Comment on "The neuroinvasive potential of SARS-CoV-2 may play a role in the respiratory failure of COVID-19 patients".

We have read with great care and interest the article by Li et al The authors provide interesting elements with respect to the possible entry of severe acute respiratory syndrome coronavirus 2 at the brain area and plead for an implication of the central nervous system in respiratory problems linked to coronavirus disease. Here we provide additional elements that support those observations, notably the role of brainstem structures located in the medulla oblongata in modulating respiration. We also discussed the possible pathways the virus uses to cross the brain blood barrier and reach the brainstem.

Sex-specific neurobehavioral and biochemical effects of developmental exposure to Malathion in offspring mice.

Malathion is an organophosphate pesticide (OP) commonly used in agriculture, industry, and veterinary medicine. Sex is a crucial factor in responding to neurotoxicants, yet the sex-specific effects of OP exposure, particularly neurological impairments following chronic low-level exposure remains limited. Our study aims to evaluate the neurobehavioral and biochemical effects of developmental exposure to Malathion across sexes. Pregnant mice were exposed to a low oral dose of Malathion from gestation up to the weaning of the pups, which were individually gavaged with a similar dose regimen until postnatal day 70. Our results show that Malathion decreased body weight and food intake, reduced locomotor activity and recognition memory. Motor coordination and special memory were only altered in females, whereas we found a male-specific effect of Malathion on social behavior and marble burying. These alterations were accompanied by increased malondialdehyde (MDA), decreased brain acetylcholinesterase activity (AChE), and disrupted brain redox homeostasis. Our findings about the effects of Malathion exposure across sexes may, in part, contribute to understanding the dimorphic susceptibilities observed in neurological disorders.

Impact of glyphosate-based herbicide exposure through maternal milk on offspring's antioxidant status, neurodevelopment, and behavior.

Glyphosate-based Herbicide (GBH) is a widely used pesticide that functions as a broad-spectrum, non-selective herbicide. Despite advanced research to describe the neurotoxic potential of GBH, the harmful effects on maternal behavior and neurodevelopment of offspring remain unclear. This study was conducted to highlight the effects of GBH on the antioxidant system, anxiety traits, social interaction, and cognitive and sensorimotor functions in pups exposed to 25 or 50 mg/l daily via their mother's milk. Concerning the biochemical biomarkers, GBH administered during the early stages of development negatively affected the status of antioxidant enzymes and lipid peroxidation in the brain structures of the pups. Furthermore, our results showed a significant decrease in acetylcholinesterase (AChE) specific activity within the brains of treated pups. The results of the behavioral tests indicated that the treated offspring developed anxiety, memory, and sociability disorders, as evidenced by the Open Field, Y-maze, object recognition task, and social interaction tests. Through neurodevelopmental testing, we also showed sensorimotor impairment (righting reflex and negative geotaxis) and abnormal maternal behavior. Altogether, our study clearly demonstrates that the developing brain is sensitive to GBH.

The impact of sociodemographic characteristics on diagnosis and access to disease-modifying treatment for patients with multiple sclerosis in Morocco.

OBJECTIVE: This study aims to determine the link between sociodemographic factors, diagnosis, and access to disease-modifying treatment for patients with multiple sclerosis (MS) in Morocco. METHODS: This study concerned a sample of 520 patients representing seven regions of Morocco. We obtained data from the patient record registers, the patient's files, and a questionnaire. RESULTS: The results showed female dominance (69.4%) in patients with MS (69.4%). Besides, patients with this disease are generally young; their mean age is 35.36. The employment rate among the surveyed population was 24.9%. More than 74.6% have no health care coverage, and 70.4% of the patients investigated live without treatment. The results show a significant association between access to treatment and several sociodemographic factors, such as the patient's job, health care coverage, region, and marital status. There is also a link between these sociodemographic factors and access to diagnosis. CONCLUSIONS: Diagnosis and access to treatment are associated with certain sociodemographic factors such as health insurance coverage, the patient's job, regional belonging, and marital status.

Prevalence and determinants of poor glycaemic control: a cross-sectional study among Moroccan type 2 diabetes patients.

BACKGROUND: Diabetes remains poorly controlled in a high proportion of diabetes patients. This study examines the prevalence of poor glycaemic control and associated factors in type 2 diabetes patients in the Beni-Mellal Khenifra region in Morocco. METHODS: A cross-sectional survey was conducted in 2017 among 1456 diabetes patients attending primary health centres. Demographic and clinical data were collected through face-to-face interviews using structured and pre-tested questionnaires. Anthropometric measurements, including body weight, height and waist circumference were taken using standardized techniques and calibrated equipment. Glycaemic control was assessed in terms of the glycated haemoglobin (HbA1c) level and poor glycaemic control was defined as HbA1c ≥7% and a level <7% reflects good glycaemic control. RESULTS: Of the total participants, 66.3% had poor glycaemic control. Bivariate analysis showed that sex (p=0.010), education level (p=0.013), body mass index (p=0.048), duration of diabetes (p<0.0001) and type of therapeutic regimen (p<0.0001) were significantly associated with HbA1c level. However, multiple logistic regression analyses revealed that only a longer duration of diabetes (OR 1.525 [95% confidence interval {CI} 1.183-1.967], p=0.001) and receiving insulin therapy alone (OR 1.589 [95% CI 1.157-2.183], p=0.004) or a combination of oral antidiabetics with insulin (OR 2.554 [95% CI 1.786-3.653], p<0.001) were significantly associated with inadequate glycaemic control. CONCLUSIONS: Despite the particularities of the region, the findings about glycaemic control and its cross-sectionally associated factors are in line with findings from other regions of Morocco. In this subgroup, the longer duration of diabetes and insulin treatment could constitute a cause leading to poor glycaemic control. However, inverse causality cannot be excluded.

Long lasting effect of acute restraint stress on behavior and brain anti-oxidative status.

Exposure to certain acute stressors results in an immediate behavioral and physiological response to these situations during a significant period of days. The goal of the current study is to evaluate the long-lasting effect of single exposure of restraint stress among mice after 0 h, 24 h, 48 h and 72 h. Five groups of mice are under experiment: a control group and four groups exposed to one session of restraint stress. All these groups have been studied for behavioral tests in order to evaluate their memories. This is done through a Y-labyrinth and an object recognition test, and anxiety by using open field device. In the second part of the study, enzymatic assays (concerning catalase, glutathione s transferase, glutathione peroxidase and superoxide dismutase) are used to evaluate oxidative stress. The enzymatic activity of the antioxidant system is assessed in five brain structures, including the cerebellum, olfactory bulb, spinal bulb, hypothalamus, and hippocampus. The obtained results show that acute restraint stress leads to a decrease in memory function and to the development of an anxious state; concomitant to an increase of locomotor activity afterword. It causes disturbance of antioxidant balance in the brain by developing a state of oxidative stress. Indeed, restraint stress causes a change in anti-oxidant stress enzymatic activity in the brain, notably in post-stress period. In conclusion, acute restraint stress is responsible for altering cognitive functions, especially memory, and the development of anxious behavior, which could be a result of the generation of oxidative stress; effects that are persistent over an important period after the cessation of stress.

Effect of Cold Stress on Neurobehavioral and Physiological Parameters in Rats.

Objective: Cold stress is an important current issue and implementing control strategies to limit its sometimes harmful effects is crucial. Cold is a common stressor that can occur in our work and our occupational or leisure time activities every day. There are substantial studies on the effects of chronic stress on memory and behavior, although, the cognitive changes and anxiety disorders that can occur after exposure to chronic intermittent cold stress are not completely characterized. Therefore, the present study was undertaken with an aim to investigate the effects of chronic intermittent cold stress on body weight, food intake and working memory, and to elucidate cold stress related anxiety disorders using cognitive and behavioral test batteries. Methods: We generated a cold stress model by exposing rats to chronic intermittent cold stress for 5 consecutive days and in order to test for the potential presence of sex differences, a comparable number of male and female rats were tested in the current study. Then, we measured the body weights, food intake and the adrenal glands weight. Working memory and recognition memory were assessed using the Y maze and the Novel Object Recognition (NOR) tasks. While, sex differences in the effects of chronic stress on behavior were evaluated by the elevated plus maze (EPM), open field maze (OF), and Marble burying (MB) tests. Results: We found that 2 h exposure to cold (4°C) resulted in an increase in the relative weight of the adrenal glands in male rats. Given the same chronic stress 5 days of cold exposure (2 h per day), increased weight gain in male rats, while females showed decreased food intake and no change in body weight. Both sexes successfully performed the Y maze and object recognition (OR) tasks, indicating intact spatial working memory performance and object recognition abilities in both male and female rats. In addition, we have shown that stress caused an increase in the level of anxiety in male rats. In contrast, the behavior of the female rats was not affected by cold exposure. Conclusion: Overall, the current results provide preliminary evidence that chronic intermittent cold stress model may not be an efficient stressor to female rats. Females exhibit resilience to cold exposure that causes an increase in the level of anxiety in male rats, which demonstrates that they are affected differently by stress and the gender is an important consideration in experimental design.

Mental health among students with neurodevelopment disorders: case of dyslexic children and adolescents.

Several research studies have been devoted to study the links between emotional disorders and learning disabilities. However, very minimal of this research has focused on dyslexic students. Objective: The objectives of this study were as follows: (1) to assess self-esteem, anxiety, and depression in dyslexic Arabic-speaking children and adolescents and (2) to describe psychiatric comorbidities in these subjects by comparing them to their non-dyslexic peers. Methods: In total, 205 students (56 dyslexics and 149 good readers), pursuing their education in ordinary schools in the Beni Mellal-Khenifra region of Morocco responded to Taylor's Self-Assessment Scale of Anxiety, Beck's Depression Questionnaire, and the Coopersmith Self-Esteem Inventory (SEI). Results: Overall, dyslexics were more anxious, more depressed, and had disturbed self-esteem compared to their non-dyslexic peers. The percentage of psychiatric comorbidity was higher in the dyslexic group. Conclusions: The results of this study highlight the need for a multidisciplinary approach that integrates emotional needs assessment into the rehabilitation care of dyslexic children and adolescents.

Muitos estudos têm pesquisado as ligações entre transtornos emocionais e dificuldades de aprendizagem. No entanto, muito pouco desta pesquisa se concentrou em estudantes disléxicos. Objetivo: Os objetivos deste estudo foram: 1) avaliar a autoestima, ansiedade e depressão em crianças e adolescentes disléxicos falantes do árabe; 2) descrever comorbidades psiquiátricas nesses estudantes, comparando-os com seus pares não disléxicos. Métodos: 205 estudantes (56 disléxicos e 149 bons leitores), alunos de escolas comuns da região de Beni Mellal-Khenifra do Marrocos, responderam à escala de autoavaliação de ansiedade de Taylor, ao questionário de depressão de Beck's e ao inventário de autoestima de Coopersmith (IES). Resultados: Em geral, os disléxicos eram mais ansiosos, mais deprimidos e tiveram distúrbios de autoestima em comparação com seus pares não-disléxicos. O percentual de comorbidade psiquiátrica foi maior no grupo disléxico. Conclusões: Os resultados deste trabalho evidenciam a necessidade de uma abordagem multidisciplinar que integre a avaliação das necessidades emocionais aos cuidados de reabilitação de crianças e adolescentes disléxicos.

Prevalence of overweight/obesity and its associated factors among a sample of Moroccan type 2 diabetes patients.

BACKGROUND: Obesity constitutes a major risk factor for the development of diabetes, and has been linked with poor glycaemic control among type 2 diabetic patients. AIMS: This study examines the prevalence of overweight/obesity and associated factors in type 2 diabetic patients in the Beni-Mellal Khenifra region in Morocco. METHODS: A questionnaire-based cross-sectional study was conducted in 2017 among 975 diabetes patients attending primary health centres. Demographic and clinical data were collected through face-to-face interviews. Anthropometric measurements, including body weight, height and waist circumference, were taken using standardized techniques and calibrated equipment. RESULTS: The prevalence of overweight was 40.4%, the general obesity was 28.8% and the abdominal obesity was 73.7%. Using multivariate analysis, we noted that the general obesity was associated with female sex (AOR= 3,004, 95% CI: 1.761-5.104, P<0.001), increased age (AOR=2.192, 95% CI: 1.116-4.307, P<0.023) and good glycaemic control (AOR=1.594, 95% CI: 1.056-2.407, P=0.027), whereas abdominal obesity was associated wih female sex (AOR=2.654, 95% CI: 1.507-4.671, P<0.001) and insulin treatment (AOR=2.927, 95% CI: 1.031-8.757, P=0.048). CONCLUSION: Overweight, general obesity and abdominal obesity were high among participants, especially among women. Taken together, these findings urge the implementation of a roadmap for this diabetic subpopulation to have a new lifestyle.

Subacute silica nanoparticle exposure induced oxidative stress and inflammation in rat hippocampus combined with disruption of cholinergic system and behavioral functions.

Increasing environmental exposure to silica nanoparticles (SiNPs) and limited neurotoxicity studies pose a challenge for safety evaluation and management of these materials. This study aimed to explore the adverse effects and underlying mechanisms of subacute exposure to SiNPs by the intraperitoneal route on hippocampus function in rats. Data showed that SiNPs induced a significant increase in oxidative/nitrosative stress markers including reactive oxygen species (ROS), malondialdehyde (MDA), protein oxidation (PCO) and nitrite (NO) production accompanied by reduced antioxidant enzyme activity (catalase, superoxide dismutase, and glutathione peroxidase) and decreased glutathione (GSH). Phenotypically, SiNPs exhibited spatial learning and memory impairment in the Morris water maze (MWM) test, a decrease of the discrimination index in the novel object recognition test (NORT) and higher anxiety-like behavior. SiNPs affected the cholinergic system as reflected by reduced acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. In addition, SiNPs significantly increased mRNA expression level of genes related to inflammation (TNF-α, IL-1ß, IL-6, and COX-2) and decreased mRNA expression level of genes related to cholinergic system including choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), AChE, muscarinic acetylcholine receptor M1 (m1AChR) and nicotinic acetylcholine receptors (nAChR). Histopathological results further showed an alteration in the hippocampus of treated animals associated with marked vacuolation in different hippocampus areas. These findings provide new insights into the molecular mechanism of SiNPs-induced hippocampal alterations leading to impairment of cognitive and behavioral functions, and implicating oxidative stress and inflammation in the hippocampus, as well as disruption of cholinergic system.

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.

Continuous Exposure to Inorganic Mercury Affects Neurobehavioral and Physiological Parameters in Mice.

Contamination with mercury is a real health issue for humans with physiological consequences. The main objective of the present study was to assess the neurotoxicological effect of inorganic mercury: HgCl2. For this, adult mice were exposed prenatally, postnatally, and during the adult period to a low level of the metal, and their behavior and antioxidant status were analyzed. First, we showed that mercury concentrations in brain tissue of treated animals showed significant bioaccumulation, which resulted in behavioral deficits in adult mice. Thus, the treated mice developed an anxiogenic state, as evidenced by open field and elevated plus maze tests. This anxiety-like behavior was accompanied by a decrease in social behavior. Furthermore, an impairment of memory in these treated mice was detected in the object recognition and Y-maze tests. The enzymatic activity of the antioxidant system was assessed in eight brain structures, including the cerebral cortex, olfactory bulb, hippocampus, hypothalamus, mesencephalon, pons, cerebellum, and medulla oblongata. The results show that chronic exposure to HgCl2 caused alterations in the activity of catalase, thioredoxin reductase, glutathione peroxidase, superoxide dismutase, and glutathione S-transferase, accompanied by peroxidation of membrane lipids, indicating a disturbance in intracellular redox homeostasis with subsequent increased intracellular oxidative stress. These changes in oxidative stress were concomitant with a redistribution of essential heavy metals, i.e., iron, copper, zinc, and magnesium, in the brain as a possible response to homeostatic dysfunction following chronic exposure. The alterations observed in overall oxidative stress could constitute the basis of the anxiety-like state and the neurocognitive disorders observed.

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.

BDNF regulation in the rat dorsal vagal complex during stress-induced anorexia.

The dorsal vagal complex (DVC) is the satiety reflex-integrating center of adult mammals. Immobilization stress (IS) is known to elicit anorexia and to up-regulate BDNF expression in adult rat forebrain; intra-DVC delivery of BDNF was shown to elicit anorexia. Therefore, we addressed here whether IS would increase BDNF signaling in rat DVC by using PCR and western-blot on microdissected tissue extracts. Significant variations of BDNF expression in DVC after IS include exon V mRNA increase at 3 h, decreases of both protein and exon III mRNA at 24 h, and exon I mRNA decrease at 72 h. At the receptor level, IS elicited a highly significant induction of both full-length and truncated-1 TrkB mRNAs at 24 h after IS. In vivo recruitment of BDNF signaling in DVC during stress thus differs from hypothalamus, the relevance of which to anorexia is discussed.

Mental health among students with neurodevelopment disorders: case of dyslexic children and adolescents / Saúde mental em estudantes com distúrbios de neurodesenvolvimento: um caso de crianças e adolescentes disléxicos

ABSTRACT Several research studies have been devoted to study the links between emotional disorders and learning disabilities. However, very minimal of this research has focused on dyslexic students. Objective: The objectives of this study were as follows: (1) to assess self-esteem, anxiety, and depression in dyslexic Arabic-speaking children and adolescents and (2) to describe psychiatric comorbidities in these subjects by comparing them to their non-dyslexic peers. Methods: In total, 205 students (56 dyslexics and 149 good readers), pursuing their education in ordinary schools in the Beni Mellal-Khenifra region of Morocco responded to Taylor's Self-Assessment Scale of Anxiety, Beck's Depression Questionnaire, and the Coopersmith Self-Esteem Inventory (SEI). Results: Overall, dyslexics were more anxious, more depressed, and had disturbed self-esteem compared to their non-dyslexic peers. The percentage of psychiatric comorbidity was higher in the dyslexic group. Conclusions: The results of this study highlight the need for a multidisciplinary approach that integrates emotional needs assessment into the rehabilitation care of dyslexic children and adolescents.

RESUMO Muitos estudos têm pesquisado as ligações entre transtornos emocionais e dificuldades de aprendizagem. No entanto, muito pouco desta pesquisa se concentrou em estudantes disléxicos. Objetivo: Os objetivos deste estudo foram: 1) avaliar a autoestima, ansiedade e depressão em crianças e adolescentes disléxicos falantes do árabe; 2) descrever comorbidades psiquiátricas nesses estudantes, comparando-os com seus pares não disléxicos. Métodos: 205 estudantes (56 disléxicos e 149 bons leitores), alunos de escolas comuns da região de Beni Mellal-Khenifra do Marrocos, responderam à escala de autoavaliação de ansiedade de Taylor, ao questionário de depressão de Beck's e ao inventário de autoestima de Coopersmith (IES). Resultados: Em geral, os disléxicos eram mais ansiosos, mais deprimidos e tiveram distúrbios de autoestima em comparação com seus pares não-disléxicos. O percentual de comorbidade psiquiátrica foi maior no grupo disléxico. Conclusões: Os resultados deste trabalho evidenciam a necessidade de uma abordagem multidisciplinar que integre a avaliação das necessidades emocionais aos cuidados de reabilitação de crianças e adolescentes disléxicos.

A single polycystic kidney disease 2-like 1 channel opening acts as a spike generator in cerebrospinal fluid-contacting neurons of adult mouse brainstem.

Cerebrospinal fluid contacting neurons (CSF-cNs) are found around the central canal of all vertebrates. They present a typical morphology, with a single dendrite that projects into the cavity and ends in the CSF with a protuberance. These anatomical features have led to the suggestion that CSF-cNs might have sensory functions, either by sensing CSF movement or composition, but the physiological mechanisms for any such role are unknown. This hypothesis was recently supported by the demonstration that in several vertebrate species medullo-spinal CSF-cNs selectively express Polycystic Kidney Disease 2-Like 1 proteins (PKD2L1). PKD2L1 are members of the 'transient receptor potential (TRP)' superfamily, form non-selective cationic channels of high conductance, are regulated by various stimuli including protons and are therefore suggested to act as sensory receptors. Using patch-clamp whole-cell recordings of CSF-cNs in brainstem slices obtained from wild type and mutant PKD2L1 mice, we demonstrate that spontaneously active unitary currents in CSF-cNs are due to PKD2L1 channels that are capable, with a single opening, of triggering action potentials. Thus PKD2L1 might contribute to the setting of CSF-cN spiking activity. We also reveal that CSF-cNs have the capacity of discriminating between alkalinization and acidification following activation of specific conductances (PKD2L1 vs. ASIC) generating specific responses. Altogether, this study reinforces the idea that CSF-cNs represent sensory neurons intrinsic to the central nervous system and suggests a role for PKD2L1 channels as spike generators.

Developmental dynamics of neurotensin binding sites in the human hypothalamus during the first postnatal year.

The aim of the present study was to determine a detailed mapping of neurotensin (NT) in the human hypothalamus, during the first postnatal year using an in vitro quantitative autoradiography technique and the selective radioligand monoiodo-Tyr3-NT. Ten human postmortem hypothalami obtained from control neonates and infants (aged from 2 h to 1 year of postnatal age) were used. The biochemical kinetics of the binding in all obtained in this study revealed that the binding affinity constants were of high affinity (in the nanomolar range) and did not differ significantly between all cases investigated. Furthermore, competition experiments show insensitivity to levocabastine and were in favor of the presence of the high affinity site of NT receptor. Autoradiographic distribution showed that NT binding sites were widely distributed throughout the rostrocaudal extent of the hypothalamus. However, the distribution of NT binding sites was not homogenous and regional variations exist. In general, the highest densities were mainly present in the anterior hypothalamic level, particularly in the preoptic area. High NT binding site densities are also present at the mediobasal hypothalamic level, particularly in the paraventricular, parafornical, and dorsomedial nuclei. At the posterior level, low to very low densities could be observed in all the mammillary complex subdivisions, as well as the posterior hypothalamic area. Although this topographical distribution is almost identical during the postnatal period analyzed, age-related variations exist in discrete structures of the hypothalamus. The densities were higher in neonates/less aged infants than older infants in preoptic area (medial and lateral parts). The developmental profile is characterized by a progressive decrease from the neonate period to 1 year of postnatal age with a tendency to reach adult levels. On the other hand, the low levels of NT binding sites observed in posterior hypothalamus did not vary during the first postnatal year. They contrast in that with the very high levels we reported previously in adult. In conclusion, the present study demonstrates the occurrence of high NT binding sites density in various structures in many regions in the human neonate/infant hypothalamus, involved in the control of neuroendocrine and/or neurovegetative functions.

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.

Modulation of orexigenic and anorexigenic peptides gene expression in the rat DVC and hypothalamus by acute immobilization stress.

We studied the long term effects of a single exposure to immobilization stress (IS) (1 h) on the expression of anorexigenic (Pro-opiomelanocortin: POMC and cocaine amphetamine related transcript: CART) and orexigenic (neuropeptide Y:NPY, Agouti related peptide: AgRP) factors in hypothalamus and dorso vagal complex (DVC). We showed, by using RT-PCR that in the hypothalamus, that the mRNAs of POMC and CART were up-regulated at the end of IS and up to 24 h. This up regulation persists until 48-72 h after IS for CART only. In the DVC, their expressions peak significantly at 24 h post stress and decline afterwards; CART mRNA is down regulated after 48 h post stress. NPY and AgRP mRNAs show a gradual increase just after the end of IS. The up regulation is significant only at 24 h after stress for AgRP but remains significantly higher for NPY compared to controls. In DVC, the mRNAs of the two factors show generally a similar post stress pattern. A significant increase jut after the end of IS of rats which persists up to 24 h after is firstly noticed. The levels tend then to reach the basal levels although, they were slightly but significantly higher up to 72 h after stress for mRNA NPY. The comparison between the expression profiles of anorexigenic and the two orexigenic peptides investigated shows the presence of a parallelism between that of POMC and AgRP and that of CART and NPY when each brain region (hypothalamus and DVC) is considered separately. It seems that any surge in the expression of each anorexigenic factor stimulates the expression of those of corresponding and appropriated orexigenic one. These last reactions from orexigenic peptides tend to attenuate the anorexigenic effects of CART and POMC and by consequent to abolish the anorexia state generated by stress.