Lab. Intercelular Communication Dept. Physiology Faculty of Medicine National Autonomous University of Mexico Av. Universidad 3000 Mexico 04510 D. F. Mexico Phone & Fax: +52 -5 6232348
Joined to the Department of Physiology at the Medical School, UNAM as an associate professor in the group of Prof. René Drucker-Colín in January 1994. She was born in Beijing, China and studied in the 2nd Military University of Medicine (Shanghai), University of Beijing and Medical School, UNAM (as part of a Cultural Exchange Programme). She received MD (1985), MSc (1988) and DSc (1992) in the UNAM, where she worked on Neurophysiology and Theoretical Biology under directions of Prof. Francisco Alonso de Florida, Dr. Eugenio Martínez-Uriegas and Dr. Raúl Aguilar Roblero. External research trainings include postdoctoral stay in Prof. Philip Maini's group at Centre of Mathematical Biology, University of Oxford (1992 - 1993), sabbatical leave in Prof. Peter Somogyi FRS group at MRC Anatomical Neuropharmacology Unit, University of Oxford, as an IBRO research fellow (2000 - 2001), research fellow (2007-2008) and research sojourns in the Dept. Of Cell Physiology, Max Planck Institute for Medical Research, Heidelberg (2003) and Oxford (2009) . She has taught Human Physiology and Fundamental Neurophysiology for both undergraduate and graduate students. In 2002, she was elected as a member of Mexican Academy of Science.
Abstract: 2-Deoxy-D-glucose (2-DG) administration causes transient depletion of glucose derivates and ATP. Hence, it can be used in a model system to study the effects of a mild glycoprivic brain insult mimicking transient hypoglycemia, which often occurs when insulin or oral hypoglycemic agents are administered for diabetes control. In the present study, the effect of a single 2-DG application (500mg/kg, a clinically applicable dose) on glial reactivity and neurogenesis in adult rat hippocampus was examined, as well as a possible temporal correlation between these two phenomena. Post-insult (PI) glial reactivity time course was assessed by immunoreaction against glial fibrillary acidic protein (GFAP) during the following 5 consecutive days. A clear increase of GFAP immunoreactivity in hilus was observed from 48 to 96h PI. Moreover, enhanced labeling of long radial processes in the granule cell layer adjacent to hilus was evidenced. On the other hand, a transient increase of progenitor cell proliferation was detected in the subgranular zone, prominently at 48h PI, coinciding with the temporal peak of glial activation. This increase resulted in an augment of immature neuroblasts double labeled with 5-bromo-deoxyuridine (BrdU) and with double cortin (DCX) at day 7 PI. Around half of these cells survived 28 days showing matured neuronal phenotype double labeled by BrdU and a neuronal specific nuclear protein marker (NeuN). These findings suggest that a transient neuroglycoprivic state exerts a short-term effect on glial activation that possibly triggers a long-term effect on neurogenesis in hippocampus.
Abstract: We have previously reported that dietary tryptophan (TRP) restriction in a rat crucial postnatal developmental stage induces depression-like behavior and alters dendritic spine density in CA1 pyramidal neurons and granule cells of the hippocampus. Due to astrocyte involvement in critical brain mechanisms, it seems worth to investigate possible adaptive changes in the glial population with TRP restriction. Experimental rats were fed with low TRP diet (20% of TRP level of the laboratory rat chow) from postnatal days 30-60. Antibody against glial fibrillary acidic protein (GFAP), a principal intermediate filament in astrocytes, was used to evaluate cytoskeletal hypertrophy and glial proliferation. Our results showed an increase in size and branching of GFAP-immunoreactive (IR) cells in the dorsal hippocampus and amygdala, characteristics of an astrocytic activation. No significant differences were found regarding the number of GFAP-IR cells in both regions. These results indicate that dietary TRP restriction can induce astrocytic activation, hence, provide further evidences supporting the hypothesis that serotonin may also modulate glial morphology.
Abstract: Given the evidence that maternal hyperthyroidism (MH) compromises expression of neuronal cytoskeletal proteins in the late fetal brain by accelerated neuronal differentiation, we investigated possible consequences of MH for the emotional and cognitive functions of adult offspring during acute and subchronic stress coping. Experimental groups consisted of male rat offspring from mothers implanted with osmotic minipumps infusing either thyroxine (MH) or vehicle (Ctrl) during pregnancy. Body weight and T4 level were monitored during the first 3 postnatal months, and no differences were found with the controls. We analyzed hippocampal CA3 pyramidal neurons and dentate granular cell morphology during several postnatal stages and found increased dendritic arborization. On postnatal day 90 a modified subchronic mild stress (SCMS) protocol was applied to experimental subjects for 10 days. The Morris water maze was used before, during, and after application of the SCMS protocol to measure spatial learning. The tail suspension test (TST) and forced-swimming test (FST) were used to evaluate behavioral despair. The MH rats displayed normal locomotor activity and spatial memory prior to SCMS, but impaired spatial learning after acute and chronic stress. In both the FST and TST we found that MH rats spent significantly more time immobile than did controls. Serum corticosterone level was found to increase after 30 min of restraint stress, and corticotropin-releasing factor immunoreactivity was found to be increased in the central nucleus of the amygdala. Our results suggest that MH in rats leads to the offspring being more vulnerable to stress in adulthood.
Abstract: By the time an organism is in an embryonary stage, neurons must recognize and establish specific connections with other neurons or tissues in order to maintain an appropriate functioning of the nervous system. Since a neural network consists of lots of neurons, finding the correct pathway for each one of them clearly constitutes a problem
of morphogenesis. In this article we present this problem experimentally and construct a theoretical model to explain the experimental results, as well. Numerical simulations reproduce the observations and allow to predict the existence and functioning of chemicals in the nervous system, which act as a guide in the neurite growth and connections.
Abstract: Serotonin transmission dysfunction has been suggested to play an important role in depression and anxiety. This study reports the results of a series of experiments in which rats were subjected to extended maize-based tortilla diets during early postnatal stages. This diet contains only approximately 20% of the L-tryptophan in normal diets of laboratory rodents. Compared with controls, experimental rats displayed a significant increase of immobility counts in the forced swimming test and exhibited anxiety-like behavior in the elevated plus maze test after 1 month of diet treatment. Low levels of serotonin contents were found in prefrontal cortex, striatum, hippocampus, and brainstem using high-performance liquid chromatography. Immunocytochemical reactions against 5-Bromo-2'-deoxyuridine revealed a significant decrease in the proliferation rate for the subgranular zone of dentate gyrus. c-Fos expression after the forced swimming test was found reduced in prefrontal cortex, dentate gyrus, CA1, and hilus of hippocampus and amygdala. Moreover, dendrite arbor atrophy and decreased spine density were evident in Golgi-Cox-impregnated CA1 pyramidal neurons. Abnormal dendrite swelling in dentate gyrus granule cells was also observed. These findings indicate an involvement of hyposerotoninergia in emotional disturbance produced by L-tryptophan restriction during critical developmental stages and suggest that neuroplasticity changes might underlie these changes.
Abstract: Adrenal chromaffin cell (ACC) transplants, alone or combined with levodopa treatment, were used in attempted therapy for Parkinson's disease (PD). In a previous study, we demonstrated that levodopa caused chromaffin cell death either by necrosis or by apoptosis in cell culture. Here we report the beneficial effect of a water-soluble derivative of fullerene C(60) (a novel molecule with potent antioxidant properties) and of ascorbic acid when applied to chromaffin cell cultures exposed to levodopa. Both antioxidants remarkably increase the ACC survival and prevent cell death, including apoptosis. Although ACC transplants are not currently considered as an option for PD treatment, these observations should help in exploring the possibilities of preventing the neurotoxicity generated by levodopa and in envisaging new strategies for PD treatment by combining the clinical use of levodopa and potent antioxidants. Chemical properties of fullerene related to biological uses are discussed.
Abstract: Synapses exhibit different short-term plasticity patterns and this behaviour influences information processing in neuronal networks. We tested how the short-term plasticity of excitatory postsynaptic currents (EPSCs) depends on the postsynaptic cell type, identified by axonal arborizations and molecular markers in the hippocampal CA1 area. Three distinct types of short-term synaptic behaviour (facilitating, depressing and combined facilitating-depressing) were defined by fitting a dynamic neurotransmission model to the data. Approximately 75 % of the oriens-lacunosum-moleculare (O-LM) interneurones received facilitating EPSCs, but in three of 12 O-LM cells EPSCs also showed significant depression. Over 90 % of the O-LM cells were immunopositive for somatostatin and mGluR1alpha and all tested cells were decorated by strongly mGluR7a positive axon terminals. Responses in eight of 12 basket cells were described well with a model involving only depression, but the other cells displayed combined facilitating-depressing EPSCs. No apparent difference was found between the plasticity of EPSCs in cholecystokinin- or parvalbumin-containing basket cells. In oriens-bistratified cells (O-Bi), two of nine cells showed facilitating EPSCs, another two depressing, and the remaining five cells combined facilitating-depressing EPSCs. Seven of 10 cells tested for somatostatin were immunopositive, but mGluR1alpha was detectable only in two of 11 tested cells. Furthermore, most O-Bi cells projected to the CA3 area and the subiculum, as well as outside the hippocampal formation. Postsynaptic responses to action potentials recorded in vivo from a CA1 place cell were modelled, and revealed great differences between and within cell types. Our results demonstrate that the short-term plasticity of EPSCs is cell type dependent, but with significant heterogeneity within all three interneurone populations.
Abstract: It is well known that simple reaction-diffusion systems can display very rich pattern formation behaviour. Here we have studied two examples of such systems in three dimensions. First we investigate the morphology and stability of a generic Turing system in three dimensions and then the well-known Gray-Scott model. In the latter case, we added a small number of morphogen sources in the system in order to study its robustness and the formation of connections between the sources. Our results raise the question of whether Turing patterning can produce an inductive signalling mechanism for neuronal growth. (C) 2002 Elsevier Science B.V. All rights reserved.
Abstract: The results reported herein address the question of synaptogenesis between adrenal chromaffin cells and striatal neurons. The release of dopamine from chromaffin cells in the presence of striatal neurons was also examined. Co-culture of newborn rat chromaffin cells and striatal neurons at 1:1 ratio was made. Cultures were examined morphologically using immunocytochemistry and ultrastructural techniques (transmission electron microscopy), while quantitation of dopamine in the culture media by HPLC-ECD was also determined. Neurite outgrowth from chromaffin cells was enhanced in the presence of striatal neurons and numerous synaptic-like contacts between these two cell types were observed. Higher concentration of dopamine was also present in the co-culture medium as compared with those containing only chromaffin cells. The development of synapses between these two types of cells may give support to the functionality of transplants in human cases of Parkinson disease (PD).
Abstract: Adrenal chromaffin cell (ACC) transplantation has been considered as one of the therapeutic strategies for Parkinson disease (PD). This strategy involves the administration of L-DOPA, although in reduced doses, to ACC-transplanted patients. Using cytochemical and morphological methods, we examined the effects of clinically applicable concentrations of L-DOPA on cultured chromaffin cells. We found an increase of cell death in both necrotic and apoptotic patterns. These data suggest that therapeutic preventive measures during ACC transplantation processes for PD should be taken.
Abstract: The ability of C-60 to affect guinea pig myocyte electrical activity and rat chromaffin cell differentiation and proliferation was examined in vitro. C-60 was dissolved with polyvinylpyrrolidone (PVP) in physiological solutions and short-term and subchronic application were carried out. No significant effects on electrical activity of isolated myocytes by short-term extracellular application and chromaffin cell differentiation and proliferation by subchronic application of C-60 + PVP were observed. Possible therapeutic applications of this compound are discussed.
Abstract: Ensembles of mutually coupled ultradian cellular oscillators have been proposed by a number of authors to explain the generation of circadian rhythms in mammals. Most mathematical models using many coupled oscillators predict that the output period should vary as the square root of the number of participating units, thus being inconsistent with the well-established experimental result that ablation of substantial parts of the suprachiasmatic nuclei (SCN), the main circadian pacemaker in mammals, does not eliminate the overt circadian functions, which show no changes in the phases or periods of the rhythms. From these observations, we have developed a theoretical model that exhibits the robustness of the circadian clock to changes in the number of cells in the SCN, and that is readily adaptable to include the successful features of other known models of circadian regulation, such as the phase response curves and light resetting of the phase.
Abstract: We report the use of an extremely low frequency magnetic field (ELF-MF, 60 Hz, 10 Grms) to stimulate cultured chromaffin cells to determine the possible changes that may occur in their electrical properties. The results showed that ELF-MF not only facilitated neurite outgrowth, but also formation of neurite varicosity with high concentration of catecholamines. This report also shows for the first time that a greater number of cultured chromaffin cells differentiated by ELF-MF have spontaneous extracellular electrical activity and that their firing frequency is higher than that seen in non-stimulated cells.
Abstract: In order to test the hypothesis that each side of the suprachiasmatic nuclei (SCN) contains independent circadian oscillators, pairs of cells were recorded from contralateral SCN alternating each nucleus, in hypothalamic slices prepared for extracellular single unit recording. The analysis was made by separating the data from right and left nuclei. Circadian variations in the electrical activity of neurones were present in either side of the SCN. The right SCN presented a bimodal waveform, without apparent change of phase between slices prepared from animals under LD or DD. In contrast, the fluctuations of the left SCN were unimodal in slices of both groups. There was also a difference of 2 h in the interval of maximal activity between the groups from LD and DD. These asymmetrical wave forms are consistent with previous studies suggesting that the contralateral SCN may act as independent oscillators.
Abstract: The suprachiasmatic nucleus (SCN) is believed to contain the main generator of circadian rhythmicity in mammals. In order to obtain further functional details of this, electrophysiological extracellular measurements in vitro were made. By means of an interspike interval distribution analysis, it is shown that there is a novel kind of neuronal firing pattern: the harmonic pattern. From these observations, we have developed a theoretical model based on possible filtering processes occurring during synaptic transmission. The model suffices to infer that regular ultradian oscillators could be an emergent property of circuit interactions of cells in the suprachiasmatic nucleus.
Abstract: Suprachiasmatic nucleus contains the main circadian pacemaker for mammals rhythmical behavior and physiology. In this paper we revise recent experimental advances on electrophysiological studies to suprachiasmatic circadian pacemaker in rodents. Our growing understanding of the electrophysiology of this nucleus will help to elucidate the clock organization and its input and output mechanisms.
Abstract: Electrophysiological studies of neurons in the suprachiasmatic nucleus, of rat brain slices in vitro, reveal characteristic firing patterns which have been previously classified as regular, irregular and bursting. A new kind of neuronal firing is found, by means of an interspike interval distribution analysis. Based on these results a new classification scheme is suggested. A model to explain the presence of all the experimental patterns is delivered. The model not only suffices to infer the presence of regular oscillators, but also suggests interesting consequences concerning the components of the circadian system and their statistical behavior.
