Neurodegenerative changes in depression: Excitotoxicity or a deficit of trophic factors?

Abstract

Here we review data on the impairments of functions of the glutamatergic system in the development of depressive states in humans and animals. We discuss the key role of these impairments in mechanisms of neurodegenerative changes in depression. Two principal lines of study link atrophy of the prefrontal cortex and hippocampus with excitotoxic neuronal damage or a deficit of trophic factors. The hypothesis on the involvement of excitotoxic damage to neurons in depression is based on impaired function of glutamate transporters and massive death of astrocytes that utilize glutamate. Drugs that contain activators of glutamate transporters or inhibitors of presynaptic glutamate release are under development. In this review, we also discuss the advantages of an alternative hypothesis on deadaptation of the mechanisms of presynaptic, including structural, plasticity due to a deficit of trophic factors.