Ultrastructural features of NPY-containing neurons in the rat striatum

In the present study, we examined the ultrastructure of striatal neurons containing neuropeptide Y (NPY) which were labeled by an immunohistochemical method using peroxidase-conjugated F(ab) fragments in the rat. Each of the 26 neurons identified had a deeply indented oval nucleus. The cytoplasm, which was mainly concentrated at the emergence of the dendrites, contained an abundant Golgi apparatus and a well-developed granular endoplasmic reticulum. Dendrites were poorly branched and rarely exhibited varicosities or dendritic spines. NPY-immunoreactive (Ir) axons were small in diameter and unmyelinated. These features corresponded to a subpopulation of striatal neurons classified as aspiny type IV in previous Golgi studies. Axon terminals forming symmetrical synapses were numerous on the NPY-Ir perikarya and proximal dendrites. On distal NPY-Ir dendrites, synaptic contacts were mainly of the asymmetrical type, suggesting that NPY neurons are contacted by at least 2 categories of afferent fibers. Several NPY-Ir axonal processes and boutons were found to form symmetrical synapses with dendrites, dendritic spines and perikarya belonging to spiny type neurons. These data were consistent with the view that NPY may act as a neurotransmitter of striatal interneurons. Moreover, the frequent observation of NPY axonal processes in the close vicinity of striatal vessels suggested that NPY might also play a role in the control of cerebral vasomotricity. Thirty hours after intranigral injection of 6-hydroxydopamine to induce a degeneration of nigrostriatal dopamine terminals, some characteristic degenerative boutons were observed in close apposition to NPY-Ir cell bodies, suggesting that NPY neurons are under a direct nigrostriatal dopaminergic influence.     

La nutrition en conditions extrêmes

Nutritional reference intakes are build to cover the nutritional needs of the majority of the “normal“ population in a “normal“ environment. Much work is needed to define references for extreme situations. Beside extreme situations such as pathology, under or over nutrition, the study of other extreme conditions could lead to useful insights in pathophysiological mechanisms. Man adaptation to cold temperatures, altitude or spatial flights leads to the development of experimental models, the utility of which goes far beyond the studied conditions: the regulation of appetite and of the metabolisms of proteins, carbohydrates or calcium provides interesting examples.     

MECP2 duplication syndrome in a patient from Cameroon

MECP2 duplication syndrome (MDS; OMIM 300260) is an X‐linked neurodevelopmental disorder caused by nonrecurrent duplications of the Xq28 region involving the gene methyl‐CpG‐binding protein 2 (MECP2; OMIM 300005). The core phenotype of affected individuals includes infantile hypotonia, severe intellectual disability, very poor‐to‐absent speech, progressive spasticity, seizures, and recurrent infections. The condition is 100% penetrant in males, with observed variability in phenotypic expression within and between families. Features of MDS in individuals of African descent are not well known. Here, we describe a male patient from Cameroon, with MDS caused by an inherited 610 kb microduplication of Xq28 encompassing the genes MECP2, IRAK1, L1CAM, and SLC6A8. This report supplements the public data on MDS and contributes by highlighting the phenotype of this condition in affected individuals of African descent.     

Pharmacological characterization of dopaminergic influence on expression of neuropeptide Y immunoreactivity by rat striatal neurons

Selective unilateral lesion of the nigrostriatal dopamine pathway by the cytotoxin 6-hydroxydopamine was previously shown to enhance the number and staining intensity of neurons expressing neuropeptide Y immunoreactivity in the ipsilateral striatum. This effect was completely reversed by treatment of the 6-hydroxydopamine-injected animals with the directly acting dopamine agonist apomorphine. This finding reinforces our previous hypothesis that changes in striatal neuropeptide Y staining subsequent to 6-hydroxydopamine lesions of this kind reflect changes in intraneuronal neuropeptide Y levels which are directly attributable to the suppression of a tonic dopaminergic control. In contrast to the effect of 6-hydroxydopamine lesion, non-destructive impairment of striatal dopamine transmission by treatments with either the dual dopamine D1/D2 receptor antagonist haloperidol or the dopamine synthesis inhibitor alpha-methylparatyrosine induced a decrease in both the number of neuropeptide Y striatal cells (-29.8% and -34.8%, respectively) and in their labeling intensity. The selective D2-antagonist sulpiride also showed a tendency to reduce the number of neuropeptide Y immunoreactive cells, whereas the selective D1 antagonist SCH 23390 induced a small but constant increase in this number. Taken as a whole, these results suggest that the dopaminergic D1 and D2 receptor subtypes play opposite roles in the dopaminergic control of the striatal neuropeptide Y neuronal system, which may account for the different changes in striatal neuropeptide Y immunostaining observed after 6-hydroxydopamine injury and after non-destructive impairment of nigrostriatal dopaminergic transmission.     

Projections from Areas 18 and 19 to Cat Striate Cortex: Divergence and Laminar Specificity

The results of electrical stimulation experiments [Bullier et al., (1988) Exp. Brain Res., 70, 90 - 98] demonstrated that afferents from areas 18 and 19 contact different functional types of neurons in area 17. We were therefore interested in examining whether these results could be explained by differences in the morphology of the terminals of these two groups of afferent connections to area 17. We also wanted to confirm, by a direct method, our earlier results [Salin et al. (1989) J. Comp. Neurol., 283, 486 - 512] that cortical afferents to area 17 in the cat present extensive divergences. We therefore placed small injections of anterograde tracers in areas 18 and 19 and examined the laminar distributions of terminals thus revealed and the extent of the surface of area 17 contacted by these terminals. Three tracers were used: wheat germ agglutinin - horseradish peroxidase (WGA - HRP), Phaseolus vulgaris leucoagglutinin (Pha-L) and biocytin. The results show that the divergence of these afferent connections are very extensive: 7 - 8 mm in the rotrocaudal direction and 3.5 - 6 mm in the mediolateral direction. In other words, neurons located in a region a few hundreds micron wide in areas 18 or 19 contact a region of area 17 covering several millimeters. Corticocortical connections are therefore not organized in a point-to-point fashion but are strongly divergent. The laminar distributions of terminals from areas 18 and 19 displayed a specific pattern. Area 19 projects most heavily to layers 5 and 6, also terminates in layers 1 - 3 and very little is present in layer 4. In contrast, the afferent terminals from area 18 are heaviest in layers 1, 2, 3, 4A and 5 and are rare in layer 6. Injections placed at different depths in area 18 revealed that upper layer neurons in that area mostly project to layers 1, 2, 3 and 5 in area 17, whereas lower layer neurons send their heaviest projections to layers 4A, 5 and 6 and hardly project to layers 1, 2 and 3.     

Dysfunctional regulation of alphaCaMKII and syntaxin 1B transcription after induction of LTP in the aged rat

Syntaxin 1B and alphaCaMKII are two genes that are upregulated after the induction of LTP and appear to underlie different mechanisms of synaptic plasticity. alphaCaMKII is directly implicated in strengthening the synapses that have been modified, whereas syntaxin 1B has been implicated in a mechanism for the propagation of synaptic plasticity within neural circuits. In these experiments we have investigated whether the regulation of these genes is altered after the induction of LTP in aged rats. We found, three hours after the induction of LTP in the dentate gyrus, that aged rats could be subgrouped into those in which LTP was maintained and those in which LTP had decayed back to basal levels. Both genes were upregulated in young adult rats, whereas there was a differential pattern of LTP-induced expression in the aged rats. Dendritic alphaCaMKII was upregulated in aged rats only when LTP was maintained. In contrast, regulation of syntaxin 1B and alphaCaMKII was absent in the granule cell bodies of the aged rats regardless of whether LTP was maintained or not. These results suggest that molecular mechanisms implicated in two aspects of hippocampal synaptic plasticity malfunction during normal ageing and therefore may have some contributory role in the decline in memory function routinely observed in ageing.     

Dissipation Kinetics of Chlorantraniliprole in Soils of Sugarcane Ecosystem

Dissipation kinetics of chlorantraniliprole was studied in sandy loam soils of sugarcane ecosystem by adopting a rapid analytical method. The recovery of chlorantraniliprole was 91.67 % when extracted with ethyl acetate as against only 65.58 % in acetonitrile-based extraction. An additional cleanup step with primary secondary amine did not enhance the recovery significantly over the no-cleanup method. The ethyl acetate-based extraction followed by direct quantification in HPLC (High-performance liquid chromatography) without any cleanup facilitated rapid quantification of chlorantraniliprole residues. The LOQ (limit of quantification) of the method was 0.01 μg/g. The half-life of chlorantraniliprole was 6.50 and 6.81 days for the recommended and double the recommended doses, respectively.     

Sickle cell disease,sickle trait and the risk for venous thromboembolism: a systematic review and meta-analysis

Background

Globally, sickle cell disease (SCD) is one of the most common haemoglobinopathy. Considered a public health problem, it leads to vessel occlusion, blood stasis and chronic activation of the coagulation system responsible for vaso-occlussive crises and venous thromboembolism (VTE) which may be fatal. Although contemporary observational studies suggest a relationship between SCD or sickle trait (SCT) and VTE, there is lack of a summary or meta-analysis data on this possible correlation. Hence, we propose to summarize the available evidence on the association between SCD, SCT and VTE including deep vein thrombosis (DVT) and pulmonary embolism (PE).

Methods

We searched PubMed and Scopus to identify all cross-sectional, cohort and case-control studies reporting on the association between SCD or SCT and VTE, DVT or PE in adults or children from inception to April 25, 2017. For measuring association between SCD or SCT and VTE, DVT, or PE, a meta-analysis using the random-effects method was performed to pool weighted odds ratios (OR) of risk estimates.

Results

From 313 records initially identified from bibliographic databases, 10 studies were eligible and therefore included the meta-analysis. SCD patients had significantly higher risk for VTE (pooled OR 4.4, 95%CI 2.6–7.5, p?<?0.001), DVT (OR 1.1, 95% CI 1.1–1.2, p?<?0.001) and PE (pooled OR 3.7, 95% CI 3.6–3.8, p?<?0.001) as compared to non SCD-adults. A higher risk of VTE (OR 33.2, 95% CI 9.7–113.4, p?<?0.001) and DVT (OR 30.7, 95% CI 1.6–578.2, p =?0.02) was found in pregnant or postpartum women with SCD as compared to their counterparts without SCD. Compared to adults with SCT, the risk of VTE was higher in adults with SCD (pooled OR 3.1, 95% CI 1.8–5.3, p?<?0.001), and specifically in SCD pregnant or postpartum women (OR 20.3, 95% CI 4.1–102, p?=?0.0003). The risk of PE was also higher in adults with SCD (OR 3.1, 95% CCI 1.7–5.9, p?=?0.0004) as compared to those with SCT. The risk of VTE was higher in individuals with SCT compared to controls (pooled OR 1.7, 95% CI 1.3–2.2, p?<?0.0001), but not in pregnant or postpartum women (OR 0.9, 95% CI 0.3–2.9, p?=?0.863). Compared to controls, SCT was associated with a higher risk of PE (pooled OR 2.1, 95% CI 1.2–3.8, p?=?0.012) but not of DVT (pooled OR 1.2, 95% CI 0.9–1.7, p?=?0.157).

Conclusion

Individuals with SCD, especially pregnant or postpartum women, might have a higher risk of VTE compared to the general population. SCT might also increases the risk of VTE. However, currently available data are not sufficient to allow a definite conclusion. Further larger studies are needed to provide a definitive conclusion on the association between SCD, SCT and VTE.

     

Aetiology of childhood hearing loss in Cameroon (sub-Saharan Africa)

BackgroundSevere hearing loss is a global problem affecting particularly developing countries. There is scarcity of recent published data on the epidemiology of childhood deafness in sub-Saharan Africa.ObjectiveTo determine the etiological profile of severe childhood deafness in Cameroon.MethodsProspective cross-sectional study of patients with a severe hearing loss that started before the age of 15 years. Detailed family and medical history was obtained; careful clinical, otological and audiological examinations were performed.ResultsA total of 582 patients with a severe hearing loss were examined. Prelingual deafness accounted for 75.1% (n = 437), with a mean age at medical diagnosis of 3.3 ± 1.2 years. This late presentation may be explained by limited parental awareness of signs raising suspicion of hearing loss, poor access to health care and the absence of neonatal screening for hearing loss in Cameroon. Identified genetic causes accounted for 14.8% (n = 86), putative environmental causes for 52.6% (n = 306) and unknown causes for 32.6% (n = 190). Amongst Genetic causes, the syndromic hearing loss accounted for 13.1% (n = 12) of cases, the rest being non syndromic (n = 74). Consanguineous families accounted for 5.7% (n = 33) of the whole sample, and 15.1% (n = 13) of genetic cases. No union between deaf parents was observed.ConclusionThese data highlight the possible predominance of putative environmental causes of childhood deafness in Cameroon, and emphasize the need for improved policies for prevention of infectious diseases and for neonatal hearing screening. However, further molecular analyses and targeted CT scan investigations are required to more accurately gauge the contribution of genetics etiologies.