Altered PLCβ/IP/Ca Signaling Pathway Activated by GPRCs in Olfactory Neuronal Precursor Cells Derived from Patients Diagnosed with Schizophrenia.

: Schizophrenia (SZ) is a multifactorial chronic psychiatric disorder with a worldwide prevalence of 1%. Altered expression of PLCβ occurs in SZ patients, suggesting alterations in the PLCβ/IP/Ca signaling pathway. This cascade regulates critical cellular processes in all cell types, including the neuronal lineage; however, there is scarce evidence regarding the functionality of this transduction signaling in neuronal cells derived from SZ patients.

Antidepressant-like and Beneficial Effects of a Neoponcirin-Beta-Cyclodextrin Inclusion Complex in Mice Exposed to Prolonged Stress.

Neoponcirin causes anxiolytic-like effects in mice when administered intraperitoneally but not orally. Neoponcirin is non-water-soluble and insoluble in solvents, and in medium acid, it isomerizes, reducing its bioavailability. To improve the pharmacological properties of neoponcirin, we formed a neoponcirin complex with beta-cyclodextrin (NEO/βCD), which was characterized by FT-IR, UV-Vis, and NMR, and their solubility profile.

Participation of Ca-Calmodulin-Dependent Protein Kinase II in the Antidepressant-Like Effects of Melatonin.

Melatonin (-acetyl-5-methoxytryptamine) is an indoleamine secreted by the pineal gland during the dark phase of the photoperiod. Its main function is the synchronization of different body rhythms with the dark-light cycle. Research on melatonin has significantly advanced since its discovery and we now know that it has considerable significance in various physiological processes, including immunity, aging, and reproduction.

Interaction of the Melatonin/Ca-CaM Complex with Calmodulin Kinase II: Physiological Importance.

Melatonin -acetyl-5-methoxytriptamine is an ancient molecule which synchronizes the internal biologic activity with the environmental photoperiod. It is synthesized by the pineal gland during the night and released to the general circulation, where it reaches nanomolar concentrations. The indolamine acts through melatonin receptors and binds to different proteins such as calmodulin: a phylogenetically conserved protein which is the main transductor of the calcium signaling.

Overexpression of miR-25 Downregulates the Expression of ROBO2 in Idiopathic Intellectual Disability.

Idiopathic intellectual disability () encompasses the cases of intellectual disability (ID) without a known cause and represents approximately 50% of all cases. Neural progenitor cells (NPCs) from the olfactory neuroepithelium (NEO) contain the same information as the cells found in the brain, but they are more accessible. Some miRNAs have been identified and associated with ID of known etiology.

Biomarkers in Alzheimer's Disease: Are Olfactory Neuronal Precursors Useful for Biomarker Research?

Alzheimer's disease (AD), as the main cause of dementia, affects millions of people around the world, whose diagnosis is based mainly on clinical criteria. Unfortunately, the diagnosis is obtained very late, when the neurodegenerative damage is significant for most patients. Therefore, the exhaustive study of biomarkers is indispensable for diagnostic, prognostic, and even follow-up support.

Melatonin: A Neurotrophic Factor?

Melatonin, -acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly depends on the endogenous circadian clock located in the suprachiasmatic nucleus and the retina's exposure to different light intensities. Among its most studied functions are the regulation of the waking-sleep rhythm and body temperature.

Behavioral and Fluorescent-Based Immunohistochemistry Protocols for Examining Antidepressant-Like Effects of Melatonin in Mice.

Antidepressants are characterized by their ability to decrease despair behavior assessed in mice as a decrease in immobility time in the forced swimming test (FST) (antidepressant-like behavior). This behavioral parameter is associated with increased neurogenesis in the dentate gyrus of the hippocampus of the rodents summitted to this test. Herein, we describe an optimized protocol used to characterize the melatonin antidepressant-like effect associated with its pro-neurogenic activity after an acute and a triple administration to mice measured by the FST and fluorescence-based immunohistochemistry in brain tissue, respectively.

Antidepressant Low Doses of Ketamine and Melatonin in Combination Produce Additive Neurogenesis in Human Olfactory Neuronal Precursors.

Melatonin (MEL), an indolamine with diverse functions in the brain, has been shown to produce antidepressant-like effects, presumably through stimulating neurogenesis. We recently showed that the combination of MEL with ketamine (KET), an NMDA receptor antagonist, has robust antidepressant-like effects in mice, at doses that, by themselves, are non-effective and have no adverse effects. Here, we show that the KET/MEL combination increases neurogenesis in a clone derived from human olfactory neuronal precursors, a translational pre-clinical model for effects in the human CNS.

Beneficial Effect of Melatonin Alone or in Combination with Glatiramer Acetate and Interferon β-1b on Experimental Autoimmune Encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model of multiple sclerosis (MS). Oxidative stress and chronic inflammation play a major role in the pathogenesis of MS and EAE. Melatonin, a neurohormone, has potent anti-inflammatory properties.

Further Evidence of the Melatonin Calmodulin Interaction: Effect on CaMKII Activity.

Melatonin (MEL) is a pleiotropic indolamine that reaches multiple intracellular targets. Among these, MEL binds to calmodulin (CaM) with high affinity. In presence of Ca, CaM binds to CaM-dependent kinase II (CaMKII).

Low Doses of Ketamine and Melatonin in Combination Produce Additive Antidepressant-like Effects in Mice.

Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, making it necessary to search for new antidepressant treatments. Ketamine, a phencyclidine hydrochloride derivative, given intravenously, induces a rapid antidepressant effect in humans.

Melatonin Rescues the Dendrite Collapse Induced by the Pro-Oxidant Toxin Okadaic Acid in Organotypic Cultures of Rat Hilar Hippocampus.

The pro-oxidant compound okadaic acid (OKA) mimics alterations found in Alzheimer's disease (AD) as oxidative stress and tau hyperphosphorylation, leading to neurodegeneration and cognitive decline. Although loss of dendrite complexity occurs in AD, the study of this post-synaptic domain in chemical-induced models remains unexplored. Moreover, there is a growing expectation for therapeutic adjuvants to counteract these brain dysfunctions.

Potential Use of Exfoliated and Cultured Olfactory Neuronal Precursors for In Vivo Alzheimer's Disease Diagnosis: A Pilot Study.

Histopathological hallmarks of dementia have been described postmortem in the brain of patients with Alzheimer's disease (AD). Tau, a microtubule associated protein, is abnormally arranged in neurofibrillary tangles. In living AD patients, total tau (t-tau) and hyperphosphorylated tau (p-tau) levels are increased in the cerebrospinal fluid obtained by lumbar puncture.

Purinergic Signaling Pathway in Human Olfactory Neuronal Precursor Cells.

Extracellular ATP and trophic factors released by exocytosis modulate proliferation, migration, and differentiation in multipotent stem cells (MpSC); however, the purinoceptors mediating this signaling remain uncharacterized in stem cells derived from the human olfactory epithelium (hOE). Our aim was to determine the purinergic pathway in isolated human olfactory neuronal precursor cells (hONPC) that exhibit MpSC features. Cloning by limiting dilution from a hOE heterogeneous primary culture was performed to obtain a culture predominantly constituted by hONPC.

Melatonin Effects on EEG Activity During Sleep Onset in Mild-to-Moderate Alzheimer's Disease: A Pilot Study.

There is evidence demonstrating that 5-mg of fast-release melatonin significantly reduces nocturnal sleep onset in patients with mild-to-moderate Alzheimer's disease (AD). However, the physiological mechanism that could promote sleep installation by melatonin in patients with AD is still poorly understood. The present pilot study was designed to analyze the effects of melatonin on cortical activity during the sleep onset period (SOP) in eight mild-to-moderate AD patients treated with 5-mg of fast-release melatonin.

The Timing of Melatonin Administration Is Crucial for Its Antidepressant-Like Effect in Mice.

Melatonin is synthesized by the pineal gland with a circadian rhythm in synchrony with the environmental light/dark cycle. A gradual increase in circulating levels of melatonin occur after lights off, reaching its maximum around the middle of the dark phase. Agonists of melatonin receptors have proved effectiveness as antidepressants in clinical trials.

Involvement of Melatonin in the Regulation of the Circadian System in Crayfish.

Melatonin (MEL) is an ancient molecule, broadly distributed in nature from unicellular to multicellular species. MEL is an indoleamine that acts on a wide variety of cellular targets regulating different physiological functions. This review is focused on the role played by this molecule in the regulation of the circadian rhythms in crayfish.

Circadian modulation of neuroplasticity by melatonin: a target in the treatment of depression.

Mood disorders are a spectrum of neuropsychiatric disorders characterized by changes in the emotional state. In particular, major depressive disorder is expected to have a worldwide prevalence of 20% in 2020, representing a huge socio-economic burden. Currently used antidepressant drugs have poor efficacy with only 30% of the patients in remission after the first line of treatment.

Cannabis Users Show Enhanced Expression of CB-5HT Receptor Heteromers in Olfactory Neuroepithelium Cells.

Cannabinoid CB1 receptors (CBR) and serotonergic 2A receptors (5HTR) form heteromers in the brain of mice where they mediate the cognitive deficits produced by delta-9-tetrahydrocannabinol. However, it is still unknown whether the expression of this heterodimer is modulated by chronic cannabis use in humans. In this study, we investigated the expression levels and functionality of CBR-5HTR heteromers in human olfactory neuroepithelium (ON) cells of cannabis users and control subjects, and determined their molecular characteristics through adenylate cyclase and the ERK 1/2 pathway signaling studies.

Primary cilia formation is diminished in schizophrenia and bipolar disorder: A possible marker for these psychiatric diseases.

Primary cilium (PC) is a microtubule-rich organelle that protrudes from the plasma membrane and acts as a cellular antenna sensing extracellular signals during brain development. DISC1 (Disrupted-in-Schizophrenia-1) is involved in PC formation and is considered a risk factor for neuropsychiatric disorders. We have previously described altered subcellular distribution of DISC1 and an aberrant microtubule organization in olfactory neuronal precursors (ONP) obtained from schizophrenia (SCZ) and bipolar disorder (BD) patients.

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

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.

The role of melatonin in the neurodevelopmental etiology of schizophrenia: A study in human olfactory neuronal precursors.

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.