Synaptic and non-synaptic mitochondria in hippocampus of adult rats differ in their sensitivity to hypothyroidism.
Hypothyroidism in humans provokes various neuropsychiatric disorders, movement, and cognitive abnormalities that may greatly depend on the mitochondrial energy metabolism. Brain cells contain at least two major populations of mitochondria that include the non-synaptic mitochondria, which originate from neuronal and glial cell bodies (CM), and the synaptic (SM) mitochondria, which primarily originate from the nerve terminals. Several parameters of oxidative stress and other parameters in SM and CM fractions of hippocampus of adult rats were compared among euthyroid (control), hypothyroid (methimazol-treated), and thyroxine (T4)-treated hypothyroid states. nNOS translocation to CM was observed with concomitant increase of mtNOS's activity in hypothyroid rats. In parallel, oxidation of cytochrome c oxidase and production of peroxides with substrates of complex I (glutamate + malate) were enhanced in CM, whereas the activity of aconitase and mitochondrial membrane potential (ΔΨm) were decreased. Furthermore, the elevation of mitochondrial hexokinase activity in CM was also found. No differences in these parameters between control and hypothyroid animals were observed in SM. However, in contrast to CM, hypothyroidism increases the level of pro-apoptotic K-Ras and Bad in SM. Our results suggest that hypothyroidism induces moderate and reversible oxidative/nitrosative stress in hippocampal CM, leading to the compensatory elevation of hexokinase activity and aerobic glycolysis. Such adaptive activation in glycolytic metabolism does not occur in SM, suggesting that synaptic mitochondria differ in their sensitivity to the energetic disturbance in hypothyroid conditions.
I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia.
E
E
Zhuravliova
T
T
Barbakadze
N
N
Jojua
E
E
Zaalishvili
L
L
Shanshiashvili
N
N
Natsvlishvili
I
I
Kalandadze
N
N
Narmania
I
I
Chogovadze
D
D
Mikeladze
D000367:Age Factors; D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism*