Nobiletin restores impaired hippocampal mitochondrial bioenergetics in hypothyroidism through activation of matrix substrate-level phosphorylation.
Nutr Neurosci. 2014 Mar 17. Epub 2014 Mar 17. PMID: 24627959
Objective Evaluation of the effect of citrus flavonoid - nobiletin on the bioenergetics of synaptic and non-synaptic mitochondria in the hippocampus of hypothyroid rats. Methods Male Wistar rats were divided into hypothyroid (methimazole-treated), nobiletin supplemented hypothyroid, thyroxine-treated hypothyroid, and euthyroid (control) groups. Synaptic and non-synaptic (cell) mitochondria were isolated from hippocampus. Oligomycin-sensitive, oligomycin-insensitive,α-ketoglutarate dehydrogenase-dependent synthesis of adenosine triphosphate (ATP), succinate dehydrogenase, and hexokinase activities were determined luminometrically and spectrophotometrically, respectively. Results Decreased synthesis of oligomycin-sensitive and oligomycin-insensitive ATP in hypothyroid rat hippocampus was observed in synaptic and non-synaptic mitochondria. Supplementation of hypothyroid rats with nobiletin increases oligomycin-insensitive and α-ketoglutarate-dependent production of ATP in both types of mitochondria. The activity of succinate dehydrogenase in non-synapticmitochondria and the activities of hexokinase in both types of mitochondria were normalized in nobiletin-treated hypothyroid rats. Discussion Nobiletin restores reduced mitochondrial metabolism in hypothyroid rat hippocampus through acceleration of matrix substrate-level phosphorylation that may beimportant for the prevention of hypometabolic complications in neurological disorders.