Neurocytoskeletal Protective Effect of Melatonin: Importance for Morphofunctional Neuronal Polarization

Abstract

Neurons have a highly asymmetric shape and they are constituted by two functional domains: the axonal, and the somatodendritic domains. Axons are cellular processes that make contact with target cells to transmit information, while dendrites located in the somatodendritic domain are specialized in the reception of information. During neurodevelopment, neurons acquire the highly morphofunctional polarization through a dynamic cytoskeletal organization. Melatonin, the main indolamine secreted by the pineal gland has two important properties which play a key role in the maintaining of neuron polarization: it is a potent free radical scavenger, and it is a cytoskeletal modulator. Melatonin stimulates cytoskeletal polarization through PKC and ROCK activation by recruiting cells at early stages of neurodevelopment for later differentiation. At later stages, melatonin induces neurite and microtubule enlargement by a calmodulin antagonism. Moreover, melatonin prevents the asymmetric shape lost induced by oxidative stress, a condition present in neuropsychiatric diseases, and abolishes the cytoskeletal damage caused by prolonged treatment with antipsychotics, restoring the morphofunctional polarization. Moreover, in organotypic cultures, melatonin at nanomolar concentrations enhances the number of dendrites and their complexity in hilar neurons of the hippocampus. In addition, melatonin stimulates the formation of new neurons in vitro and in a rodent model. In this review we will describe current evidences indicative of the melatonin participation in the neuronal morphofunctional differentiation as a cytoskeletal modulator. Also we will discuss the implications of the loss of neuronal polarization in neuropsychiatric diseases and the potential therapeutic utility of melatonin for the treatment of these illnesses.