Changes in mitochondrial function are pivotal in neurodegenerative and psychiatric disorders: How important is BDNF?

Abstract

The brain is at the very limit of its energy supply and has evolved specific means of adapting function to energy supply, of which mitochondria form a crucial link. Neurotrophic and inflammatory processes may not only have opposite effects on neuroplasticity, but also involve opposite effects on mitochondrial oxidative phosphorylation and glycolytic processes, respectively, modulated by stress and glucocorticoids, which also have marked effects on mood. Neurodegenerative processes show marked disorders in oxidative metabolism in key brain areas, sometimes decades before symptoms appear (Parkinson's and Alzheimer's diseases). We argue that brain-derived neurotrophic factor couples activity to changes in respiratory efficiency and these effects may be opposed by inflammatory cytokines, a key factor in neurodegenerative processes.

Aging and the genetic road towards the positivity effect in memory

“…Brain mitochondrial functioning plays a crucial role in neural plasticity and cognition (e.g., see Cheng et al, 2010, for a review) and is fundamental to many neural activities whereas mitochondrial dysfunctions occur in a variety of diseases, including psychiatric and neurodegenerative disorders (e.g., Markham et al, 2014). Recently, researchers have identified a new gene polymorphism as specifically involved in mitochondrial functioning.…”

The effect of chronic tianeptine administration on the brain mitochondria: direct links with an animal model of depression

“…Recently, another interesting theory called “the mitochondrial dysfunction hypothesis” has been highlighted [1, 2]. Impaired function of mitochondria leads to bioenergetic malfunctions, diminished adenosine triphosphate (ATP) production, impaired calcium homeostasis, and the enhanced production of free radicals and oxidative stress, leading to the initiation of apoptotic processes [3].…”

“…Some data also suggested the interaction of mitochondrial function with epigenetic processes that are important in the pathogenesis of neuropsychiatric disorders, including depression symptoms [5]. All of these observations indicate that mitochondrial malfunctions may be a crucial factor in metabolic disturbances leading to depression [2]. …”

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).…”