Prostaglandin E2 metabolism in rat brain: Role of the blood-brain interfaces

<p>Abstract</p> <p>Background</p> <p>Prostaglandin E₂(PGE₂) is involved in the regulation of synaptic activity and plasticity, and in brain maturation. It is also an important mediator of the central response to inflammatory challenges. The aim of this study was to evaluate the ability of the tissues forming the blood-brain interfaces to act as signal termination sites for PGE₂by metabolic inactivation.</p> <p>Methods</p> <p>The specific activity of 15-hydroxyprostaglandin dehydrogenase was measured in homogenates of microvessels, choroid plexuses and cerebral cortex isolated from postnatal and adult rat brain, and compared to the activity measured in peripheral organs which are established signal termination sites for prostaglandins. PGE₂metabolites produced <it>ex vivo </it>by choroid plexuses were identified and quantified by HPLC coupled to radiochemical detection.</p> <p>Results</p> <p>The data confirmed the absence of metabolic activity in brain parenchyma, and showed that no detectable activity was associated with brain microvessels forming the blood-brain barrier. By contrast, 15-hydroxyprostaglandin dehydrogenase activity was measured in both fourth and lateral ventricle choroid plexuses from 2-day-old rats, albeit at a lower level than in lung or kidney. The activity was barely detectable in adult choroidal tissue. Metabolic profiles indicated that isolated choroid plexus has the ability to metabolize PGE₂, mainly into 13,14-dihydro-15-keto-PGE₂. In short-term incubations, this metabolite distributed in the tissue rather than in the external medium, suggesting its release in the choroidal stroma.</p> <p>Conclusion</p> <p>The rat choroidal tissue has a significant ability to metabolize PGE₂during early postnatal life. This metabolic activity may participate in signal termination of centrally released PGE₂in the brain, or function as an enzymatic barrier acting to maintain PGE₂homeostasis in CSF during the critical early postnatal period of brain development.</p

Progressive Myoclonus Epilepsy Caused by a Homozygous Splicing Variant of SLC7A6OS

Exome sequencing was performed in 2 unrelated families with progressive myoclonus epilepsy. Affected individuals from both families shared a rare, homozygous c.191A > G variant affecting a splice site in SLC7A6OS. Analysis of cDNA from lymphoblastoid cells demonstrated partial splice site abolition and the creation of an abnormal isoform. Quantitative reverse transcriptase polymerase chain reaction and Western blot showed a marked reduction of protein expression. Haplotype analysis identified a similar to 0.85cM shared genomic region on chromosome 16q encompassing the c.191A > G variant, consistent with a distant ancestor common to both families. Our results suggest that biallelic loss-of-function variants in SLC7A6OS are a novel genetic cause of progressive myoclonus epilepsy. ANN NEUROL 2020Peer reviewe

Case report: 7p22.3 deletion and 8q24.3 duplication in a patient with epilepsy and psychomotor delay—Does both possibly act to modulate a candidate gene region for the patient’s phenotype?

Background: Psychomotor delay, epilepsy and dysmorphic features are clinical signs which are described in multiple syndromes due to chromosomal imbalances or mutations involving key genes implicated in the stages of Early Embryonic Development. In this context, we report a 10 years old Tunisian patient with these three signs. Our objective is to determine the cause of developmental, behavioral and facial abnormalities in this patient.Methods: We used banding cytogenetics (karyotype) and Array Comparative Genomic Hybridization (Array CGH) to this purpose.Results: The karyotype was in favor of a derivative of chromosome 7 in the patient and Array CGH analysis revealed a loss of genetic material in 7p22.3-p22.1 (4,56 Mb) with a gain at 8q24.23-q24 (9.20 Mb) resulting from maternal 7/8 reciprocal translocation. An in silico analysis of the unbalanced region was carried out and showed that the 7p22.3-p22.1 deletion contains eight genes. Among them, BRAT1 gene, previously described in several neurodevelopmental diseases, may be a candidate gene which absence could be correlated to the patient’s phenotype. However, the 8q24.23-q24 duplication could be involved in the phenotype of this patient.Conclusion: In this study, we report for the first time a 7p deletion/8q duplication in a patient with psychomoteur delay, epilepsy and facial dysmorphism. Our study showed that Array CGH still useful for delivering a conclusive genetic diagnosis for patients having neurodevelopmental abnormalities in the era of next-generation sequencing

Finger creases lend a hand in Kabuki syndrome.

International audienceKabuki syndrome (KS) is a rare syndrome associating malformations with intellectual deficiency and numerous visceral, orthopedic, endocrinological, immune and autoimmune complications. The early establishment of a diagnostic of KS leads to better care of the patients and therefore prevents complications such as perception deafness, severe complications of auto-immune diseases or obesity. However, the diagnosis of KS remains difficult because based on the appreciation of facial features combined with other highly variable features. We describe a novel sign, namely the attenuation and/or congenital absence of the IPD crease of the third and fourth fingers associated with limitation of flexion of the corresponding joints, which seems to be specific of KS and could help the clinician to diagnose KS

Nouveaux fixateurs en anatomie pathologique: Etude comparative de 3 fixateurs non formolés FineFix, RCL2, Ethacarn

Le formol est depuis plus d’un siècle le fixateur de référence dans les laboratoires d’anatomie pathologique. Ordepuis quelques années le classement de ce fixateur comme carcinogène par l’OMS a conduit à une modification de laréglementation française mettant en avant la nécessité de diminuer le taux d’exposition à ce fixateur. Avec l’essor de labiologie moléculaire dans les années 90, l’étude des acides nucléiques sur les prélèvements fixés par le formol et ses dérivéss’avère difficile, la cryoconservation est alors préférée pour les études moléculaires. Mais après une quinzaine d’annéed’application, le coût et les contraintes de ce système de conservation par le froid se sont révélés trop importants. Montravail s’intègre dans un projet national visant à tester la substitution de la cryoconservation pour les études moléculaires,voir idéalement au remplacement du formol par de nouveaux fixateurs. Pour cela, trois fixateurs non formolés (FNF) (leFinefix, l’Ethacarn et le RCL2) ont été testés d’une part pour les techniques histologiques et d’autre part pour les techniquesde biologie moléculaire.L’analyse morphologique après coloration à l’HPS a permis de diagnostiquer l’ensemble des tumeurs pulmonaires etcérébrales lors de la fixation par un FNF, avec cependant une conservation moins bonne de la résolution chromatinienne etde l’aspect général du cytoplasme lors de la fixation par le FineFix. L’analyse des immunomarquages a montré une intensitéde marquage globalement plus forte dans le cas des fixateurs non formolés en comparaison de la fixation formolée.La conservation des acides nucléiques après fixation non formolée a été évaluée quantitativement et qualitativement.La disponibilité des acides nucléiques, évaluée par les rendements d’extraction, est identique entre les FNF et lacryoconservation. La pureté des ADN extraits semble meilleure lors de la fixation par le RCL2. Les ADN présentent,quelque soit le FNF, un haut poids moléculaire comparable à celui obtenu après cryoconservation. A l’instar des ADN, ladisponibilité des ARN est semblable entre les fixateurs non formolées et la cryoconservation. En revanche, la qualité desARN après fixation par le FineFix est moindre en comparaison des deux autres fixateurs non formolés et de lacryoconservation. La fixation par l’Ethacarn aboutit aussi dans quelques cas à la conservation d’ARN de moindre qualité par rapport à la cryoconservation. L’ensemble des résultats montre que la conservation tissulaire par le FineFix, quoique déjàutilisé dans certains laboratoires d’anatomie pathologique, est moins bonne en comparaison de celle par l’Ethacarn et leRCL2, tout en restant correcte. La distinction entre ces 2 derniers FNF, moins évidente, donne l’avantage au RCL2.Avant le remplacement définitif du formol et de la cryoconservation par un FNF, plusieurs points doivent êtrevérifiés, telle que la stabilité des prélèvements après plusieurs années et la non toxicité des ces nouvelles substances

Prostaglandin Emetabolism in rat brain: Role of the blood-brain interfaces-0

Nd RH buffer supplemented with PGEand its main potential metabolites (b); c and d are radiochemical chromatograms of RH medium incubated for 45 min in the absence (c) and presence (d) of lateral ventricle choroid plexuses from 2-day-old rats. In c and d the y axis represents radioactivity concentration (dpm/ml) in each collected fraction.<p><b>Copyright information:</b></p><p>Taken from "Prostaglandin Emetabolism in rat brain: Role of the blood-brain interfaces"</p><p>http://www.cerebrospinalfluidresearch.com/content/5/1/5</p><p>Cerebrospinal Fluid Research 2008;5():5-5.</p><p>Published online 4 Mar 2008</p><p>PMCID:PMC2292143.</p><p></p

Prostaglandin Emetabolism in rat brain: Role of the blood-brain interfaces-2

D in the choroidal tissue. The data are expressed as percentage of the total amount of molecule (either remaining PGEor produced 13,14-dihydro-15-keto-PGE), at the end of the 5- and 45-minute incubation period. Mean ± SD, n = 3. Abbreviations as in Fig 2.<p><b>Copyright information:</b></p><p>Taken from "Prostaglandin Emetabolism in rat brain: Role of the blood-brain interfaces"</p><p>http://www.cerebrospinalfluidresearch.com/content/5/1/5</p><p>Cerebrospinal Fluid Research 2008;5():5-5.</p><p>Published online 4 Mar 2008</p><p>PMCID:PMC2292143.</p><p></p

Prostaglandin Emetabolism in rat brain: Role of the blood-brain interfaces-1

Ent the amount of radioactivity associated to each molecular species, relative to the initial radioactivity associated to PGE(see method), after either 5 or 45 minutes of incubation. * and **: different from PGEamount in incubation without choroidal tissue, p < 0.05 and 0.01, respectively, paired student's t-test. Abbreviations: KPGE: 15-keto-PGE, DHKPGE: 13,14-dihydro-15-keto-PGE, BCPGE: bicyclo-PGE.<p><b>Copyright information:</b></p><p>Taken from "Prostaglandin Emetabolism in rat brain: Role of the blood-brain interfaces"</p><p>http://www.cerebrospinalfluidresearch.com/content/5/1/5</p><p>Cerebrospinal Fluid Research 2008;5():5-5.</p><p>Published online 4 Mar 2008</p><p>PMCID:PMC2292143.</p><p></p