sn-glycero-3-phospho)-ethanolamine><Palmitoylcarnitine Transferase><Palmitylcarnitine Acyltransferase><Patients><Peripheral><Persons><Ph.D.><PhD><Phase><Phosphatides><Phosphatidylethanolamine><Phospholipids><Physiological Homeostasis><Postdoc><Postdoctoral Fellow><Predisposition><Preparation><RNA Expression><Radiolabeled><Regulation><Research><Research Associate><Research Personnel><Researchers><RiboTag><Ribosomes><Role><Schizophrenia><Schizophrenic Disorders><Seizure Disorder><Series><Source><Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization><Spectroscopy, Mass, Matrix-Assisted Laser Desorption-Ionization><Starvation><Structure><Susceptibility><Therapeutic><Tissues><Training><Transcription><Translating><Virus-HIV><Work><acylcarnitine><adeno associated virus group><adipose><affinity purification><anti-retroviral><antiretroviral therapy><antiretroviral treatment><astrocytic glia><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><bipolar affective disorder><bipolar disease><bipolar illness><bipolar mood disorder><brain metabolism><career><carnitine palmitoyltransferase 1><cognitive dysfunction><cognitive loss><conditional knock-out><conditional knockout><dementia praecox><depression><developmental><dietary><diets><drug use><energy source><epilepsia><epileptogenic><ethanolamine phosphate><experiment><experimental research><experimental study><experiments><fasted><fasts><fat metabolism><fatty acid metabolism><fatty acid oxidation><hepatic body system><hepatic organ system><imaging mass spectrometry><in vivo><indexing><innovate><innovation><innovative><interest><interventional strategy><ketogenic><ketogentic><lipid metabolism><long chain fatty acid><manic depressive disorder><manic depressive illness><mass spectrometric imaging><matrix assisted laser desorption ionization><medical college><medical schools><membrane structure><metabolic profile><metabolism measurement><metabolome><metabolomics><metabonome><metabonomics><mouse model><murine model><necropsy><nervous system function><neuro-AIDS><neuro-HIV><neuroAIDS><neuroHIV><neurological disease><neuropathologic><neuropathological><neuropathology><overexpress><overexpression><oxidation><phosphoethanolamine><phosphorylethanolamine><post-doc><post-doctoral><post-doctoral trainee><post-doctoral training><postdoctoral training><postmortem><pre-doc><pre-doctoral><predoctoral><preparations><programs><radiolabeling><radiologically labeled><research associates><response><schizophrenic><school of medicine><side effect><skill acquisition><skill development><skills><social role><tool><training opportunity><white adipose tissue><yellow adipose tissue>