18 results on '"Valdés-Tovar, Marcela"'
Search Results
2. Potential of olfactory neuroepithelial cells as a model to study schizophrenia: A focus on GPCRs (Review).
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Sánchez-Florentino, Zuly A., Romero-Martínez, Bianca S., Flores-Soto, Edgar, Serrano, Héctor, Montaño, Luis M., Valdés-Tovar, Marcela, Calixto, Eduardo, Aquino-Gálvez, Arnoldo, López-Riquelme, Germán O., Alvarado, Ramón, Argueta, Jesús, Solís-Chagoyán, Héctor, and Sommer, Bettina
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- 2024
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3. Circadian modulation of neuroplasticity by melatonin: a target in the treatment of depression.
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Valdés‐Tovar, Marcela, Estrada‐Reyes, Rosa, Solís‐Chagoyán, Héctor, Argueta, Jesús, Dorantes‐Barrón, Ana María, Quero‐Chávez, Daniel, Cruz‐Garduño, Ricardo, Cercós, Montserrat G., Trueta, Citlali, Oikawa‐Sala, Julián, Dubocovich, Margarita L., Benítez‐King, Gloria, Valdés-Tovar, Marcela, Estrada-Reyes, Rosa, Solís-Chagoyán, Héctor, Dorantes-Barrón, Ana María, Quero-Chávez, Daniel, Cruz-Garduño, Ricardo, Oikawa-Sala, Julián, and Benítez-King, Gloria
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MELATONIN , *MENTAL depression , *THERAPEUTICS , *NEUROPLASTICITY , *CIRCADIAN rhythms , *ANTIDEPRESSANTS , *GLUTAMIC acid metabolism , *HIPPOCAMPUS (Brain) - Abstract
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. Importantly, mood disorder patients present uncoupling of circadian rhythms. In this regard, melatonin (5-methoxy-N-acetyltryptamine), an indolamine synthesized by the pineal gland during the night, contributes to synchronization of body rhythms with the environmental light/dark cycle. In this review, we describe evidence supporting antidepressant-like actions of melatonin related to the circadian modulation of neuroplastic changes in the hippocampus. We also present evidence for the role of melatonin receptors and their signalling pathways underlying modulatory effects in neuroplasticity. Finally, we briefly discuss the detrimental consequences of circadian disruption on neuroplasticity and mood disorders, due to the modern human lifestyle. Together, data suggest that melatonin's stimulation of neurogenesis and neuronal differentiation is beneficial to patients with mood disorders. LINKED ARTICLES: This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc. [ABSTRACT FROM AUTHOR]
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- 2018
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4. W72. TOLL-LIKE RECEPTOR 1, 2 AND 6 GENE EXPRESSION IN MONOCYTES OF PATIENTS WITH SCHIZOPHRENIA.
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Ramirez, Carlo Esteban Sotelo, Valdés-Tovar, Marcela, Hoyos, Julio Uriel Zaragoza, Miranda-Labra, Roxana, and Camarena, Beatriz
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GENE expression , *TOLL-like receptors , *PEOPLE with schizophrenia , *MONONUCLEAR leukocytes , *GENOME-wide association studies , *PATTERN perception receptors - Abstract
Genome-wide association studies (GWAS) support a relationship between regulatory genes of the immune response and schizophrenia. Toll-like receptors (TLRs) are a main family of pattern recognition receptors involved in triggering the innate immune response. We identified association between the TLR1, TLR2 and TLR6 genes and the risk of developing schizophrenia. Therefore, the aim of the present study was evaluated the effect of the risk variants in TLR1, TLR2 and TLR6 in the gene expression levels and the amount of these proteins measured in peripheral blood mononuclear cells of patients with schizophrenia compared with a control group. We included 24 Mexican patients with schizophrenia from INPRFM, and 24 healthy controls. Positive selection of CD14+ cells with MACS® Technology was used to obtain monocytes. RNA was extracted from monocytes using TRIzolTM. cDNA was synthesized with SuperScriptTM IV VILOTM Master Mix. We analyzed the gene expression of TLR1, TLR2, TLR6 and ACTB as housekeeping gene with qRT-PCR with TaqMan probes. Protein was separated by SDS-PAGE and electro-transferred onto PVDF membrane. Expression of TLR1, TLR2 and TLR6 was analyzed by Western Blot with specific antibodies for each receptor. Immunoreactive bands were developed with Immobilon® Western reagent and detected with ChemiDoc MP Imaging System. The gene expression analysis showed that TLR1, TLR2 and TLR6 was downregulated in patients with schizophrenia, compared to controls (p=0.0009). The analysis of gene expression by alleles identified an under-expression of TLR1 in patient carriers of the G allele (p = 0.0001). Also, an increase in the expression of TLR2 (p = 0.0002) and TLR6 (p < 0.05) was observed in patient carriers of the variants of interest compared with the control subjects. Differences in protein expression of TLR6 was observed between patients (D.O.x mm2 =600) and controls (D.O.x mm2 =190). The present study replicated the findings reporting downregulation gene expression in patients with schizophrenia. Also, alterations in protein expression have been reported in patients with schizophrenia, compared with controls. Moreover, this is the first study that analyzed the impact of risk alleles of TLR genes and changes in the gene expression levels in Mexican patients with schizophrenia. Our preliminary findings could indicate that the gene expression levels are given by other factors and not for the risk alleles previously identified. Therefore, our findings suggest that TLR1, TLR2 and TLR6 play an important role in the pathophysiology of schizophrenia. However, these findings should be analyzed in a larger sample size and carry out functional studies to identify alterations in TLR genes supporting the role of innate immune response in schizophrenia. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Purinergic Signaling Pathway in Human Olfactory Neuronal Precursor Cells.
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Solís-Chagoyán, Héctor, Flores-Soto, Edgar, Valdés-Tovar, Marcela, Cercós, Montserrat G., Calixto, Eduardo, Montaño, Luis M., Barajas-López, Carlos, Sommer, Bettina, Aquino-Gálvez, Arnoldo, Trueta, Citlali, and Benítez-King, Gloria A.
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OLFACTORY receptors ,MULTIPOTENT stem cells ,FLUORESCENT probes ,STEM cells ,CELLS ,TRANSCRIPTION factors - Abstract
Extracellular ATP and trophic factors released by exocytosis modulate in vivo 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. Effectiveness of cloning to isolate MpSC-like precursors was corroborated through immunodetection of specific protein markers and by functional criteria such as self-renewal, proliferation capability, and excitability of differentiated progeny. P2 receptor expression in hONPC was determined by Western blot, and the role of these purinoceptors in the ATP-induced exocytosis and changes in cytosolic Ca
2+ ([Ca2+ ]i ) were evaluated using the fluorescent indicators FM1-43 and Fura-2 AM, respectively. The clonal culture was enriched with SOX2 and OCT3/4 transcription factors; additionally, the proportion of nestin-immunopositive cells, the proliferation capability, and functionality of differentiated progeny remained unaltered through the long-term clonal culture. hONPC expressed P2X receptor subtypes 1, 3-5, and 7, as well as P2Y2, 4, 6, and 11; ATP induced both exocytosis and a transient [Ca2+ ]i increase predominantly by activation of metabotropic P2Y receptors. Results demonstrated for the first time that ex vivo-expressed functional P2 receptors in MpSC-like hONPC regulate exocytosis and Ca2+ signaling. This purinergic-triggered release of biochemical messengers to the extracellular milieu might be involved in the paracrine signaling among hOE cells. [ABSTRACT FROM AUTHOR]- Published
- 2019
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6. The role of melatonin in the neurodevelopmental etiology of schizophrenia: A study in human olfactory neuronal precursors.
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Galván‐Arrieta, Tania, Trueta, Citlali, Cercós, Montserrat G., Valdés‐Tovar, Marcela, Alarcón, Salvador, Oikawa, Julian, Zamudio‐Meza, Horacio, and Benítez‐King, Gloria
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SCHIZOPHRENIA ,MELATONIN ,NEURAL development ,MENTAL illness ,POTASSIUM - Abstract
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. [ABSTRACT FROM AUTHOR]
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- 2017
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7. Abnormally Increased Secretion in Olfactory Neuronal Precursors from a Case of Schizophrenia Is Modulated by Melatonin: A Pilot Study.
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Cercós, Montserrat G., Galván-Arrieta, Tania, Valdés-Tovar, Marcela, Solís-Chagoyán, Héctor, Argueta, Jesús, Benítez-King, Gloria, and Trueta, Citlali
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SCHIZOPHRENIA ,EXOCYTOSIS ,MELATONIN ,CYTOSKELETON ,SECRETORY granules ,NEURONS ,NEUROTRANSMITTERS - 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. [ABSTRACT FROM AUTHOR]
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- 2017
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8. Olanzapine-induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin.
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Romo‐Nava, Francisco, Buijs, Frederik N., Valdés‐Tovar, Marcela, Benítez‐King, Gloria, Basualdo, MariCarmen, Perusquía, Mercedes, Heinze, Gerhard, Escobar, Carolina, and Buijs, Ruud M.
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MELATONIN ,CARDIOVASCULAR disease treatment ,OLANZAPINE ,ANTIPSYCHOTIC agents ,SUPRACHIASMATIC nucleus ,DRUG efficacy ,THERAPEUTICS - Abstract
Second generation antipsychotics ( SGA) are associated with adverse cardiometabolic side effects contributing to premature mortality in patients. While mechanisms mediating these cardiometabolic side effects remain poorly understood, three independent studies recently demonstrated that melatonin was protective against cardiometabolic risk in SGA-treated patients. As one of the main target areas of circulating melatonin in the brain is the suprachiasmatic nucleus ( SCN), we hypothesized that the SCN is involved in SGA-induced early cardiovascular effects in Wistar rats. We evaluated the acute effects of olanzapine and melatonin in the biological clock, paraventricular nucleus and autonomic nervous system using immunohistochemistry, invasive cardiovascular measurements, and Western blot. Olanzapine induced c-Fos immunoreactivity in the SCN followed by the paraventricular nucleus and dorsal motor nucleus of the vagus indicating a potent induction of parasympathetic tone. The involvement of a SCN-parasympathetic neuronal pathway after olanzapine administration was further documented using cholera toxin-B retrograde tracing and vasoactive intestinal peptide immunohistochemistry. Olanzapine-induced decrease in blood pressure and heart rate confirmed this. Melatonin abolished olanzapine-induced SCN c-Fos immunoreactivity, including the parasympathetic pathway and cardiovascular effects while brain areas associated with olanzapine beneficial effects including the striatum, ventral tegmental area, and nucleus accumbens remained activated. In the SCN, olanzapine phosphorylated the GSK-3β, a regulator of clock activity, which melatonin prevented. Bilateral lesions of the SCN prevented the effects of olanzapine on parasympathetic activity. Collectively, results demonstrate the SCN as a key region mediating the early effects of olanzapine on cardiovascular function and show melatonin has opposing and potentially protective effects warranting additional investigation. [ABSTRACT FROM AUTHOR]
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- 2017
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9. Voltage-Activated Calcium Channels as Functional Markers of Mature Neurons in Human Olfactory Neuroepithelial Cells: Implications for the Study of Neurodevelopment in Neuropsychiatric Disorders.
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Solís-Chagoyán, Héctor, Flores-Soto, Edgar, Reyes-García, Jorge, Valdés-Tovar, Marcela, Calixto, Eduardo, Montaño, Luis M., and Benítez-King, Gloria
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NEUROBEHAVIORAL disorders ,PATHOLOGICAL physiology ,SCHIZOPHRENIA ,CALCIUM channels ,NEURONS - Abstract
In adulthood, differentiation of precursor cells into neurons continues in several brain structures as well as in the olfactory neuroepithelium. Isolated precursors allow the study of the neurodevelopmental process in vitro. The aim of this work was to determine whether the expression of functional Voltage-Activated Ca
2+ Channels (VACC) is dependent on the neurodevelopmental stage in neuronal cells obtained from the human olfactory epithelium of a single healthy donor. The presence of channel-forming proteins in Olfactory Sensory Neurons (OSN) was demonstrated by immunofluorescent labeling, and VACC functioning was assessed by microfluorometry and the patch-clamp technique. VACC were immunodetected only in OSN. Mature neurons responded to forskolin with a five-fold increase in Ca2+ . By contrast, in precursor cells, a subtle response was observed. The involvement of VACC in the precursors' response was discarded for the absence of transmembrane inward Ca2+ movement evoked by step depolarizations. Data suggest differential expression of VACC in neuronal cells depending on their developmental stage and also that the expression of these channels is acquired by OSN during maturation, to enable specialized functions such as ion movement triggered by membrane depolarization. The results support that VACC in OSN could be considered as a functional marker to study neurodevelopment. [ABSTRACT FROM AUTHOR]- Published
- 2016
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10. Constant light suppresses production of Met-enkephalin-containing peptides in cultured splenic macrophages and impairs primary immune response in rats.
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Valdés-Tovar, Marcela, Escobar, Carolina, Solís-Chagoyán, Héctor, Asai, Miguel, and Benítez-King, Gloria
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ENKEPHALINS , *PEPTIDES , *MACROPHAGES , *PHYSIOLOGICAL effects of light , *IMMUNOREGULATION , *SPLEEN , *LABORATORY rats - Abstract
The light-dark cycle is an environmental factor that influences immune physiology, and so, variations of the photoperiod length result in altered immune responsivity. Macrophage physiology comprises a spectrum of functions that goes from host defense to immune down-regulation, in addition to their homeostatic activities. Macrophages also play a key role in the transition from innate to adaptive immune responses. Met-enkephalin (MEnk) has been recognized as a modulator of macrophage physiology acting in an autocrine or paracrine fashion to influence macrophage activation, phenotype polarization and production of cytokines that would enhance lymphocyte activation at early stages of an immune response. Previously it was shown that splenic MEnk tissue content is reduced in rats exposed to constant light. In this work, we explored whether production of Met-enkephalin-containing peptides (MECPs) in cultured splenic macrophages is affected by exposure of rats to a constant light regime. In addition, we explored whether primary immune response was impaired under this condition. We found that in rats, 15 days in constant light was sufficient to disrupt their general activity rhythm. Splenic MEnk content oscillations and levels were also blunted throughout a 24-h period in animals subjected to constant light. In agreement, de novo synthesis of MECPs evaluated through incorporation of 35S-methionine was reduced in splenic macrophages from rats exposed to constant light. Moreover, MECPs immunocytochemistry showed a decrease in the intracellular content and lack of granule-like deposits in this condition. Furthermore, we found that primary T-dependent antibody response was compromised in rats exposed to constant light. In those animals, pharmacologic treatment with MEnk increased IFN-γ-secreting cells. Also, IL-2 secretion from antigen-stimulated splenocytes was reduced after incubation with naloxone, suggesting that immune-derived opioid peptides and stimulation of opioid receptors are involved in this process. Thus, the immune impairment observed from early stages of the response in constant light-subjected rats, could be associated with reduced production of macrophage-derived enkephalins, leading to a sub-optimal interaction between macrophages and lymphocytes in the spleen and the subsequent deficiency in antibody production. [ABSTRACT FROM AUTHOR]
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- 2015
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11. Melatonin Stimulates Dendrite Formation and Complexity in the Hilar Zone of the Rat Hippocampus: Participation of the Ca++/Calmodulin Complex.
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Domínguez-Alonso, Aline, Valdés-Tovar, Marcela, Solís-Chagoyán, Héctor, and Benítez-King, Gloria
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ANIMAL models of brain diseases , *PHYSIOLOGICAL effects of melatonin , *DENDRITES , *PROTEIN synthesis , *CALCIUM-dependent protein kinase , *HIPPOCAMPUS (Brain) , *NEURODEVELOPMENTAL treatment - 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. [ABSTRACT FROM AUTHOR]
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- 2015
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12. La melatonina como un factor promotor de la diferenciación neuronal: implicaciones en el tratamiento de las demencias.
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Benítez-King, Gloria, Valdés-Tovar, Marcela, Maya-Ampudia, Vanessa, Jiménez-Rubio, Graciela, Domínguez-Alonso, Aliñe, Riquelme, Agustín, Galván-Arrieta, Tania, Solís-Chagoyán, Héctor, Alarcón, Salvador, Moreno, Julia, Ugalde, Óscar, and Berlanga, Carlos
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HEALTH outcome assessment , *TREATMENT of dementia , *PHYSIOLOGICAL effects of melatonin , *BIOMARKERS , *DEVELOPMENTAL neurobiology , *OXIDATIVE stress , *ANTIOXIDANTS , *AMYLOID - Abstract
Dementias are progressive and neurodegenerative neuropsychiatric disorders, with a high worldwide prevalence. These disorders affect memory and behavior, causing impairment in the performance of daily activities and general disability in the elders. Cognitive impairment in these patients is related to anatomical and structural alterations at cellular and sub-cellular levels in the Central Nervous System. In particular, amyloid plaques and neurofibrillar tangles have been defined as histopathological hallmarks of Alzheimer's disease. Likewise, oxidative stress and neuroinflammation are implicated in the etiology and progression of the disease. Neuronal precursors from human olfactory neuroepithelium have been recently characterized as an experimental model to identify neuropsychiatric disease biomarkers. Moreover, this model not only allows the study of neuropsychiatric physiopathology, but also the process of neurodevelopment at cellular, molecular and pharmacological levels. This review gathers the evidence to support the potential therapeutic use of melatonin for dementias, based on its antioxidant properties, its anti-inflammatory effect in the brain, and its ability to inhibit both tau hyper-phosphorylation and amyloid plaque formation. Furthermore, since melatonin stimulates neurogenesis, and promotes neuronal differentiation by inducing the early stages of neurogenesis and dendrite formation, it has been suggested that melatonin could be useful to counteract the cognitive impairment in dementia patients. [ABSTRACT FROM AUTHOR]
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- 2013
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13. La melatonina induce la síntesis y liberación de las encefalinas en el cerebro de la rata.
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Asai, Miguel, Valdés-Tovar, Marcela, Matamoros-Trejo, Gilberto, and García, David
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ENKEPHALINS , *OPIOID peptides , *NEUROSCIENCES , *HOMEOSTASIS , *CIRCADIAN rhythms , *LABORATORY rats , *HORMONE research , *MELATONIN - Abstract
Since enkephalins discovery in 1975, several opioid peptides have been included in neuroscience research. Enkephalins have been involved in the homeostasis maintenance of the organism, mostly with cellular and molecular mechanisms implicated in antinociception and narcotic responses. Moreover, enkephalins have been shown to be involved in the control of stress, regulation of cardiovascular functions, modulating primary immune responses, in addition to cellular differentiation processes. As opioid peptides appear to modulate several bioactivities and physiological responses in organisms, this posits that several modifications should occur during their synthesis, cell release, and receptor binding in target cells. At present, it has been demonstrated that the endogenous opioid system (EOS), displays a circadian rhythm, in which its tissue content, presynaptic release, and receptor's number reaches its maximal concentration during the dark phase (24:00h) and the minimal during the early morning (05:00 h). Recently, our group reported that functional pinealectomy disrupts the enkephalin circadian rhythm and significantly reduces the tissue content of opioid peptides in the rat brain. However, the effect was shown to be specific to the hour along the 24h daytime. There were no significant changes during the light period, only during the dark period (01:00h), when the enkephalin tissue content decreased in the experimental group. The effect was reverted when pinealectomized rats were injected with single doses of melatonin (MEL) (150μg/kg i.p.). If the lack of melatonin in the rat brain significantly reduced the enkephalin tissue content, and its exogenous administration re-established the enkephalin tissue levels, it is possible that the hormone is involved in the enkephalin synthesis. In this paper we provide further evidence that supports the relation between melatonin and opioid peptides synthesis and release. In addition, we studied the effect of darkness and melatonin administration in enkephalin tissue levels. Finally, we analyzed the luzindole effect as a melatonin receptor antagonist in the pinealectomized rat brain. Subjects: Male Wistar rats were housed in a light and temperature controlled room. Water and pellet food were available ad libitum. This group was subdivided in: 1. Functional pinealectomy group (FP). Rats were housed individually during 15 days in a room with continuous light (<50lux). 2. FP rats were housed in a dark room during four or six hours. 3. FP rats were injected with melatonin (150, 300, 600μg/kg s.c.). 4. FP rats were injected with Luzindole (187.5, 375, 750μg/kg i.p.). After 30 min, the animals were injected with melatonin (150μg/kg). 5. FP rats were injected with melatonin (800μg/kg) and subjected to the in vitro release processes. The rats were sacrificed by decapitation and the blood collected for melatonin serum determination. The brains were removed and processed for an analytical preparative procedure for the enkephalin determination by radioimmunoassay technique. The in vitro release methodology was performed as follows: tissue samples were homogenized by applying 8 strokes with a Thomas grinder system. The homogenates were centrifuged at 4,000rpm, 4°C during 10 min. Supernatants were recovered and centrifuged at 12,000rpm at 4°C for 20 min. Supernatants were discarded and pellets were resuspended in the homogeneization buffer (1:9 w/v). Samples were placed on top of a Percoll gradient density (23%, 15%, and 10%) and centrifuged at 20,000 rpm at 4°C for 25min. The synaptosomal enriched fraction (15-23%) was obtained and diluted in 1mL of Krebs buffer (mM: NaCl 119, KCl 4.6, CaCl2·2H2O 1.25, KH2PO4 0.85 MgSO4 0.84, NaHCO3 24.8, sucrose 10). Buffer was gasified with a mixture of C02 95% and O2 5%, pH 7.4. 800μL aliquots were placed into plastic chambers. After 20 min of stabilization with Krebs buffer, three different superfusates were collected: 1. basal, 2. potassium [50mM], and 3. post-stimulus (Krebs buffer without potassium). Samples were collected into HCl 0.1N, boiled and subsequently loaded into Amberlite XAD-2 columns (8×0.7cm) for solid-phase peptide extraction. The flow rate was held constant at 0.5 mL min-1 and elution of the whole peptide fraction was carried out using a continuous gradient with absolute methanol. Eluted samples were lyophilized and resuspended in 2mL of distilled water and finally stored at -20°C for further quantification of IR-Enkephalin using standard radioimmunoassay procedures. The results showed that functional pinealectomy reduced the opioid tissue content in the different brain structures assayed. The lack of melatonin significantly decreased the enkephalin tissue content when compared to the control group. However, tissue levels of enkephalin material were completely restored after four and six hours of administration of different doses of exogenous melatonin administration to the rats. As continuous light decreases the melatonin content in the brain, darkness should be able to counteract the aforementioned effect. Our results showed that tissue levels of enkephalin material were increased over 200% and 300%, after exposing animals to a four or six-hour period of darkness, when compared to animals exposed to continuous light. Luzindole was used to abolish any melatonin activity via activation of its membrane brain receptors. Our experiments showed that different doses of the antagonist were not able to obliterate the increased content of opioid peptides induced with melatonin administration in the tested brain tissues. Finally, enkephalin release showed a significant decrease in pinealectomized rats, showing a complete restoration of released peptide levels as shown by control group, after hormone administration. Thus, melatonin appears to counteract the neuronal decrease of the releasable pool of opioid peptide within the nerve terminals, reaching the released rate values detected in the control group. Our results suggest four relevant features: 1. Functional pinealectomy induces a significant decrease in the tissue content of opioid peptide material that seems to correlate with a decrease in the presynaptic release of enkephalins. 2. Darkness and MEL administration counteracted the light induced effects, namely the decreased content of opioid peptide material in tissue and the reduced peptide release from nerve terminals. 3. Nonetheless, the presence of luzindole was not able to inhibit the synthesis of opioid peptides. Melatonin is a hormone that synchronizes cell activity with photoperiod. Beyond this physiological property, MEL has been related to neuropeptide synthesis. Previous reports have shown that surgical or functional pinealectomy reduces the Met-Enkephalin tissue content in the rat brain. Also, it has been demonstrated that MEL stimulates the Proopiomelanocortin (POMC) gene expression in the immune system. In this paper, we showed further evidence that melatonin participates in the biosynthetic regulation of opioid peptides. Dark stimulation after continuous light exposure on rats produced an increase of tissue content of enkephalin above 300%, when compared with tested animals subjected to functional pinealectomy. Similar results were obtained with the exogenous melatonin administration. These evidences support the hypothesis that hormone treatment may be able to interact with protein kinase C (in the active-state of the enzyme). In addition, the hormone could modulate the cellular responses of several transcription factors (c-Fos, c-Jun, AP-1) responsible for the enkephalin gene expression. On the other hand, rats exposed to MEL-receptor antagonist luzindole, injected before MEL administration, showed that the tissue content of opioid peptide was not totally abolished by the melatonin antagonist. It has been proposed that melatonin not only interacts with its membrane receptor, but it is able to cross the cytoplasmic membrane and interact directly with the intracellular signal transduction system via the biomolecules that operate within. In conclusion, the physiology of melatonin appears to control the synthesis and presynaptic release of the endogenous opioid system in the rat brain. [ABSTRACT FROM AUTHOR]
- Published
- 2010
14. EFECTO DE LA MELATONINA SOBRE LA CONCENTRACIÓN DE PÉPTIDOS OPIOIDES EN EL SISTEMA INMUNE DE LA RATA.
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Valdés-Tovar, Marcela, Asal, Miguel, and Matamoros-Trejo, Gilberto
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- 2003
15. Low Doses of Ketamine and Melatonin in Combination Produce Additive Antidepressant-like Effects in Mice.
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Estrada-Reyes, Rosa, Quero-Chávez, Daniel B., Trueta, Citlali, Miranda, Armida, Valdés-Tovar, Marcela, Alarcón-Elizalde, Salvador, Oikawa-Sala, Julián, Argueta, Jesús, Constantino-Jonapa, Luis A., Muñoz-Estrada, Jesús, Dubocovich, Margarita L., and Benítez-King, Gloria
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KETAMINE ,MENTAL depression ,MELATONIN ,PINEAL gland ,MICE - Abstract
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. In mice, it causes increased neurogenesis and antidepressant-like effects. However, it also produces psychomimetic effects in humans and in rodents increases the locomotor activity. In contrast, melatonin, a hormone secreted by the pineal gland and synthesized in extrapineal sites, increases new neuron formation and causes antidepressant-like effects in adult rodents with no collateral effects. Here, we assessed the effects of a non-effective dose of ketamine in combination with melatonin (KET/MEL), both on neurogenesis as well as on the antidepressant-like effect in mice. Our results showed that KET/MEL combination increased neurogenesis and produced antidepressant-like effects without altering locomotor activity after both single and triple administration protocols. Our data strongly suggest that KET/MEL combination could be used to simultaneously promote neurogenesis, reverting neuronal atrophy and inducing antidepressant-like effects. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
16. Melatonin Rescues the Dendrite Collapse Induced by the Pro-Oxidant Toxin Okadaic Acid in Organotypic Cultures of Rat Hilar Hippocampus.
- Author
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Solís-Chagoyán, Héctor, Domínguez-Alonso, Aline, Valdés-Tovar, Marcela, Argueta, Jesús, Sánchez-Florentino, Zuly A., Calixto, Eduardo, Benítez-King, Gloria, Jembrek, Maja Jazvinšćak, and Šegota, Suzana
- Subjects
MARINE toxins ,MELATONIN ,HIPPOCAMPUS (Brain) ,DENDRITES ,DOMOIC acid ,ALZHEIMER'S disease ,TOXINS ,RATS - Abstract
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. Melatonin, a free-radical scavenger, inhibits tau hyperphosphorylation, modulates phosphatases, and strengthens dendritic arbors. Thus, we determined if OKA alters the dendritic arbors of hilar hippocampal neurons and whether melatonin prevents, counteracts, or reverses these damages. Rat organotypic cultures were incubated with vehicle, OKA, melatonin, and combined treatments with melatonin either before, simultaneously, or after OKA. DNA breaks were assessed by TUNEL assay and nuclei were counterstained with DAPI. Additionally, MAP2 was immunostained to assess the dendritic arbor properties by the Sholl method. In hippocampal hilus, OKA increased DNA fragmentation and reduced the number of MAP2(+) cells, whereas melatonin protected against oxidation and apoptosis. Additionally, OKA decreased the dendritic arbor complexity and melatonin not only counteracted, but also prevented and reversed the dendritic arbor retraction, highlighting its role in post-synaptic domain integrity preservation against neurodegenerative events in hippocampal neurons. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
17. The Timing of Melatonin Administration Is Crucial for Its Antidepressant-Like Effect in Mice.
- Author
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Estrada-Reyes, Rosa, Valdés-Tovar, Marcela, Arrieta-Baez, Daniel, Dorantes-Barrón, Ana María, Quero-Chávez, Daniel, Solís-Chagoyán, Héctor, Argueta, Jesús, Dubocovich, Margarita L., and Benítez-King, Gloria
- Subjects
- *
MELATONIN , *ANTIDEPRESSANTS , *CIRCADIAN rhythms , *PINEAL gland , *ENDOCRINE glands , *PSYCHIATRIC drugs - Abstract
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. However, there is contradictory evidence about the potential antidepressant effect of melatonin itself. Herein we studied melatonin administration in mice at two zeitgeber times (ZT; ZT = 0 lights on; 12:12 L/D), one hour before the beginning (ZT11) and at the middle (ZT18) of the dark phase after either a single or a three-dose protocol. Behavioral despair was assessed through a forced-swimming test (FST) or a tail suspension test (TST), at ZT18.5. A single dose of 4 mg/kg melatonin at ZT11 was effective to reduce the immobility time in both tests. However, acute administration of melatonin at ZT18 was not effective in mice subjected to FST, and a higher dose (16 mg/kg) was required to reduce immobility time in the TST. A three-dose administration protocol of 16 mg/kg melatonin (ZT18, ZT11, and ZT18) significantly reduced immobility time in FST. Data indicate that the timely administration of melatonin could improve its antidepressant-like effect. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
18. Involvement of Melatonin in the Regulation of the Circadian System in Crayfish.
- Author
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Mendoza-Vargas, Leonor, Galicia-Mendoza, Fabiola, Guarneros-Bañuelos, Elizabeth, Báez-Saldaña, Armida, Flores-Soto, Edgar, Fuentes-Pardo, Beatriz, Alvarado, Ramón, Valdés-Tovar, Marcela, Benítez-King, Gloria, Solís-Chagoyán, Héctor, and Sommer, Bettina
- Subjects
MELATONIN ,CRAYFISH ,BIOSYNTHESIS ,BIOLOGICAL evolution ,MITOCHONDRIA - Abstract
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. In these species, information about internal and external time progression might be transmitted by the periodical release of MEL and other endocrine signals acting through the pacemaker. We describe documented and original evidence in support of this hypothesis that also suggests that the rhythmic release of MEL contributes to the reinforcement of the temporal organization of nocturnal or diurnal circadian oscillators. Finally, we discuss how MEL might coordinate functions that converge in the performance of complex behaviors, such as the agonistic responses to establish social dominance status in
Procambarus clarkii and the burrowing behavior in the secondary digging crayfishP. acanthophorus. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
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