Dépression et neuroplasticité.

peer reviewe

Dépression et neuroplasticité : des découvertes neuroanatomiques aux nouvelles stratégies thérapeutiques.

peer reviewedThe antidepressants action cannot be understood only by the neurochemical approach and the monoaminergic theory. In particular, that model does not explain the time lag between the acute chemical modulations induced by the antidepressants and the delayed clinical response. Many hypothesis have been developped to specify the antidepressants action, each of them implicating different mechanisms of receptors regulation. In the same way, the advanced knowledge in neuroanatomy leads towards the existence of specifical lesions in this pathology. Indeed, there is, in depression, a neuronal loss focused on some regions forming the cortico-striato-pallido-limbic-thalamic tract. These anatomical changes are reduced after antidepressant treatment. Accordingly, in the last decade, a new pathophysiological concept of affective disorders has emerged. This concept integrates preferentially molecular and cellular antidepressants-induced changes leading to rehabilitation of synaptic activity and neuronal trophism. In this article, we synthesize the current knowledge about the anatomical abnormalities observed in depression, and about the pathophysiological mechanisms that account for these ones. The central phenomenon in neuroplasticity turns around neurogenesis. This process takes place in the dentelate gyrus of hippocampus, where promoter cells enter in division, differentiate and become able to migrate to specifical regions of the central nervous system and to integrate into it. Neurogenesis is stimulated by neurotrophic factors, including the BDNF (brain derived neurotrophic factor) and by a lot of environmental situations. An inhibition of neurogenesis is attributed to the excess of glucocorticoids seen in stress situations like depression. Moreover, the neuronal loss in major depression is also caused by an excessive concentration of glutamate in synapsis that can lead cells to apoptotic process. Recently, it has been demonstrated that the clinical effects of the antidepressants are correlated to an elevation of neurogenesis in the dentelate gyrus. In this article, we finally present some potentially therapeutic straregies actually being studied, being aware that neuroplasticity is still a new concept (if the anxio-depressive pathology is considered) and that it thus must be seen with that reserve