The accessory olfactory bulb (AOB) in the adult rat is organized into external (ECL) and internal (ICL) cellular layers separated by the lateral olfactory tract (LOT). The most superficial layer, or vomeronasal nerve layer, is composed of two fiber contingents that distribute in rostral and caudal halves. The second layer, or glomerular layer, is also divided by a conspicuous invagination of the neuropil of the ECL at the junction of the rostral and caudal halves. The ECL contains eight cell types distributed in three areas: a subglomerular area containing juxtaglomerular and superficial short-axon neurons, an intermediate area harboring large principal cells (LPC), or mitral and tufted cells, and a deep area containing dwarf, external granule, polygonal, and round projecting cells. The ICL contains two neuron types: internal granule (IGC) and main accessory cells (MACs). The dendrites and axons of LPCs in the two AOB halves are organized symmetrically with respect to an anatomical plane called linea alba. The LPC axon collaterals may recruit adjacent intrinsic, possibly gamma-aminobutyric acid (GABA)-ergic, neurons that, in turn, interact with the dendrites of the adjacent LPCs. These modules may underlie the process of decoding pheromonal clues. The most rostral ICL contains another neuron group termed interstitial neurons of the bulbi (INBs) that includes both intrinsic and projecting neurons. MACs and INBs share inputs from fiber efferents arising in the main olfactory bulb (MOB) and AOB and send axons to IGCs. Because IGCs are a well-known source of modulatory inputs to LPCs, both MACs and INBs represent a site of convergence of the MOB with the AOB.
SUMMARYA mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-a (TNF-a), interleukin-1a (IL-1a) and transforming growth factor-b ( TGF-b). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-a and IL-1a immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-a and IL-1a were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-a and IL-1a as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-b production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-a and IL-1a production that coincided with the highest level of TGF-b. The bacillary counts were highest as the macrophages became large, vacuolated foamy cells, and containing numerous bacilli with immunoreactivity to mycobacterial lipids and lipoarabinomannan ( LAM). These macrophages displayed poor and scarce TNF-a and IL-1a immunostaining but still strong immunoreactivity to TGF-b. These cytokine production kinetics and the spatial relationship between immunostained cells and lung lesions corroborate the important role of TNF-a and IL1a in the constitution of granulomas and immune protection during the early phase of the infection, and also suggest an important if not primary role for TGF-b in the immunopathogenesis of the advanced forms of pulmonary tuberculosis.
The oval nucleus (Ov) of the bed nuclei of the stria terminalis was studied in adult rats. The Ov is composed of 11 neuron types distributed into a shell and a core domain. The stria terminalis, internal capsule, ventral amygdaloid pathway, and medial forebrain bundle are the main sources of afferents to the neuropil of the Ov. The nucleus shell contains abundant intrinsic neurons possibly connected among themselves and with the core by centripetal axon collaterals. Series of intrinsic neurons in the shell, linked with both short-axon and projecting neurons in the core, suggest a centripetal control of projecting neurons. In situ hybidization for vesicular glutamate transporter (VGlu) and glutamic acid decarboxylase (GAD) show numerous GAD-synthesizing neurons and an absence of VGlu-synthesizing neurons. In the electron microscope, the neuropil of the Ov contains axospinous, axoshaft, axosomatic, mixed (i.e., chemical-electrical), and axoaxonic synapses, in order of frequency. Synaptic boutons in apposition with the initial segment, represent an additional axoaxonic interaction. Further neural synchronization of the Ov occurs via gap junctions between somata, soma-dendrite, and possibly by apposition between axon terminals. The putative inputs from the major tracts of the forebrain coupled with the cytological organization of the Ov make it one of the most complex structures of the mammalian brain.
This study unravels the microscopic organization of the juxtacapsular nucleus of the bed nuclei of the stria terminalis (Ju) by using silver impregnation and electron microscopic techniques. Examination of Golgi-impregnated specimens demonstrates that the Ju has precise boundaries primarily determined by a conical condensation of fibers of the stria terminalis (StT) around the nucleus. The internal capsule, ansa peduncularis, and medial forebrain bundle together with the StT provide extrinsic afferents to the neuropil of the Ju. Two main neuron types are found in the Ju: interneurons (including basket and neurogliaform cells) and projection neurons (bipolar and small pyramidal cells). The bipolar cell type accounts for about 80% of the sampled neurons. Short-axon neurons located within the dorsal part of the Ju send descending fibers that appear to terminate on the bipolar neurons, suggesting the existence of vertically oriented functional units within the nucleus. With the electron microscope, Ju neurons are seen in clusters of two or three neurons coupled by gap junctions. The neuropil contains numerous dendrites, axons, myelinated axons, and several types of synaptic interactions, including axospinous, axoshaft, and axosomatic. Within the neuropil, Ju neurons appear to be presynaptically modulated by axoaxonal interactions. The present findings suggest a model wherein bipolar neurons represent the output system of the Ju controlled by the interneurons, which would, in turn, be modulated by collaterals arising from the tributary fiber tracts. Additional neural interaction between Ju neurons utilizes gap junction-mediated electrotonic coupling.
The continuous production and addition of new neurons during life in the olfactory bulb is well accepted and has been extensively studied in rodents. This process could allow the animals to adapt to a changing environment. Olfactory neurogenesis begins in the subventricular zone where stem cells proliferate and give rise to young undifferentiated neuroblasts that migrate along the rostral migratory stream to the olfactory bulb (OB). Olfaction is crucial for the expression of sexual behavior in rodents. In female rats, the ability to control the rate of sexual interactions (pacing) has important physiological and behavioral consequences. In the present experiment we evaluated if pacing behavior modifies the rate of new cells that reach the main and accessory olfactory bulb. The BrdU marker was injected before and after different behavioral tests which included: females placed in a mating cage (control), females allowed to pace the sexual interaction, females that mated but were not able to control the rate of the sexual interaction and females exposed to a sexually active male. Subjects were sacrificed fifteen days after the behavioral test. We observed a significant increase in the density of BrdU positive cells in the internal cellular layer of the accessory olfactory bulb when females paced the sexual interaction in comparison to the other 3 groups. No differences in the cell density in the main olfactory bulb were found. These results suggest that pacing behavior promotes an increase in density of the new cells in the accessory olfactory bulb.
It is accepted that the main- and accessory- olfactory systems exhibit overlapping responses to pheromones and odorants. We performed whole-cell patch-clamp recordings in adult rat olfactory bulb slices to define a possible interaction between the first central relay of these systems: the accessory olfactory bulb (AOB) and the main olfactory bulb (MOB). This was tested by applying electrical field stimulation in the dorsal part of the MOB while recording large principal cells (LPCs) of the anterior AOB (aAOB). Additional recordings of LPCs were performed at either side of the plane of intersection between the aAOB and posterior-AOB (pAOB) halves, or linea alba, while applying field stimulation to the opposite half. A total of 92 recorded neurons were filled during whole-cell recordings with biocytin and studied at the light microscope. Neurons located in the aAOB (n = 6, 8%) send axon collaterals to the MOB since they were antidromically activated in the presence of glutamate receptor antagonists (APV and CNQX). Recorded LPCs evoked orthodromic excitatory post-synaptic responses (n = 6, aAOB; n = 1, pAOB) or antidromic action potentials (n = 8, aAOB; n = 7, pAOB) when applying field stimulation to the opposite half of the recording site (e.g., recording in aAOB; stimulating in pAOB, and vice-versa). Observation of the filled neurons revealed that indeed, LPCs send axon branches that cross the linea alba to resolve in the internal cellular layer. Additionally, LPCs of the aAOB send axon collaterals to dorsal-MOB territory. Notably, while performing AOB recordings we found a sub-population of neurons (24% of the total) that exhibited voltage-dependent bursts of action potentials. Our findings support the existence of: 1. a direct projection from aAOB LPCs to dorsal-MOB, 2. physiologically active synapses linking aAOB and pAOB, and 3. pacemaker-like neurons in both AOB halves. This work was presented in the form of an Abstract on SfN 2014 (719.14/EE17).
Objective. During the onset of a novel epidemic, there are public health priorities that need to be estimated, such as risk factors for infection, hospitalization, and clinical severity to allocate resources and issue health policies. In this work we calculate the risk of infection and hospitalization by Covid-19 conferred by demographic, lifestyle, and co-morbidity factors. Material and methods. This is a case-control study including the tested individuals for SARS-Cov-2 by RT-PCR officially reported by the Health Secretary of Mexico from January 01 to May 8, 2020 (102,875 subjects). Demographic (sex, age, foreign and immigrant status, native speaking, place of residence), life-style (smoking), and co-morbidities [diabetes, obesity, high blood pressure (HBP), asthma, immunosuppression, chronic obstructive pulmonary disease (COPD), cardiovascular disease other than HBP, chronic kidney disease (CKD), and other not specified diseases (other diseases)] variables were included in this study. The risk of infection and hospitalization conferred by each variable was calculated with univariate (ULR) and multivariate (MLR) logistic regression models. Results. The place of residence (OR=4.91 living in Tijuana City), followed by advanced age (OR=6.71 in 61-70 years-old), suffering from diabetes (OR=1.87) or obesity (OR=1.61), being male (OR=1.55), having HBP (OR=1.52), and notoriously being indigenous (OR=1.49) conferred a higher risk of becoming infected by SARS-CoV-2 in Mexico. Unexpectedly, we found that having asthma (OR=0.63), immunosuppression (OR=0.65) or smoking (OR=0.85) are protective factors against infection, while suffering from COPD does not increase the risk for SARS-CoV-2 infection. In contrast, advanced age (OR=11.6 in ≥ 70 years-old) is the main factor for hospitalization due to Covid-19, followed by some co-morbidities, mainly diabetes (OR=3.69) and HBP (OR=2.79), being indigenous (OR=1.89), male sex (OR=1.67) and the place of residence (OR=4.22 for living in Juarez City). Unlike the protective risk against infection, immunosuppression (OR=2.69) and COPD (OR=3.63), contribute to the risk of being hospitalized, while having asthma (OR=0.7) also provides protection against hospitalization. Conclusions. In addition to confirming that older age, diabetes, HBP and obesity are the main risk of infection and hospitalization by Covid-19, we found that being indigenous, immunosuppression, smoking and asthma protect against infection, and the latter also against hospitalization.
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