BDNF increases rat brain mitochondrial respiratory coupling at complex I, but not complex II

Abstract

Brain-derived neurotrophic factor (BDNF) governs both the selective survival of neurons during development and the experience-based regulation of synaptic strength throughout life. BDNF produced a concentration-dependent increase in the respiratory control index (RCI, a measure of the efficiency of respiratory coupling, ATP synthesis and organelle integrity) of rat brain mitochondria. This effect was mediated via a MAP kinase pathway and highly specific for oxidation of glutamate plus malate (complex I) by brain mitochondria. The oxidation by brain mitochondria of the complex II substrate succinate was unaffected by BDNF. The failure of BDNF to modify respiratory activity associated with mitochondrial preparations isolated from rat liver indicates that the actions of the neurotrophin are tissue specific. BDNF also increased the RCI values associated with Ca2+ -induced respiration to a similar extent. This is the first demonstration that BDNF, in addition to modifying neuronal plasticity, can modify brain metabolism and the efficiency of oxygen utilization. The finding that neurotrophins can alter mitochondrial oxidative efficiency has important implications for neurodegenerative and psychiatric diseases.

Depression gets old fast: do stress and depression accelerate cell aging?

“…[137,139,140] A role of BDNF in antidepressant mechanisms of action is supported by findings that hippocampal neurogenesis (in animals) and serum BDNF concentrations (in depressed humans) increase with antidepressant treatment, [137,140] and that hippocampal neurogenesis is required for behavioral effects of antidepressants in animals. [141] Apart from its direct neurotrophic actions, BDNF also has antiinflammatory and antioxidant effects and improves the efficiency of brain mitochondrial oxygen utilization, which may contribute to its neuroprotective efficacy, [142,143] BDNF attenuates glucocorticoid-induced neuronal death, [144] and BDNF activity synergizes with telomerase activity (discussed below) in promoting the growth of developing neurons. [145] CELL AGING: TELOMERES AND TELOMERASE…”

Transcriptional Regulation of Brain-derived Neurotrophic Factor Coding Exon IX

“…BDNF functions at the interface of metabolism and synaptic plasticity. On the one hand, it interacts with metabolic molecules (55), influences mitochondrial energy management efficiency (56,57), and alters glucose utilization in neurons (58). On the other hand, it enhances glutamate release and increases the abundance of NMDA and AMPA receptors and their delivery to the plasma membrane, thereby up-regulating receptor activity in hippocampal and cortical neurons (59 -61).…”

Mitochondrial Functions in Mood Disorders

“…BDNF promotes synaptic plasticity, in part, by enhancing mitochondrial energy production. It increases glucose utilization and increases mitochondrial respiratory coupling at complex [62,142].…”