Gloria Benítez-King

Instituto Nacional de Psiquiatría, Ciudad de México, The Federal District, Mexico

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Publications (54)183.23 Total impact

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    ABSTRACT: DISC1 (Disrupted-In-Schizophrenia-1) is considered a genetic risk factor for schizophrenia (SZ) and bipolar disorder (BD). DISC1 regulates microtubule stability, migration, and cAMP signaling in mammalian cell lines and mouse brain tissue. cAMP is a regulator of microtubule organization and migration in neurons. Aberrant microtubule organization has been observed in olfactory neuronal precursors (ONP) derived from patients with SZ and BD, which suggests involvement of DISC1 and cAMP. However, the biology of DISC1 in the physiopathology of psychiatric conditions remains elusive. Herein, utilizing ONP obtained from SZ, BD patients and healthy subjects, we have studied DISC1 expression, protein levels, and subcellular distribution by qRT-PCR, immunoblotting, subcellular fractionation, and confocal microscopy. Cell migration and cAMP accumulation were assessed by Transwell and PKA competition assays. We found increased levels of the 75-kDa DISC1 isoform in total cell extracts of ONP from patients with SZ and BD compared with controls. Subcellular distribution showed a significant decrease of cytoplasmic DISC1 concomitant with its augmented levels in transcription sites. Moreover, significant cAMP accumulation and diminished migration were also observed in patients' cells. Alterations of DISC1 levels and its cellular distribution, which negatively modify cAMP homeostasis, microtubule organization, and cell migration, in ONP from patients with SZ and BD, suggest that their presence in early stages of brain development may impact brain maturation and function. © 2015 John Wiley & Sons Ltd.
    CNS Neuroscience & Therapeutics 01/2015; DOI:10.1111/cns.12377 · 4.46 Impact Factor
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    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.
    International Journal of Molecular Sciences 01/2015; 16(1):1907-27. DOI:10.3390/ijms16011907 · 2.46 Impact Factor
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    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.
    Chronobiology International 09/2014; 32(2). DOI:10.3109/07420528.2014.960047 · 2.88 Impact Factor
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    ABSTRACT: El objetivo del presente estudio fue determinar los efectos de 5 mg. de melatonina de liberación inmediata sobre la macro-arquitectura del sueño en ocho pacientes con diagnóstico de Demencia Tipo Alzheimer (DTA) de media a moderada. Utilizando la técnica polisomnográfica (PSG) se realizó un estudio simple ciego, no aleatorio, controlado con placebo. Los registros PSG se llevaron a cabo de la siguiente manera: Noche 1: administración de placebo; noche 2 y 3: administración continua de melatonina (5 mg). Observamos que el tratamiento con melatonina durante la primera noche de administración disminuyó significativamente la latencia de la fase 2, del sueño de ondas delta y el sueño de MOR al ser comparadas con el placebo (P ≤.05). No se observaron diferencias significativas en el tiempo total de cada fase de sueño; tampoco se observaron diferencias en la eficiencia del sueño en presencia de la melatonina. Sin embargo se observó una tendencia a la disminución del tiempo total de vigilia y un aumento del tiempo total de sueño, principalmente durante la segunda noche de tratamiento. Concluimos que la melatonina puede mejorar el sueño en pacientes con DTA de media a moderada.
    Salud Mental 06/2014; 36:271-277. · 0.42 Impact Factor
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    ABSTRACT: El objetivo del presente estudio fue determinar los efectos de 5 mg. de melatonina de liberación inmediata sobre la macro-arquitectura del sueño en ocho pacientes con diagnóstico de Demencia Tipo Alzheimer (DTA) de media a moderada. Utilizando la técnica polisomnográfica (PSG) se realizó un estudio simple ciego, no aleatorio, controlado con placebo. Los registros PSG se llevaron a cabo de la siguiente manera: Noche 1: administración de placebo; noche 2 y 3: administración continua de melatonina (5 mg). Observamos que el tratamiento con melatonina durante la primera noche de administración disminuyó significativamente la latencia de la fase 2, del sueño de ondas delta y el sueño de MOR al ser comparadas con el placebo (P ≤.05). No se observaron diferencias significativas en el tiempo total de cada fase de sueño; tampoco se observaron diferencias en la eficiencia del sueño en presencia de la melatonina. Sin embargo se observó una tendencia a la disminución del tiempo total de vigilia y un aumento del tiempo total de sueño, principalmente durante la segunda noche de tratamiento. Concluimos que la melatonina puede mejorar el sueño en pacientes con DTA de media a moderada.
    Salud Mental 06/2013; 36:271-277. · 0.42 Impact Factor
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    ABSTRACT: Dementias are progressive and neurodegenerative neuropsychiatry 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.
    Salud Mental 05/2013; 36(3):193. · 0.42 Impact Factor
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    ABSTRACT: Olfactory neuroepithelial cells in culture have been proposed as a model to study the physiopathology of psychiatric disorders and biomarker characterization for diagnosis. In patients with schizophrenia (SZ) and bipolar disorder (BD) diminished microtubule-associated proteins expression occurs, which might lead to aberrant microtubular organization and which in turn may affect Ca(2+) voltage-activated currents. The aim of this work was to characterize of microtubule organization as well as of the L-type Ca(2+) current in neuronal precursors obtained from nasal exfoliates of patients with SZ and BD. Microtubule organization was studied by immunofluorescence with a specific anti-III β-tubulin antibody and by quantification of globular and assembled tubulin by Western blot. L-type current recording was performed by whole-cell patch-clamp technique and nifedipine superfusion. The results showed differential altered microtubular organization in neuronal precursors of SZ and BD. Short microtubules were observed in BD neurons, while extensive, unstained subcellular areas and disorganized microtubules were evident in SZ neuronal precursors. Patients with BD showed a decrease in amounts of tubulin in total homogenates and 40% decrease in the globular fraction. However, L-type current in BD was similar to that in healthy subjects (HS). In contrast, this current in SZ was 50% lower. These reduction in L-type current in SZ together with differential microtubule alterations are potential biomarkers that may differentiates SZ and BD.
    Schizophrenia Research 01/2013; 143(2-3). DOI:10.1016/j.schres.2012.11.035 · 4.43 Impact Factor
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    ABSTRACT: The objective of the present study was to evaluate the 5 mg. melatonin effects on the sleep macro-architecture in eight patients with middle to moderate Alzheimer´s disease (DTA). Using the polysomnographic technique (PSG), we made a simple-blind, non-randomized, controlled with placebo study. The PSG was carried out according to the following order: night 1: placebo administration; night 2 and 3: continues melatonin administration. In the first night with melatonin treatment, the sleep latency to the first episode of Stage 2, Delta and REM sleep, was significantly diminished as compared with placebo (≤.05). No significant difference in total time of each sleep stage and sleep efficiency was observed. Nevertheless, a tendency to diminish the total time of nocturnal wake and increase of the total sleep time in the second night with melatonin treatment was observed. We conclude that melatonin can improve sleep in patients with middle to moderate DTA.
    Salud Mental 01/2013; 36(4):271-277. · 0.42 Impact Factor
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    ABSTRACT: Melatonin modulates adult hippocampal neurogenesis in adult mice. Also, plasma melatonin levels and new neuron formation decline during aging probably causing cognitive alterations. In this study, we analyzed the impact of exogenous supplementation with melatonin in three key events of hippocampal neurogenesis during normal aging of mice. The analysis was performed in rodents treated with melatonin during 3, 6, 9 or 12 months. We found an increase in cell proliferation in the dentate gyrus of the hippocampus after 3, 6 and 9 months of treatment (>90%). Additionally, exogenous melatonin promoted survival of new cells in the dentate gyrus (>50%). Moreover, melatonin increased the number of doublecortin-labeled cells after 6 and 9 months of treatment (>150%). In contrast, melatonin administered during 12 months did not induce changes in hippocampal neurogenesis. Our results indicate that melatonin also modulates the neurogenic process in the hippocampus during normal aging of mice. Together, the data support melatonin as one of the positive endogenous regulators of neurogenesis during aging.
    Neuroscience Letters 10/2012; 530(1). DOI:10.1016/j.neulet.2012.09.045 · 2.06 Impact Factor
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    ABSTRACT: La esquizofrenia (EZ) es un trastorno psiquiátrico que se caracteriza por la presencia de delirios, alucinaciones, pensamiento desorganizado, lenguaje desestructurado, alteraciones del comportamiento social y aplanamiento afectivo, entre otros síntomas. Los pacientes con EZ también presentan un déficit en la capacidad olfatoria desde la fase prodrómica del trastorno.
    Salud Mental 06/2012; 35(3):241-246. · 0.42 Impact Factor
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    ABSTRACT: Melatonin concentration in plasma reaches high levels during the night and synchronizes body rhythms with the photoperiod. Previous evidence obtained in cultured cells suggests that melatonin synchronizes cytoskeletal re-arrangements at nocturnal plasma concentration. In this study, we determined the amount of microtubules and microfilaments in the rat hippocampus as an index of cytoskeletal organization in rats submitted to a photoperiodic regime. Additionally, these parameters were determined in control rats, sham rats, pinealectomized rats, and rats that were pinealectomized and treated with melatonin for 1 week. The results showed an increase in both the amount of microfilaments in the hippocampus of rats sacrificed in the dark phase, and in melatonin levels. In addition, a decrease in both microfilament and microtubule amounts occurred in pinealectomized rats. In contrast, melatonin treatment partially reestablished actin and tubulin proportions organized in microfilaments and microtubules, respectively. The results indicate that actin organization in microfilaments was associated with both the photoperiod and with melatonin levels. Together, the data support that cytoskeletal organization is regulated rhythmically by melatonin in synchrony with the photoperiod.
    Neuroscience Letters 03/2012; 511(1):47-51. DOI:10.1016/j.neulet.2012.01.040 · 2.06 Impact Factor
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    ABSTRACT: Neuropsychiatric disorders are characterized by hippocampus decreased volume and loss of dendrite arborizations in the subiculum and prefrontal cortex. These structural changes are associated with diminished memory performance. Hilar neurons of the hippocampus integrate spatial memory and are lost in dementia. They receive information from dentate gyrus neurons through dendrites, while they send axonal tracts to the CA3 region. Dendrites are complex structures of neurons that receive chemical information from presynaptic and postsynaptic terminals. Melatonin, the main product of the pineal gland, has neuroprotective actions through its free radical-scavenging properties and decreases neuronal apoptosis. Recently, we found that melatonin increases dendrite maturation and complexity in new neurons formed in the dentate gyrus of mice. In addition, in N1E-115 cultured cells, the indole stimulates early stages of neurite formation, a process that is known to antecede dendrite formation and maturation. Thus, in this study, we explored whether melatonin stimulates dendrite formation and complexity in the adult rat hippocampus in organotypic slice cultures, which is a model that preserves the hippocampal circuitry and their tridimensional organizations of connectivity. The effects of melatonin were studied in nonpathological conditions and in the absence of harmful agents. The results showed that the indole at nocturnal concentrations reached in the cerebrospinal fluid stimulates dendritogenesis at formation, growth, and maturation stages. Also, data showed that dendrites formed became competent to form presynaptic specializations. Evidence strongly suggests that melatonin may be useful in the treatment of neuropsychiatric diseases to repair the loss of dendrites and re-establish lost synaptic connections.
    Journal of Pineal Research 12/2011; 52(4):427-36. DOI:10.1111/j.1600-079X.2011.00957.x · 7.81 Impact Factor
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    ABSTRACT: Entamoeba histolytica, a protozoan parasite of humans, relays on its striking motility to survive and invade host tissues. Characterization of the molecular components involved in motile processes is crucial to understand its pathogenicity. Although protein components of myosin II hexamers have been predicted from E. histolytica genome data, only a heavy chain of myosin, EhmhcA, has been characterized so far. We have cloned an E. histolytica cDNA sequence that best matched Dictyostelium discoideum myosin essential light chain and found that the cloned sequence is transcribed as an mRNA of 0.445 kb which could encode a protein of 16.88 kDa, within the predicted range for a myosin light chain. In silico analyses revealed that the protein sequence, named EhMLCI, shows two consensus domains for binding MHC, but lacks the N-terminal sequence for actin binding, as in A2 type myosin essential light chains. A single EF-hand calcium-binding domain was identified in the C-terminus and several high score predictability sites for serine and tyrosine phosphorylation. Antibodies to recombinant EhMLCI identified two proteins of approximately 17 and 15 kDa in trophozoite extracts, the latter phophorylated in tyrosines. Serine phosphorylation was not detected. Immunomicroscopy revealed EhMLCI cortical and cytoplasmic distribution in trophozoites and true colocalization with EhmhcA determined by PCC. Co-immunoprecipitation corroborated EhMLCI interaction with EhmhcA. EhMLCI was also localized in actomyosin-containing complexes. Differential partition of phospho-tyrosinated EhMLCI into cell fractions containing the soluble form of EhmhcA and its lack of serine phosphorylation suggest its possible participation in a novel down regulatory mechanism of myosin II activity in E. histolytica.
    Molecular and Biochemical Parasitology 09/2011; 181(1):17-28. DOI:10.1016/j.molbiopara.2011.09.007 · 2.24 Impact Factor
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    ABSTRACT: Brain imaging and histopathological studies suggest that neurodevelopmental anomalies play a key role in the etiology of schizophrenia (SZ) and bipolar disorder (BD). New neuron formation and maturation occur in human olfactory epithelium throughout life. Therefore, the olfactory epithelium has been proposed as a model to study alterations in neurodevelopment, particularly in some psychiatric diseases. However, former studies were done with olfactory epithelium biopsies taken post mortem or under anesthesia from patients with SZ and BD. In this work we have developed a new method to obtain viable neural precursors by exfoliation of the anterior region of the medial lateral turbinate of the nasal cavity from healthy controls, and ambulatory patients. Cells were propagated to establish neural precursor banks. Thawed cells showed cytoskeletal phenotypes typical of developing neurons. They also conserved the ability to differentiate in presence of 2mM dibutyril-cyclic adenosine monophosphate, and maintained voltage-operated Ca(2+) currents in culture. Moreover, proportions of neuronal maturation stages were maintained in cultured exfoliates obtained from SZ and BD patients. Data support that neural precursors obtained from a nasal exfoliate are an excellent experimental model to later approach studies on biomarkers, neural development and cellular alterations in the pathophysiology of SZ and BD.
    Journal of neuroscience methods 07/2011; 201(1):35-45. DOI:10.1016/j.jneumeth.2011.07.009 · 2.30 Impact Factor
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    ABSTRACT: Circadian rhythms are oscillations of physiological functions. The period of their oscillation is about 24 h, and can be synchronized by environmental periodic signals as night–day cycle.
    Salud Mental 04/2011; 34(2):167-173. · 0.42 Impact Factor
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    ABSTRACT: Haloperidol a typical antipsychotic commonly used in the treatment of schizophrenia causes neuronal damage and extrapiramidal symptoms after several years of treatment. These symptoms have been associated with increased levels of oxidative stress. Reactive oxygen species produce cytoskeletal collapse and an excessive phosphorylation of tau, a microtubule-associated protein that plays a key role in microtubule stabilization, and in growth cone and neurite formation, which are cytoskeletal phenotypes that participate in neurodevelopment. Thus, we hypothesized that haloperidol produces neurocytoskeletal disorganization by increasing free radicals and tau hyperphosphorylation, and consequently, the loss of neurodevelopmental cytoskeletal phenotypes, neurites and growth cones. The purpose of this work was the characterization of neuronal cytoskeletal changes caused by haloperidol in neuroblastoma N1E-115 cells. We also studied the mechanisms by which haloperidol causes cytoskeletal changes. The results showed that haloperidol at 100microM caused a complete cytoskeleton collapse in the majority of the cells. Melatonin, a free radical scavenger, blocks tau hyperphosphorylation, and microtubule disorganization caused by haloperidol in a dose-response mode. Additionally, the indole blocks lipoperoxide formation in haloperidol treated cells. The results indicate that free radicals and tau hyperphosphorylation produced by haloperidol caused a cytoskeletal collapse and the lost of growth cones and neurites. These effects were blocked by melatonin. Data suggest that extrapiramidal symptoms in schizophrenic patients can be produced by cytoskeletal disorganization during adult brain neurodevelopment after prolonged haloperidol treatment that can be prevented by melatonin.
    European journal of pharmacology 10/2010; 644(1-3):24-31. DOI:10.1016/j.ejphar.2010.06.057 · 2.59 Impact Factor
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    ABSTRACT: In the course of adult hippocampal neurogenesis, the postmitotic maturation and survival phase is associated with dendrite maturation. Melatonin modulates the survival of new neurons with relative specificity. During this phase, the new neurons express microtubule-associated protein doublecortin (DCX). Here, we show that the entire population of cells expressing DCX is increased after 14 days of treatment with melatonin. As melatonin also affects microtubule polymerization which is important for neuritogenesis and dendritogenesis, we studied the consequences of chronic melatonin administration on dendrite maturation of DCX-positive cells. Treatment with melatonin increased the number of DCX-positive immature neurons with more complex dendrites. Sholl analysis revealed that melatonin treatment lead to greater complexity of the dendritic tree. In addition, melatonin increased the total volume of the granular cell layer. Besides its survival-promoting effect, melatonin thus also increases dendritic maturation in adult neurogenesis. This might open the opportunity of using melatonin as an adjuvant in attempts to extrinsically stimulate adult hippocampal neurogenesis in neuropsychiatric disease, dementia or cognitive ageing.
    Journal of Pineal Research 09/2010; 50(1):29-37. DOI:10.1111/j.1600-079X.2010.00802.x · 7.81 Impact Factor
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    ABSTRACT: Retinular photoreceptors are structures involved in the expression and synchronization of the circadian rhythm of sensitivity to light in crayfish. To determine whether melatonin possesses a differential effect upon the receptor potential (RP) amplitude of retinular photoreceptors circadian time (CT)-dependent, we conducted experiments by means of applying melatonin every 2h during a 24-hour cycle. Melatonin with 100 nM increased RP amplitude during subjective day to a greater degree than during subjective night. To determine whether MT(2) melatonin receptors regulate the melatonin-produced effect, we carried out two experiments, circadian times (CTs) 6 and 18, which included the following: (1) application of the MT(2) receptor selective agonist 8-M-PDOT and antagonist DH97, and (2) the specific binding of [(125)I]-melatonin in eyestalk membranes. The amount of 10 nM of 8-M-PDOT increased RP amplitude in a similar manner to melatonin, and 1 nM DH97 abolished the increase produced by melatonin and 8-M-PDOT. Binding of [(125)I]-melatonin was saturable and specific. Scatchard analysis revealed an affinity constant (K(d)) of 1.1 nM and a total number of binding sites (B(max)) of 6 fmol/mg protein at CT 6, and a K(d) of 1.46 nM and B(max) of 7 fmol/mg protein at CT 18. Our results indicate that melatonin increased RP amplitude of crayfish retinular photoreceptors through MT(2)-like melatonin receptors. These data support the idea that melatonin is a signal of darkness for the circadian system in crayfish retinular cells.
    Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 09/2009; 154(4):486-92. DOI:10.1016/j.cbpa.2009.07.025 · 2.20 Impact Factor
  • G Benítez-King, E Soto-Vega, G Ramírez-Rodriguez
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    ABSTRACT: Cell migration and adhesion are cytoskeleton- dependent functions that play a key role in epithelial physiology. Specialized epithelial cells in water transport have specific microfilament rearrangements that make these cells adopt a polyhedral shape, forming a sealed monolayer which functions as permeability barrier. Also, specific polarized microfilament phenotypes are formed at the front and the rear of migratory epithelial cells. In pathological processes such as cancer, increased migration occurs in invasive cells driven by the formation of polarized and differential microfilament phenotypes. Melatonin, the main product secreted by the pineal gland during dark phase of the photoperiod, acts as a cytoskeletal modulator in normal and cancer cells. In this paper we will summarize evidence supporting that melatonin acts as a microfilament modulator in epithelial MDCK cells, and we will describe its effects on cytoskeleton organization involved in the mechanism by which melatonin synchronizes water transport. In addition, we will review recent data that indicate that melatonin is able to switch microfilament phenotypes in MCF-7 human mammary cancer cells, from invasive migratory cells to dormant microfilament phenotypes that occur in non- migratory cells. Moreover, we will discuss the implications of the cytoskeleton as therapeutic target for cancer cells.
    Histology and histopathology 07/2009; 24(6):789-99. · 2.24 Impact Factor
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    ABSTRACT: Regulation of adult hippocampal neurogenesis is influenced by circadian rhythm, affected by the manipulation of sleep, and is disturbed in animal models of affective disorders. These observations and the link between dysregulation of the circadian production of melatonin and neuropsychiatric disorders prompted us to investigate the potential role of melatonin in controlling adult hippocampal neurogenesis. In vitro, melatonin increased the number of new neurons derived from adult hippocampal neural precursor cells in vitro by promoting cell survival. This effect was partially dependent on the activation of melatonin receptors as it could be blocked by the application of receptor antagonist luzindole. There was no effect of melatonin on cell proliferation. Similarly, in the dentate gyrus of adult C57BL/6 mice in vivo, exogenous melatonin (8 mg/kg) also increased the survival of neuronal progenitor cells and post-mitotic immature neurons. Melatonin did not affect precursor cell proliferation in vivo and also did not influence neuronal and glial cell maturation. Moreover, melatonin showed antidepressant-like effects in the Porsolt forced swim test. These results indicate that melatonin through its receptor can modulate the survival of newborn neurons in the adult hippocampus, making it the first known exogenously applicable substance with such specificity.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 06/2009; 34(9):2180-91. DOI:10.1038/npp.2009.46 · 8.68 Impact Factor