Scielo RSS <![CDATA[Biological Research]]> vol. 38 num. 4 lang. en <![CDATA[SciELO Logo]]> <![CDATA[Patricio Zapata OrmeƱo,<b> <strong>semblanza de un maestro</strong></b>]]> <![CDATA[How the carotid body works: Different strategies and preparations to solve different problems]]> This is a review of the different experimental approaches developed to solve the problems in our progress towards a comprehensive understanding of how arterial chemoreceptors operate. An analysis is performed of the bases, advantages and limits of the following preparations: studies of ventilatory reflexes originated from carotid bodies (CBs) in the entire animal; recordings of CB chemosensory discharges in situ; CB preparations perfused in situ; CB explants in oculo; CB explants in ovo; CB preparations incubated in vitro; CB preparations superfused in vitro; CB preparations perfused and superfused in vitro; CB tissue slices in vitro; cells acutely dissociated from CBs; CB cells in tissue culture; petrosal ganglia superfused in vitro; petrosal ganglion cells in tissue culture; and co-cultures of CB and sensory ganglion cells. A brief historical account is given of the passage from one preparation to the next one. Emphasis is placed on personal experience with the different preparations whenever possible. Examples are given of the importance of selecting the appropriate experimental preparation for solving each particular theoretical problem. In fact, brilliant ideas on how the CB works have been unproductive until finding the adequate experimental approach to explore the validity of such ideas. <![CDATA[Electrophysiological properties of rat nodose ganglion neurons co-transplanted with carotid bodies into the chick chorioallantoic membrane]]> The electrophysiological properties of nodose ganglion neurons were evaluated immediately after removing nodose ganglia from young adult rats and 3 to 10 days after nodose ganglia implantation _either alone or co-implanted with carotid bodies_ onto the chick chorioallantoic membrane. Implanted and co-implanted nodose neurons were less excitable than acutely recorded nodose neurons. Co-implanted neurons also showed reduced amplitudes for both action potentials and spike after-hyperpolarizations relative to those found in acutely recorded nodose ganglion neurons and a smaller time constant (τ) than that found in implanted neurons. In addition, no spontaneous activity was recorded from nodose ganglion neurons co-implanted with carotid bodies during 3-9 days, which suggests that functional synapses between carotid glomus cells and nodose neurons were not yet established. Results indicate the feasibility of obtaining viable nodose neurons for up to 10 days grafted onto the chick chorioallantoic membrane, where they can conserve most of their passive and active membrane properties and also are susceptible to carotid bodies trophic influences. They also suggest that nodose neurons would need more time for the development of functional synapses when grafted with carotid body glomus cells. <![CDATA[Cardiovascular and ventilatory acclimatization induced by chronic intermittent hypoxia: A role for the carotid body in the pathophysiology of sleep apnea]]> Patients with obstructive sleep apnea (OSA) show augmented ventilatory, sympathetic and cardiovascular responses to hypoxia. The facilitatory effect of chronic intermittent hypoxia (CIH) on the hypoxic ventilatory response has been attributed to a potentiation of the carotid body (CB) chemosensory response to hypoxia. However, it is a matter of debate whether the effects induced by CIH on ventilatory responses to hypoxia are due to an enhanced CB activity. Recently, we studied the effects of short cyclic hypoxic episodes on cat cardiorespiratory reflexes, heart rate variability, and CB chemosensory activity. Cats were exposed to cyclic hypoxic episodes repeated during 8 hours for 4 days. Our results showed that CIH selectively enhanced ventilatory and carotid chemosensory responses to acute hypoxia. Exposure to CIH did not increase basal arterial pressure, heart rate, or their changes induced by acute hypoxia. However, the spectral analysis of heart rate variability of CIH cats showed a marked increase of the low/high frequency ratio and an increased variability in the low frequency band of heart rate variability, similar to what is observed in OSA patients. Thus, it is likely that the enhanced CB reactivity to hypoxia may contribute to the augmented ventilatory response to hypoxia. <![CDATA[<strong>Chemical and electric transmission in the carotid body chemoreceptor complex </strong>]]> Carotid body chemoreceptors are complex secondary receptors. There are chemical and electric connections between glomus cells (GC/GC) and between glomus cells and carotid nerve endings (GC/NE). Chemical secretion of glomus cells is accompanied by GC/GC uncoupling. Chemical GC/NE transmission is facilitated by concomitant electric coupling. Chronic hypoxia reduces GC/GC coupling but increases G/NE coupling. Therefore, carotid body chemoreceptors use chemical and electric transmission mechanisms to trigger and change the sensory discharge in the carotid nerve. <![CDATA[<strong>Central actions of somatostatin in the generation and control of breathing </strong>]]> The neuropeptide somatostatin is involved in many functions in the central nervous system as well as in the periphery. When it is centrally injected, an irreversible apnea is often developed. In the present review, we discuss the effects of somatostatin as the result of its actions at three levels of the respiratory neural network: a) by modulating the output of cranial or spinal motoneurons; b) by altering the genesis of the respiratory rhythm in the brainstem; and c) by regulating the chemosensory drive input into the respiratory pattern generator <![CDATA[<strong>Effect of 0.25 ppm Ozone exposure on pulmonary damage induced by bleomycin</strong>]]> To study the effect of ozone in a chronically damaged lung, we used a bleomycin (BLM) induced pulmonary fibrosis model. Both endotracheal instillation of BLM and O3 exposure both produce lung inflammation and fibrosis. Oxidative stress would be a common mechanism of damage for both BLM and O3. Our aim was to assess lung injury induced by 5 and 60 days of intermittent exposure to 0.25 ppm O3 in rats with bleomycin-induced pulmonary fibrosis. Thirty-day-old Sprague Dawley rats were endotracheally instilled with BLM (1 U/100 g body weight) and, 30 days later, exposed to 0.25 ppm O3 (0.25 ppm 4 h per day, 5 days a week). Histopatology controls were instilled with saline and breathing room air. Histopathological evaluation of lungs was done 5 and 60 days after O3 exposure. BLM-induced lung damage did not change after 60 days of intermittent O3 exposure. Five days of O3 exposure increased the mean score of BLM-induced pulmonary inflammation and fibrosis (p=0.06). Frequency of bronchopneumonia increased from 1/7 to 6/6 (p <0.001), suggesting that a short-term exposure to O3 in a previously damaged lung might be a risk factor for developing further lung injury <![CDATA[The 'whole-animal approach' as a heuristic principle in neuroscience research]]> Neuroscience embraces a heterogeneous group of disciplines. A conceptual framework that allows a better articulation of these different theoretical and experimental perspectives is needed. A `whole-animal approach' is proposed as a theoretical and hermeneutic tool. To illustrate the potential of this point of view, an overview of the research that has been performed in the extinction of fear-conditioned responses from Pavlov to the present is discussed. This is an example of how a whole-animal-based approach may help to organize and integrate basic and clinical neuroscience research. Our proposal is in agreement with recent statements calling for more integrative approaches in biological and neuropsychiatric research <![CDATA[Local regulation of the axonal phenotype, a case of merotrophism]]> In this essay, we show that several anatomical features of the axon, namely, microtubular content, caliber and extension of sprouts, correlate on a local basis with the particular condition of the glial cell, i.e., the anatomy of axons is dynamic, although it is seen usually in its `normal' state. The occurrence of ribosomes and messenger RNAs in the axon suggests that axoplasmic proteins are most likely synthesized locally, at variance with the accepted notion that they are supplied by the cell body. We propose that the supporting cell (oligodendrocyte or Schwann cell) regulates the axonal phenotype by fine-tuning the ongoing axonal protein synthesis. <![CDATA[<strong>Cell surface and gene expression regulation molecules in dystrophinopathy</strong>: <strong><i>mdx</i></strong><strong> vs. Duchenne</strong>]]> Duchenne muscular dystrophy (DMD) is secondary to loss-of-function mutations in the dystrophin gene. The causes underlying the progression of DMD, differential muscle involvement, and the discrepancies in phenotypes among species with the same genetic defect are not understood. The mdx mouse, an animal model with dystrophin mutation, has a milder phenotype. This article reviews the available information on expression of signaling-related molecules in DMD and mdx. Extracellular matrix proteoglycans, growth factors, integrins, caveolin-3, and neuronal nitric oxide synthase expression do not show significant differences. Calcineurin is inconsistently activated in mdx, which is associated with lack of cardiomyopathy, compared to the permanent calcineurin activation in mdx/utrophin null mice that have a DMD-like cardiomyopathy. Levels of focal adhesion kinase (FAK) and extracellular regulated kinases (ERKs) differ among mdx and DMD. Further work is needed to identify the point of discrepancy in these signaling molecules' pathways in dystrophynopathies. <![CDATA[<strong>Oligodendrocytes damage in Alzheimer's disease</strong>: <strong>Beta amyloid toxicity and inflammation</strong>]]> Research on Alzheimer's disease (AD) focuses mainly on neuronal death and synaptic impairment induced by β-Amyloid peptide (Aβ), events at least partially mediated by astrocyte and microglia activation. However, substantial white matter damage and its consequences on brain function warrant the study of oligodendrocytes participation in the pathogenesis and progression of AD. Here, we analyze reports on oligodendrocytes' compromise in AD and discuss some experimental data indicative of Aβ toxicity in culture. We observed that 1 μM of fibrilogenic Aβ peptide damages oligodendrocytes in vitro; while pro-inflammatory molecules (1 μg/ml LPS + 1 ng/ml IFNγ) or the presence of astrocytes reduced the Ab-induced damage. This agrees with our previous results showing an astrocyte-mediated protective effect over Aβ-induced damage on hippocampal cells and modulation of the activation of microglial cells in culture. Oligodendrocytes protection by astrocytes could be, either by reduction of Aβ fibrilogenesis/deposition or prevention of oxidative damage. Likewise, the decrease of Aβ-induced damage by proinflammatory molecules could reflect the production of trophic factors by activated oligodendrocytes and/or a metabolic activation as observed during myelination. Considering the association of inflammation with neurodegenerative diseases, oligodendrocytes impairment in AD patients could potentiate cell damage under pathological conditions.