Brain metabolism modulates neuronal excitability in a mouse model of pyruvate dehydrogenase deficiency

Author:

Jakkamsetti Vikram12ORCID,Marin-Valencia Isaac123,Ma Qian12ORCID,Good Levi B.12ORCID,Terrill Tyler12,Rajasekaran Karthik12,Pichumani Kumar4,Khemtong Chalermchai45ORCID,Hooshyar M. Ali6,Sundarrajan Chandrasekhar12ORCID,Patel Mulchand S.7,Bachoo Robert M.28,Malloy Craig R.458,Pascual Juan M.1291011ORCID

Affiliation:

1. Rare Brain Disorders Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

2. Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

3. Laboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10065, USA.

4. Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

5. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

6. Department of Mathematical Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.

7. Department of Biochemistry, SUNY Buffalo, Buffalo, NY 14203, USA.

8. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

9. Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

10. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

11. Eugene McDermott Center for Human Growth & Development / Center for Human Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract

Decreased metabolic flux due to deficient mitochondrial pyruvate dehydrogenase causes excitability dysfunction that can be modulated by acetate.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Neurological Disorders and Stroke

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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