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The role of melatonin in the neurodevelopmental etiology of schizophrenia: A study in human olfactory neuronal precursors
Author(s) -
GalvánArrieta Tania,
Trueta Citlali,
Cercós Montserrat G.,
ValdésTovar Marcela,
Alarcón Salvador,
Oikawa Julian,
ZamudioMeza Horacio,
BenítezKing Gloria
Publication year - 2017
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12421
Subject(s) - melatonin , endocrinology , medicine , biology , olfactory system , receptor , neuroscience
Dim light exposure of the mother during pregnancy has been proposed as one of the environmental factors that affect the fetal brain development in schizophrenia. Melatonin circulating levels are regulated by the environmental light/dark cycle. This hormone stimulates neuronal differentiation in the adult brain. However, little is known about its role in the fetal human brain development. Olfactory neuronal precursors ( ONP s) are useful for studying the physiopathology of neuropsychiatric diseases because they mimic all the stages of neurodevelopment in culture. Here, we first characterized whether melatonin stimulates neuronal differentiation in cloned ONP s obtained from a healthy control subject ( HCS ). Then, melatonin effects were evaluated in primary cultures of ONP s derived from a patient diagnosed with schizophrenia ( SZ ) and an age‐ and gender‐matched HCS . Axonal formation was evidenced morphologically by tau immunostaining and by GSK 3β phosphorylated state. Potassium‐evoked secretion was assessed as a functional feature of differentiated neurons. As well, we report the expression of MT 1/2 receptors in human ONP s for the first time. Melatonin stimulated axonal formation and ramification in cloned ONP s through a receptor‐mediated mechanism and enhanced the amount and velocity of axonal and somatic secretion. SZ ONP s displayed reduced axogenesis associated with lower levels of pGSK 3β and less expression of melatonergic receptors regarding the HCS ONP s. Melatonin counteracted this reduction in SZ cells. Altogether, our results show that melatonin signaling is crucial for functional differentiation of human ONP s, strongly suggesting that a deficit of this indoleamine may lead to an impaired neurodevelopment which has been associated with the etiology of schizophrenia.