Microtubule organization and L-type voltage-activated calcium current in olfactory neuronal cells obtained from patients with schizophrenia and bipolar disorder

Solís‐Chagoyán, Héctor; Calixto, Eduardo; Figueroa, Alejandra; Montaño, Luis M.; Berlanga, Carlos; Rodríguez-Verdugo, M.S.; Romo, F.; Jiménez, Mariela; Gurrola, C. Zepeda; Riquelme, Agustín; Benítez‐King, Gloria

doi:10.1016/j.schres.2012.11.035

Cited by 44 publications

(52 citation statements)

References 45 publications

(53 reference statements)

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“…By contrast, SZ ONPs are more spread than HCS ONPs and do not show a clear bipolar shape (Figure B). In addition, cavities devoid of staining (Figure B, arrow) were clearly observed in SZ ONPs, as reported before . In the presence of 10 −5 mol/L melatonin, the ONPs of the HCS clearly developed a long axon (Figure A’) and SZ ONPs acquired a bipolar shape and started to develop the axon (Figure B’).…”

Section: Resultssupporting

confidence: 81%

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

Galván-Arrieta

Trueta²,

Cercós³

et al. 2017

Journal of Pineal Research

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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 (ONPs) 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 ONPs obtained from a healthy control subject (HCS). Then, melatonin effects were evaluated in primary cultures of ONPs 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 GSK3β phosphorylated state. Potassium-evoked secretion was assessed as a functional feature of differentiated neurons. As well, we report the expression of MT1/2 receptors in human ONPs for the first time. Melatonin stimulated axonal formation and ramification in cloned ONPs through a receptor-mediated mechanism and enhanced the amount and velocity of axonal and somatic secretion. SZ ONPs displayed reduced axogenesis associated with lower levels of pGSK3β and less expression of melatonergic receptors regarding the HCS ONPs. Melatonin counteracted this reduction in SZ cells. Altogether, our results show that melatonin signaling is crucial for functional differentiation of human ONPs, strongly suggesting that a deficit of this indoleamine may lead to an impaired neurodevelopment which has been associated with the etiology of schizophrenia.

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Section: Resultssupporting

confidence: 81%

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

Galván-Arrieta

Trueta²,

Cercós³

et al. 2017

Journal of Pineal Research

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“…Furthermore, these SZ cells showed altered levels of histone methylation in several gene groups involved in cellular protection against oxidative stress, suggesting a potential role of oxidative stress in the pathophysiology of SZ [17]. Cultured cells established via nasal brush swab showed altered microtubular organization, together with decreased function of L-type Ca 2+ channels in patients with SZ relative to controls [47]. An OE explant (non-dissociated) culture from SZ patients showed increased stability of microtubules and a greater percentage of cells with intact microtubules [40], as well as a higher ratio of mitotic cells to dying and quiescent cells [41, 48].…”

Section: Findings From Oe-derived Tissue/cell Models Obtained From Szmentioning

confidence: 99%

Application of olfactory tissue and its neural progenitors to schizophrenia and psychiatric research

Lavoie

Sawa²,

Ishizuka³

2017

Current Opinion in Psychiatry

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Purpose of review The goal of this review article is to introduce olfactory epithelium (OE)-derived cell/tissue models as a promising surrogate system to study the molecular mechanisms implicated in schizophrenia (SZ) and other neuropsychiatric disorders. Here we particularly focus the utility of their neural progenitors. Recent findings Recent investigations of the pathophysiology of SZ using OE-derived tissue/cell models have provided insights about SZ-associated alterations in neurodevelopment, stress response, and gene/protein expression regulatory pathways. Summary The OE retains the capacity for lifelong neurogenesis and regeneration, because of the presence of neural stem cells and progenitors. Thus, both mature neurons and neural progenitors can be obtained from the OE without the need for genetic reprogramming and related confounds. Furthermore, the OE is highly scalable resource in translational settings. Here we also demonstrate recent findings from research using OE-derived tissue/cell models in SZ and other brain disorders. In summary, we propose that the OE as a promising resource to study neural molecular and cellular signatures relevant to the pathology of SZ and other mental disorders.

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“…For example, in cultured HEK cells, haloperidol acutely blocks T-type voltage-gated calcium channels in a dose-dependent manner (Santi et al, 2002), while it remains unclear whether antipsychotics also affect voltage-gated calcium channels in neurons. Solís-Chagoyán et al (2013) recently reported that Ca 2+ currents mediated by L-type voltage-gated calcium channels recorded in olfactory neuroepithelial cells obtained from patients with schizophrenia were 50% smaller than those from healthy subjects. Because these patients with schizophrenia were taking antipsychotics, the finding does not simply support the genetic studies suggesting that dysfunction of L-type voltage-gated calcium channels occurs in patients with schizophrenia.…”

Section: Schizophrenia and Intracellular Ca2+ Signalingmentioning

confidence: 99%

Microglial intracellular Ca2+ signaling as a target of antipsychotic actions for the treatment of schizophrenia

Mizoguchi

Kato

Horikawa

et al. 2014

Front. Cell. Neurosci.

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Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and neurotrophic factors when they are activated in response to immunological stimuli. Recent reports show that pathophysiology of schizophrenia is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling, which is mainly controlled by the endoplasmic reticulum (ER), is important for microglial functions such as release of NO and cytokines, migration, ramification and deramification. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of schizophrenia, while it remains unclear how typical or atypical antipsychotics affect intracellular Ca2+ mobilization in microglial cells. This mini-review article summarizes recent findings on cellular mechanisms underlying the characteristic differences in the actions of antipsychotics on microglial intracellular Ca2+ signaling and reinforces the importance of the ER of microglial cells as a target of antipsychotics for the treatment of schizophrenia.

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Microtubule organization and L-type voltage-activated calcium current in olfactory neuronal cells obtained from patients with schizophrenia and bipolar disorder

Cited by 44 publications

References 45 publications

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

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

Application of olfactory tissue and its neural progenitors to schizophrenia and psychiatric research

Microglial intracellular Ca2+ signaling as a target of antipsychotic actions for the treatment of schizophrenia

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