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

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A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain. / Lauritzen, Knut H.; Hasan-Olive, Md Mahdi; Regnell, Christine E.; Kleppa, Liv; Scheibye-Knudsen, Morten; Gjedde, Albert; Klungland, Arne; Bohr, Vilhelm A.; Storm-Mathisen, Jon; Bergersen, Linda H.

In: Neurobiology of Aging, Vol. 48, 12.2016, p. 34-47.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Lauritzen, KH, Hasan-Olive, MM, Regnell, CE, Kleppa, L, Scheibye-Knudsen, M, Gjedde, A, Klungland, A, Bohr, VA, Storm-Mathisen, J & Bergersen, LH 2016, 'A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain', Neurobiology of Aging, vol. 48, pp. 34-47. https://doi.org/10.1016/j.neurobiolaging.2016.08.005

APA

Lauritzen, K. H., Hasan-Olive, M. M., Regnell, C. E., Kleppa, L., Scheibye-Knudsen, M., Gjedde, A., ... Bergersen, L. H. (2016). A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain. Neurobiology of Aging, 48, 34-47. https://doi.org/10.1016/j.neurobiolaging.2016.08.005

Vancouver

Lauritzen KH, Hasan-Olive MM, Regnell CE, Kleppa L, Scheibye-Knudsen M, Gjedde A et al. A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain. Neurobiology of Aging. 2016 Dec;48:34-47. https://doi.org/10.1016/j.neurobiolaging.2016.08.005

Author

Lauritzen, Knut H. ; Hasan-Olive, Md Mahdi ; Regnell, Christine E. ; Kleppa, Liv ; Scheibye-Knudsen, Morten ; Gjedde, Albert ; Klungland, Arne ; Bohr, Vilhelm A. ; Storm-Mathisen, Jon ; Bergersen, Linda H. / A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain. In: Neurobiology of Aging. 2016 ; Vol. 48. pp. 34-47.

Bibtex

@article{9645559cac644228bd3eecccf94a25f6,
title = "A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain",
abstract = "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.",
keywords = "MtDNA damage, Ketogenic diet, Biogenesis, Neurodegeneration",
author = "Lauritzen, {Knut H.} and Hasan-Olive, {Md Mahdi} and Regnell, {Christine E.} and Liv Kleppa and Morten Scheibye-Knudsen and Albert Gjedde and Arne Klungland and Bohr, {Vilhelm A.} and Jon Storm-Mathisen and Bergersen, {Linda H.}",
year = "2016",
month = "12",
doi = "10.1016/j.neurobiolaging.2016.08.005",
language = "English",
volume = "48",
pages = "34--47",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain

AU - Lauritzen, Knut H.

AU - Hasan-Olive, Md Mahdi

AU - Regnell, Christine E.

AU - Kleppa, Liv

AU - Scheibye-Knudsen, Morten

AU - Gjedde, Albert

AU - Klungland, Arne

AU - Bohr, Vilhelm A.

AU - Storm-Mathisen, Jon

AU - Bergersen, Linda H.

PY - 2016/12

Y1 - 2016/12

N2 - 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.

AB - 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.

KW - MtDNA damage

KW - Ketogenic diet

KW - Biogenesis

KW - Neurodegeneration

U2 - 10.1016/j.neurobiolaging.2016.08.005

DO - 10.1016/j.neurobiolaging.2016.08.005

M3 - Journal article

VL - 48

SP - 34

EP - 47

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -

ID: 169441538