• A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain.

A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain.

Neurobiology of aging (2016-09-18)
Knut H Lauritzen, Md Mahdi Hasan-Olive, Christine E Regnell, Liv Kleppa, Morten Scheibye-Knudsen, Albert Gjedde, Arne Klungland, Vilhelm A Bohr, Jon Storm-Mathisen, Linda H Bergersen

Mitochondrial genome maintenance plays a central role in preserving brain health. We previously demonstrated accumulation of mitochondrial DNA damage and severe neurodegeneration in transgenic mice inducibly expressing a mutated mitochondrial DNA repair enzyme (mutUNG1) selectively in forebrain neurons. Here, we examine whether severe neurodegeneration in mutUNG1-expressing mice could be rescued by feeding the mice a ketogenic diet, which is known to have beneficial effects in several neurological disorders. The diet increased the levels of superoxide dismutase 2, and mitochondrial mass, enzymes, and regulators such as SIRT1 and FIS1, and appeared to downregulate N-methyl-D-aspartic acid (NMDA) receptor subunits NR2A/B and upregulate γ-aminobutyric acid A (GABAA) receptor subunits α1. However, unexpectedly, the ketogenic diet aggravated neurodegeneration and mitochondrial deterioration. Electron microscopy showed structurally impaired mitochondria accumulating in neuronal perikarya. We propose that aggravation is caused by increased mitochondrial biogenesis of generally dysfunctional mitochondria. This study thereby questions the dogma that a ketogenic diet is unambiguously beneficial in mitochondrial disorders.

Product Number
Product Description

Monoclonal Anti-Glial Fibrillary Acidic Protein (GFAP) antibody produced in mouse, clone G-A-5, ascites fluid
Anti-Mouse IgG (whole molecule)–Peroxidase antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Anti-FIS1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Anti-SIRT1 antibody produced in rabbit, affinity isolated antibody
Anti-Microtubule-Associated Protein 2 (MAP2) Antibody, Chemicon®, from rabbit
Anti-Glutamate Receptor 2 & 3 Antibody, Chemicon®, from rabbit
Anti-Actin Antibody, clone C4, clone C4, Chemicon®, from mouse
Anti-Glutamate receptor 1 Antibody, from rabbit, purified by affinity chromatography