Implication des canaux potassium dépendant du calcium et de faible conductance au cours des processus mnésiques chez le rat (approche comportementale, pharmacologique, biochimique et biomoléculaire)

Cette étude a pour objectif d évaluer l implication des canaux SK (SK1, SK2 et SK3) dans les processus d apprentissage et de mémorisation. Dans un premier temps, nous avons comparé les effets de l apamine, une toxine inactivant les canaux SK composés des sous-unités SK2 et SK3 à ceux de la Lei-Dab7, spécifique, à haute affinité uniquement, de la sous-unité SK2, au cours processus mnésiques. Injectées par voie intracérébroventriculaire, l'apamine induit une facilitation mnésique durant la consolidation des informations alors que la Lei-Dab7 n a aucun effet dans un même contexte de mémorisation. Dans un second temps, nous avons évalué la variation de la densité des canaux SK ainsi que leur expression dans le cerveau de rats à différents stades d'apprentissage. L'apprentissage induit une diminution transitoire de la densité des sites de fixation de l'apamine due à une régulation de l expression des ARNm SK2 et SK3 au niveau de l hippocampe. Ainsi l'inactivation des canaux SK par l'apamine renforcerait l'impact de la "downregulation" transitoire des canaux SK sur l'augmentation de l'excitabilité hippocampique observée lors des processus mnésiques.AIX-MARSEILLE1-BU Sci.St Charles (130552104) / SudocSudocFranceF

Differential effects of two blockers of small conductance Ca(2+)-activated K(+) channels, apamin and lei-DAB7, on learning and memory in rats

International audienceSK channels are responsible for long-lasting hyperpolarization following action potential and contribute to the neuronal integration signal. This study evaluates the involvement of SK channels on learning and memory in rats, by comparing the effects of two SK channel blockers, i.e., apamin which recognizes SK2 and SK3 channels, and lei-Dab7 which binds SK2 channels only. lei-Dab7 totally competes and contests apamin binding on whole brain sections (IC(50): 11.4 nM). Using an olfactory associative task, intracerebroventricular blocker injections were tested on reference memory. Once the task was mastered with one odor pair, it was then tested with a new odor pair. Apamin (0.3 ng), injected before or after the acquisition session, improved new odor pair learning in a retention session 24 hours later, whereas lei-Dab7 (3 ng) did not significantly affect the mnesic processes. These results indicated that the blockage of SK channels by apamin facilitates consolidation on new odor associations; lei-Dab7, containing only SK2 subunits, remains without effect suggesting an involvement of SK3 channels in the modulation of the mnesic processes

DIFFERENTIAL EFFECTS OF TWO BLOCKERS OF SMALL CONDUCTANCE Ca 2+ -ACTIVATED K + CHANNELS, APAMIN AND LEI-DAB7, ON LEARNING AND MEMORY IN RATS

International audienceSK channels are responsible for long-lasting hyperpolarization following action potential and contribute to the neuronal integration signal. This study evaluates the involvement of SK channels on learning and memory in rats, by comparing the effects of two SK channel blockers, i.e., apamin which recognizes SK2 and SK3 channels, and lei-Dab7 which binds SK2 channels only. lei-Dab7 totally competes and contests apamin binding on whole brain sections (IC(50): 11.4 nM). Using an olfactory associative task, intracerebroventricular blocker injections were tested on reference memory. Once the task was mastered with one odor pair, it was then tested with a new odor pair. Apamin (0.3 ng), injected before or after the acquisition session, improved new odor pair learning in a retention session 24 hours later, whereas lei-Dab7 (3 ng) did not significantly affect the mnesic processes. These results indicated that the blockage of SK channels by apamin facilitates consolidation on new odor associations; lei-Dab7, containing only SK2 subunits, remains without effect suggesting an involvement of SK3 channels in the modulation of the mnesic processes

Correspondences between the binding characteristics of a non-natural peptide, Lei-Dab7, and the distribution of SK subunits in the rat central nervous system

International audienceSmall-conductance calcium-activated potassium channels (SK1-SK3 channels) are responsible for long-lasting hyperpolarization following action potential and contribute to the neuronal firing and integration signal. Two peptide toxins: apamin and Leiurotoxin 1, block this SK channels with high affinities. We generated a modified Leiurotoxin 1 (Lei-Dab7) that inhibits SK2 channels with a high selectivity. Competitive binding of radio-iodinated apamin to different rat brain structures, in the presence of native apamin and Lei-Dab7, has shown that dissociation constants differ by a factor of 1000 and thus demonstrated that ligand affinity is as important as ligand selectivity for a specific receptor. However, the lack of ligands discriminating between SK channel subunits is impeding the understanding of the role of each heteromeric SK channel type in different tissues. Our study aims to better understand the molecular combinations of SK channels and their association with specific functional implications. On this purpose, a clustering technique allows us to identify five groups of brain structures reflecting singular profiles of affinity and selectivity of Lei-Dab7 in comparison with apamin. The analysis of correspondences between Lei-Dab7 binding and distribution of SK subunits in these groups of brain structures suggests that functional heteromeric SK channels are involved in specific information processes

Deficits cognitifs chez les enfants et adolescents atteints de drepanocytose (Genotype SS) a Brazzaville

Introduction : La drépanocytose impacte négativement le neurodéveloppement de l’enfant. Objectifs : Déterminer la fréquence des déficits cognitifs chez les enfants et adolescents drépanocytaires homozygotes à Brazzaville ; identifier les facteurs associés. Méthodes : Il s’est agi d’une étude transversale analytique. Elle a porté sur les enfants drépanocytaires homozygotes âgés de 6 à 16 ans. Elle a été réalisée au Centre National de Référence de la Drépanocytose de Brazzaville, de mars à septembre 2019. Les domaines neurocognitifs ont été évalués par l’échelle d’intelligence de Wechsler pour enfants, 5e édition. Les variables d’étude ont été sociodémographiques et cliniques. Résultats : Sur 130 enfants drépanocytaires homozygotes reçus en consultation de routine dans le cadre de leur suivi, 83 (63,84%) présentaient des déficits cognitifs. Parmi eux, 43 (51,80 %) étaient des garçons et 40 (48,20%), des filles. L’âge moyen était de 10,93 ± 2,83 ans. Les patients présentaient des déficits de langage, des habilités visuo-spatiales et des fonctions attentionnelles et exécutives. Les accidents vasculaires cérébraux, l’anémie sévère et l’âge avaient un impact sur ces déficits cognitifs. La mémoire de travail n’était pas altérée. L’intelligence générale était conservée. Conclusion : Dans notre milieu, les déficits cognitifs sont fréquents chez les enfants et adolescents drépanocytaires homozygotes. Les facteurs associés à l’altération des fonctions neurocognitives sont similaires à ceux rapportés dans la littérature. De ce fait, il est important d’inclure une évaluation neurocognitive systématique dans le suivi de ces enfants et de les accompagner par des méthodes pédagogiques adaptées ou des programmes de réhabilitation cognitive.   English title: Cognitive deficits in children and adolescents with sickle cell disease (Genotype SS) in Brazzaville Introduction: Sickle cell disease has an negative impact on neurodevelopment in child. Objectives: To determine the frequency of cognitive deficits in children and adolescents with sickle cell disease (genotype SS) in  Brazzaville; to identify the associated factors. Methods: An analytical prospective study was conducted at the National Center of Reference of Sickle Cell Disease in Brazzaville, from March to September 2019. It included 6-16-year-old children with homozygous sickle cell disease (genotype SS). Neurocognitive domains were evaluated by means of the Wechsler Intelligence Scale for Children, Fifth Version. Analyzed parameters were sociodemographic and clinical. Results: Among the 130 children with homozygous sickle cell disease presenting for a routine clinic visit for follow-up, 83 (63.84%) had cognitive deficits. Of these, there are 43 (51.80 %) boys and 40 (48.20%) girls. Mean age was 10.93 ± 2.83 years. Deficits of language, visuo-spatial functions, attention and executive functions were detected in patients. Strokes, severe anemia and age had an impact on these cognitive deficits. Working memory was not impaired. General intelligence was preserved. Conclusion: In our setting, cognitive deficits are very frequent in children and adolescents with homozygous sickle cell disease. The factors associated with neurocognitive impairment in our patients get closer to those reported in literature. It is important to include a systematic neurocognitive assessment in the follow-up of these children and to support them with adapted teaching methods or cognitive rehabilitation programs. &nbsp