Year-end Sale % OFF 
Abstract
Melatonin (MEL), the main product synthesized by the pineal gland, stimulates early and late stages of neurodevelopment in the adult brain. MEL increases dendrite length, thickness and complexity in the hilar and mossy neurons of hippocampus. Dendrite formation involves activation of Ca2+/Calmodulin (CaM)-dependent kinase II (CaMKII) by CaM. Previous work showed that MEL increased the synthesis and translocation of CaM, suggesting that MEL activates CaM-dependent enzymes by this pathway. In this work we investigated whether MEL stimulates dendrite formation by CaMKII activation in organotypic cultures from adult rat hippocampus. We found that the CaMKII inhibitor, KN-62, abolished the MEL stimulatory effects on dendritogenesis and that MEL increased the relative amount of CaM in the soluble fraction of hippocampal slices. Also, PKC inhibition abolished dendritogenesis, while luzindole, an antagonist of MEL receptors (MT1/2), partially blocked the effects of MEL. Moreover, autophosphorylation of CaMKII and PKC was increased in presence of MEL, as well as phosphorylation of ERK1/2. Our results indicate that MEL stimulates dendrite formation through CaMKII and the translocation of CaM to the soluble fraction. Dendritogenesis elicited by MEL also required PKC activation, and signaling through MT1/2 receptors was partially involved. Data strongly suggest that MEL could repair the loss of hippocampal dendrites that occur in neuropsychiatric disorders by increasing CaM levels and activation of CaMKII.
Highlights
One common feature in several neuropsychiatric disorders is that they present brain structural alterations
It was demonstrated that MEL increases dendritogenesis in adult interneurons of the hilar region of the hippocampus and in new neurons formed in the dentate gyrus of rodents [17,18]
It was shown that activation of CaM kinase II (CaMKII) is involved in dendrite formation and maturation [23,44]
Summary
One common feature in several neuropsychiatric disorders is that they present brain structural alterations. Ca2+/CaM kinase II (CaMKII) regulates multiple neuronal functions through phosphorylation of serine and threonine residues of its target proteins [22] It is abundant in the brain and participates in neurodevelopment, neurotransmitter synthesis and release, and cellular transport among other functions [23,24,25]. CaM available to activate the kinase can be augmented by synthesis or targeting to specific subcellular sites In this regard, MEL was shown to increase total cellular level and synthesis of CaM in epithelial cells after three days of incubation [36,37]. Data strongly suggests that MEL could repair the loss of synaptic connectivity in neuropsychiatric patients, by augmenting dendrite availability in the hippocampus of the adult brain
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
