Neuropeptides in the posterodorsal medial amygdala modulate central cardiovascular reflex responses in awake male rats

The rat posterodorsal medial amygdala (MePD) links emotionally charged sensory stimuli to social behavior, and is part of the supramedullary control of the cardiovascular system. We studied the effects of microinjections of neuroactive peptides markedly found in the MePD, namely oxytocin (OT, 10 ng and 25 pg; n=6/group), somatostatin (SST, 1 and 0.05 mu M; n=8 and 5, respectively), and angiotensin II (Ang II, 50 pmol and 50 fmol; n=7/group), on basal cardiovascular activity and on baroreflex- and chemoreflex-mediated responses in awake adult male rats. Power spectral and symbolic analyses were applied to pulse interval and systolic arterial pressure series to identify centrally mediated sympathetic/parasympathetic components in the heart rate variability (HRV) and arterial pressure variability (APV). No microinjected substance affected basal parameters. On the other hand, compared with the control data (saline, 0.3 mu L; n=7), OT (10 ng) decreased mean AP (MAP(50)) after baroreflex stimulation and increased both the mean AP response after chemoreflex activation and the high-frequency component of the HRV. OT (25 pg) increased overall HRV but did not affect any parameter of the symbolic analysis. SST (1 mu M) decreased MAP(50), and SST (0.05 mu M) enhanced the sympathovagal cardiac index. Both doses of SST increased HRV and its low-frequency component. Ang II (50 pmol) increased HRV and reduced the two unlike variations pattern of the symbolic analysis (P<0.05 in all cases). These results demonstrate neuropeptidergic actions in the MePD for both the increase in the range of the cardiovascular reflex responses and the involvement of the central sympathetic and parasympathetic systems on HRV and APV.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPERGSUniv Fed Ciencias Saude Porto Alegre, Dept Ciencias Basicas Saude Fisiol, Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Programa Posgrad Neurociencias, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilUniv Fed Ciencias Saude Porto Alegre, Dept Fisioterapia, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilCNPq: 501041/2012-5FAPERGS: 1016957Web of Scienc

Suppressed anti-inflammatory heat shock response in high-risk COVID-19 patients : lessons from basic research (inclusive bats), light on conceivable therapies

The major risk factors to fatal outcome in COVID-19 patients, i.e., elderliness and pre-existing metabolic and cardiovascular diseases (CVD), share in common the characteristic of being chronic degenerative diseases of inflammatory nature associated with defective heat shock response (HSR). The molecular components of the HSR, the principal metabolic pathway leading to the physiological resolution of inflammation, is an anti-inflammatory biochemical pathway that involves molecular chaperones of the heat shock protein (HSP) family during homeostasis-threatening stressful situations (e.g., thermal, oxidative and metabolic stresses). The entry of SARS coronaviruses in target cells, on the other hand, aggravates the already-jeopardized HSR of this specific group of patients. In addition, cellular counterattack against virus involves interferon (IFN)-mediated inflammatory responses. Therefore, individuals with impaired HSR cannot resolve virus-induced inflammatory burst physiologically, being susceptible to exacerbated forms of inflammation, which leads to a fatal “cytokine storm”. Interestingly, some species of bats that are natural reservoirs of zoonotic viruses, including SARS-CoV-2, possess an IFN-based antiviral inflammatory response perpetually activated but do not show any sign of disease or cytokine storm. This is possible because bats present a constitutive HSR that is by far (hundreds of times) more intense and rapid than that of human, being associated with a high core temperature. Similarly in humans, fever is a physiological inducer of HSR while antipyretics, which block the initial phase of inflammation, impair the resolution phase of inflammation through the HSR. These findings offer a rationale for the reevaluation of patient care and fever reduction in SARS, including COVID-19

The subcortical-allocortical-neocortical continuum for the emergence and morphological heterogeneity of pyramidal neurons in the human brain

Human cortical and subcortical areas integrate emotion, memory, and cognition when interpreting various environmental stimuli for the elaboration of complex, evolved social behaviors. Pyramidal neurons occur in developed phylogenetic areas advancing along with the allocortex to represent 70–85% of the neocortical gray matter. Here, we illustrate and discuss morphological features of heterogeneous spiny pyramidal neurons emerging from specific amygdaloid nuclei, in CA3 and CA1 hippocampal regions, and in neocortical layers II/III and V of the anterolateral temporal lobe in humans. Three-dimensional images of Golgi-impregnated neurons were obtained using an algorithm for the visualization of the cell body, dendritic length, branching pattern, and pleomorphic dendritic spines, which are specialized plastic postsynaptic units for most excitatory inputs. We demonstrate the emergence and development of human pyramidal neurons in the cortical and basomedial (but not the medial, MeA) nuclei of the amygdala with cells showing a triangular cell body shape, basal branched dendrites, and a short apical shaft with proximal ramifications as “pyramidal-like” neurons. Basomedial neurons also have a long and distally ramified apical dendrite not oriented to the pial surface. These neurons are at the beginning of the allocortex and the limbic lobe. “Pyramidal-like” to “classic” pyramidal neurons with laminar organization advance from the CA3 to the CA1 hippocampal regions. These cells have basal and apical dendrites with specific receptive synaptic domains and several spines. Neocortical pyramidal neurons in layers II/III and V display heterogeneous dendritic branching patterns adapted to the space available and the afferent inputs of each brain area. Dendritic spines vary in their distribution, density, shapes, and sizes (classified as stubby/wide, thin, mushroom-like, ramified, transitional forms, “atypical” or complex forms, such as thorny excrescences in the MeA and CA3 hippocampal region). Spines were found isolated or intermingled, with evident particularities (e.g., an extraordinary density in long, deep CA1 pyramidal neurons), and some showing a spinule. We describe spiny pyramidal neurons considerably improving the connectional and processing complexity of the brain circuits. On the other hand, these cells have some vulnerabilities, as found in neurodegenerative Alzheimer’s disease and in temporal lobe epilepsy

Análise volumétrica do soma neuronal na amígdala medial póstero-ventral de ratos machos e fêmeas em diferentes fases do ciclo estrial

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Efeitos sistêmicos da obstrução nasal e da respiração oral persistente na criança

O presente trabalho revisa parte da fisiologia nasal e os efeitos sistêmicos da respiração oral associada com a obstrução nasal crônica. São abordadas as conseqüências nocivas da respiração oral persistente sobre os sistemas respiratório, cardiovascular, nervoso, endócrino e imunológico, além de sua influência no desenvolvimento orofacial.The present article reviews some aspects of nasal physiology, the systemic effects of mouth breathing and nasal obstruction. Special attention is given to its side effects on respiratory, cardiovascular, endocrine and immunological system, as well its role in facial development

Dendritic branching features of Golgi-impregnated neurons from the ventral medial amygdala subnuclei of adult male and female rats

The anterodorsal (MeAD) and posteroventral (MePV) subnuclei would form the proposed “ventral” division of the rat medial nucleus of the amygdala (MeA). These parts receive chemosensorial inputs, have gonadal hormone receptors and modulate hypothalamic neuroendocrine secretion and defensive/reproductive behaviors. The aims of this study were: (1) to provide further data on the morphology of Golgi-impregnated dendrites from the MeAD and the MePV of adult rats; and (2) to compare the results obtained for dendritic branching and predominant dendritic spatial distribution in both these subnuclei in males and diestrus females. Dendritic arborization levels, number of branches in each level, distribution of dendrites around the cell body and distally from it, and the preferred spatial distribution of dendritic branches were studied using different techniques and compared between sexes. MeAD and MePV multipolar neurons had spiny dendrites with sparse ramifications. The main statistically significant differences were found in the predominant dendritic spatial distribution in the MeAD (rather medially and laterally in males and ventromedially in females, p < 0.02) and in the MePV (rather medially and mediodorsally in males and ventrally in females, p < 0.01). Results suggest that synaptic information might be processed and integrated differently in the dendrites of males and females in these sex steroid-responsive MeA subnuclei. The inclusion of the MeAD and the MePV in one single “ventral” MeA division is further discussed

Dendritic branching features of posterodorsal medial amygdala neurons of adult male and female rats : further data based in the Golgi method

The posterodorsal portion of the medial amygdalar nucleus (MePD) contains receptors for gonadal hormones and modulates the function of a social behavior network in rodents. The aims of this study were: to provide further data about the morphology of Golgi-impregnated dendrites of neurons from the MePD of adult rats; and, to compare the results obtained for dendritic branching and predominant dendritic spatial distribution in the MePD of males and diestrus females. MePD neurons were classified as bitufted or stellate, their spiny dendrites showed variable lengths, divided sparingly and decreased the number of branches with the distance from the soma. Dendritic arborization levels, number of branches in each level, distribution of the dendrites around the cell body and away from it, and the preferred spatial distribution of dendritic branches were studied according to different techniques and compared between sexes. Statistically significant differences were found in the predominant dendritic spatial distribution in the MePD, males with branches more oriented medially and dorsolaterally and females with more dorsally and ventromedially ones (p ≤ 0.05 in all cases). This result adds another clue to understand how information is processed and integrated in the MePD and within functionally dynamic sex steroids-responsive circuits relevant for reproduction in both sexes

Dendritic spines in the posterodorsal medial amygdala after restraint stress and ageing in rats

Several evidences suggest that the posterodorsal medial amygdala (MePD) can be a relevant part of the rat neural circuitry for the regulation of hypothalamic neuroendocrine secretion and for ontogenetically different behavioral displays. The dendritic spine density of Golgi-impregnated neurons from the MePD was evaluated in young rats following acute or chronic restraint stress and in aged animals (24 months old). Compared to the control group, a single 1 h restraint stress session promoted a decreased spine density (p 0.05). Aged rats showed no difference in this dendritic spine parameter when compared to young adults (p > 0.05). These results indicate that short-term stress (1 h) can affect MePD dendritic spines and that neural plasticity is involved with adaptive responses onwards in restrained rats. On the other hand, brain structural modifications related with ageing appear not to influence the number of certain postsynaptic sites in the MePD of rats