Research Article  |  Published 13 March 2019

Neuroprotective effects of carnitinoid compounds in rodent cellular and in vivo models of mitochondrial complex I dysfunction

Michelle E. Hoffman1, Brett N. Augsburger1, Chad D. Foradori2, Kodeeswaran Parameshwaran3, Shannon Helsper1, Jonathan G. Marable1, Kosta Steliou4,5, Carl A. Pinkert1, and Michael H. Irwin1

1Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA. 2Department of Anatomy Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA. 3Department of Biological and Environmental Science, Texas A&M University-Commerce, Commerce, TX, USA. 4Cancer Research Center, Boston University School of Medicine, Boston, MA, USA. 5PhenoMatriX, Inc., Natick, MA, USA.

Abstract

Rotenone-mediated mitochondrial complex I inhibition was used to model Parkinson’s disease-like syndrome in Lewis rats. Tyrosine hydroxylase immunolabeling demonstrated a decrease in the number of dopaminergic neurons as well as aberrant morphology in surviving neurons. Administration of carnitinoid compounds (synthetic lipoylcarnitine or butyrylcarnitine compounds) reduced dopaminergic neuronal cell loss with characteristic morphology observed in surviving neurons. In a rat primordial hippocampal cell line (H19-7/IGF-IR), rotenone treatment resulted in increased ROS and reduced cellular ATP, while co-treatment with lipoylcarnitine maintained ROS and ATP at control levels. These results illustrate the therapeutic potential of small-molecule carnitinoids in treating neurodegenerative diseases associated with mitochondrial dysfunction.

Keywords:
Mitochondria, complex I, carnitinoids, rodent modeling, neurodegeneration, Parkinson’s disease.

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