Autonomic Brain Centers and Pathophysiology of COVID-19.

Accumulating data have now shown strong evidence that COVID-19 infection leads to the occurrence of neurological signs with different injury severity. Anosmia and agueusia are now well documented and included in the criteria list for diagnosis, and specialists have stressed that doctors screen COVID-19 patients for these two signs. The eventual brainstem dysregulation, due to the invasion of SARS CoV-2, as a cause of respiratory problems linked to COVID-19, has also been extensively discussed. All these findings lead to an implication of the central nervous system in the pathophysiology of COVID-19. Here we provide additional elements that could explain other described signs like appetite loss, vomiting, and nausea. For this, we investigated the role of brainstem structures located in the medulla oblongata involved in food intake and vomiting control. We also discussed the possible pathways the virus uses to reach the brainstem, i.e., neurotropic and hematogenous (with its two variants) routes.

Gestational and Lactational Exposure to Malathion Affects Antioxidant Status and Neurobehavior in Mice Pups and Offspring.

Environmental factors such as pesticides are considered key determinants of brain damage and brain dysfunction. In the present work, we investigated the effect of an organophosphate pesticide, i.e., malathion, administrated peri- and postnatally on the antioxidant system as well as on acetylcholine esterase (AChE) activity in the brains of mice pups during the three postnatal weeks. Furthermore, we analyzed the behavior of the offspring just after weaning to assess the eventual effect of the pesticide on anxiety traits and social interaction. Concerning the biochemical biomarkers, the continuous treatment with malathion given either at a low dose of 5 mg/kg or at a medium one, 15 mg/kg, causes alterations in the activities of catalase, superoxide dismutase, glutathione S-transferase, and glutathione peroxidase, accompanied by high level of peroxidation of membrane lipids, indicating a disturbance in intracellular redox homeostasis with subsequent increased intracellular oxidative stress. The effect was more pronounced when the high dose was applied. This was also demonstrated for the activity of AChE, downregulated at all postnatal ages investigated (5, 15, and 21), whereas the low dose (5 mg/kg) did not alter this enzymatic activity which is in line with the absence of locomotor activity alteration as assessed by open field (OF). With regard to this last test, results obtained show also that the treated offspring mice develop an anxiogenic state as evidenced by open field as well as an impairment of social interaction. Altogether, these results provide an accurate characterization of the association between neurobehavioral outcomes and brain alterations following malathion administrated in gestational and lactational periods, even given at low dose, classified as safe, and indicate clearly that the developing brain is sensitively vulnerable to this organophosphate pesticide.

An autoradiographic study of neurotensin receptors in the human hypothalamus.

The aim of the present investigation was to determine a detailed mapping of neurotensin (NT) in the human hypothalamus, the brain region involved in neuroendocrine control. For this, we investigated the presence and the distribution of neurotensin binding sites in the human hypothalamus, using an in vitro quantitative autoradiography technique and the selective radioligand monoiodo-Tyr3-neurotensin (2000Ci/mM). This study was performed on nine adult human postmortem hypothalami. We first determined the biochemical kinetics of the binding and found that binding affinity constants were of high affinity and do not differ significantly between all cases investigated. Our analysis of the autoradiographic distribution shows that NT binding sites are widely distributed throughout the rostrocaudal extent of the hypothalamus. However, the distribution of NT binding sites is not homogenous and regional variations exist. In general, the highest densities are mainly present in the anterior hypothalamic level, particularly in the preoptic region and the anterior boarding limit (i.e. the diagonal band of Broca). Important NT binding site densities are also present at the mediobasal hypothalamic level, particularly in the paraventricular, parafornical and dorsomedial nuclei. At the posterior level, relatively moderate densities could be observed in the mammillary complex subdivisions, apart from the supramammillary nucleus and the posterior hypothalamic area. In conclusion, the present study demonstrates the occurrence of high concentrations of NT binding sites in various structures in many regions in the human adult hypothalamus, involved in the control of neuroendocrine and/or neurovegetative functions.

Developmental pattern of VIP binding sites in the human hypothalamus.

We have studied the developmental patterns of vasoactive intestinal polypeptide (VIP) binding sites in the human hypothalamus. VIP recognition sites were widely distributed throughout the rostrocaudal extent of the hypothalamus. VIP binding was generally low in the fetal and neonatal periods and a tendency in increasing densities was observed during postnatal development. The age comparison of binding density indicates variations in several structures. Thus, the densities were higher in older infants in the preoptic area, lamina terminalis, and infundibular (IN) nucleus. These differences suggest the implication of VIP receptors in the development of this brain structure and the maintenance of its various functions.

Distribution of delta sleep-inducing peptide in the newborn and infant human hypothalamus: an immunohistochemical study

The distribution of delta sleep-inducing peptide immunoreactive cell bodies, fibers, and terminal-like structures was investigated in the normal human hypothalamus during the first postnatal year, using immunohistofluorescence and peroxidase anti-peroxidase techniques. Immunolabeled perikarya were relatively few and were mostly scattered through the anterior (preoptic) and mediobasal regions (infundibular nucleus) of the hypothalamus. DSIP-immunoreactive fibers and terminal-like fibers were observed throughout the entire rostrocaudal extent of the hypothalamus. They exhibit high densities in the preoptic region, the organum vasculosum of lamina terminalis, infundibular nucleus and median eminence. Moderate to low densities of DSIP-immunoreactive fibers were observed in the other hypothalamic structures, located in the anterior and mediobasal regions of hypothalamus, such as periventricular, paraventricular, suprachiasmatic, ventromedial, dorsomedial and parafornical nuclei. In the present study, the analysis of the immunohistochemical pattern of DSIP-immunoreactive neuronal elements in the human infant hypothalamus during the first postnatal year provided evidence of the presence of several differences. We have found qualitative age-related changes in the density of DSIP immunoreactivity in several hypothalamic structures such as the anterior region and the median eminence.