Abnormally Increased Secretion in Olfactory Neuronal Precursors from a Case of Schizophrenia Is Modulated by Melatonin: A Pilot Study

Abstract

The alterations that underlie the pathophysiology of schizophrenia (SCZ) include the dysregulation of structural and functional properties of neurons. Among these, the secretion of neurotransmitters and hormones, which plays a key role for neuronal communication and development, is altered. Neuronal precursors from the human olfactory epithelium have been recently characterized as a reliable model for studying the etiopathogenesis of neuropsychiatric diseases. Our previous work has shown that melatonin enhances the development of morphological and functional features of cloned olfactory neuronal precursors (ONPs) from a healthy subject. In this work we found that primary cultures of ONPs obtained from a schizophrenic patient display an increased potassium-evoked secretion, when compared with ONPs from an age- and gender-matched healthy control subject (HCS). Secretion was evaluated by FM1-43 fluorescence cumulative changes in response to depolarization. Interestingly, a 12 h-melatonin treatment modulated the abnormally increased secretion in SCZ ONPs and brought it to levels similar to those found in the HCS ONPs. Our results suggest that the actin cytoskeleton might be a target for melatonin effects, since it induces the thickening of actin microfilament bundles. Further research will address the mechanisms by which melatonin modulates neurochemical secretion from ONPs.

Protective Effects of Melatonin on Neurogenesis Impairment in Neurological Disorders and Its Relevant Molecular Mechanisms

“…Induction of seizures to a rat mother led to early embryonic neurogenesis and delayed maturation of newborn neurons in the cerebellum and the Cornus ammonis 1 (CA1) region of the hippocampus in PND0 offspring [ 114 , 115 ]. Olfactory NSCs isolated from schizophrenia (SCZ) patients also exhibited an abnormal increase in the potassium-evoked secretion when compared with the NSCs of the healthy control [ 116 ]. Interestingly, melatonin treatment could reverse all the abnormalities caused by seizures [ 114 , 115 , 116 ] ( Table 12 and Table 13 ).…”

“…Olfactory NSCs isolated from schizophrenia (SCZ) patients also exhibited an abnormal increase in the potassium-evoked secretion when compared with the NSCs of the healthy control [ 116 ]. Interestingly, melatonin treatment could reverse all the abnormalities caused by seizures [ 114 , 115 , 116 ] ( Table 12 and Table 13 ).…”

Purinergic Signaling Pathway in Human Olfactory Neuronal Precursor Cells

“…The culture of stem cells obtained from the human olfactory epithelium (hOE) had enabled the study of diverse cellular processes that are dependent on Ca 2+ signaling in neuronal cells, for instance, the olfactory transduction in sensory neurons [12], axonogenesis [13, 14], exocytosis triggered by depolarization of the plasma membrane [15], and microtubule organization [16]. Therefore, this cell culture could be an ex vivo suitable model to study the Ca 2+ -dependent mechanisms underlying proliferation [17], migration [18], or differentiation [19] in neuronal precursor cells.…”

Human olfactory mesenchymal stromal cells co-expressing horizontal basal and ensheathing cell proteins in culture

“…There is experimental evidence that neural cells obtained in vitro from explants of olfactory mucosa may be used for regenerative purposes (11,12,14,(19)(20)(21)(22). Recent evidence has shown that human olfactory mucosa stromal cells (SC) may offer unique properties as a peripheral reporter in some neuropsychiatric disorders (23)(24)(25)(26)(27) and chronical diseases such as Alzheimer's (28,29) and Parkinson (30).…”