Melatonin increases dendritogenesis in the hilus of hippocampal organotypic cultures

J Pineal Res. 2012 May;52(4):427-36. doi: 10.1111/j.1600-079X.2011.00957.x. Epub 2012 Jan 19.


Neuropsychiatric disorders are characterized by hippocampus decreased volume and loss of dendrite arborizations in the subiculum and prefrontal cortex. These structural changes are associated with diminished memory performance. Hilar neurons of the hippocampus integrate spatial memory and are lost in dementia. They receive information from dentate gyrus neurons through dendrites, while they send axonal tracts to the CA3 region. Dendrites are complex structures of neurons that receive chemical information from presynaptic and postsynaptic terminals. Melatonin, the main product of the pineal gland, has neuroprotective actions through its free radical-scavenging properties and decreases neuronal apoptosis. Recently, we found that melatonin increases dendrite maturation and complexity in new neurons formed in the dentate gyrus of mice. In addition, in N1E-115 cultured cells, the indole stimulates early stages of neurite formation, a process that is known to antecede dendrite formation and maturation. Thus, in this study, we explored whether melatonin stimulates dendrite formation and complexity in the adult rat hippocampus in organotypic slice cultures, which is a model that preserves the hippocampal circuitry and their tridimensional organizations of connectivity. The effects of melatonin were studied in nonpathological conditions and in the absence of harmful agents. The results showed that the indole at nocturnal concentrations reached in the cerebrospinal fluid stimulates dendritogenesis at formation, growth, and maturation stages. Also, data showed that dendrites formed became competent to form presynaptic specializations. Evidence strongly suggests that melatonin may be useful in the treatment of neuropsychiatric diseases to repair the loss of dendrites and re-establish lost synaptic connections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cells, Cultured
  • Dendrites / drug effects*
  • Dendrites / metabolism
  • Dose-Response Relationship, Drug
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Immunohistochemistry
  • Male
  • Melatonin / pharmacology*
  • Neurogenesis / drug effects*
  • Rats
  • Rats, Wistar
  • Synapses / drug effects
  • Synapses / metabolism
  • Synaptophysin
  • Vesicular Transport Proteins / metabolism


  • Synaptophysin
  • Syp protein, rat
  • Vesicular Transport Proteins
  • Melatonin