Search

Item does not contain fulltext Research into the development of Alzheimer's disease (AD) provides increasing evidence that vascular risk factors, including high serum cholesterol, might influence the progression of cognitive impairment and neural degeneration. In this study, we investigated the effects of high dietary cholesterol intake and the cholesterol-lowering liver X receptor-agonist T0901317 on capillary density, amyloid-beta deposition, and presynaptic boutons in the hippocampus of adult (8 months) and aged (15 months) AbetaPPswe-PS1dE9 and wild-type mice to elucidate how cholesterol may affect neurodegenerative processes in aging and AD. Our results show increased number of presynaptic boutons in 15-month-old AbetaPP-PS1 mice compared to age-matched wild-type animals, but no difference at 8 months of age. High cholesterol intake accelerated this response by increasing the amount of presynaptic boutons at 8 and 15 months of age, while T0901317 intake decreased the amount of presynaptic boutons in 15-month-old AbetaPP-PS1 mice. These findings suggest a synaptic compensatory response to maintain connectivity during aging. We hypothesize that high cholesterol intake may cause impaired cerebral blood flow inducing ischemia, fortifying the above mentioned hypothesis of a compensatory mechanism. Contrarily, cholesterol-lowering agents may positively influence cerebral circulation, thereby diminishing aggravation of AD-like pathology.

In the diagnostics of social phobia in adults the SASKO self-report questionnaire serves as an instrument that measures social anxiety and social deficits as two separate dimensions. This paper describes the development of an adaptation of the SASKO for adolescents (SASKO-J) and verifies its applicability, factor structure, and psychometric properties. The factor structure and reliability of the SASKO-J were evaluated in an unselected sample of 228 German students from grades 7 to 11 (M = 14.77 years, SD = 1.33; 50% girls). In a second sample of 115 students the validity was examined (M = 15.84, SD = 1.65; 61% girls). Confirmatory factor analysis confirmed the five-factor structure of the SASKO (two anxiety and two deficit related factors and an additional factor “loneliness”). With the exception of the subscale “information-processing deficits”, the internal consistencies were satisfactory to good (0.77≤ α ≤0.88). The results regarding convergent and divergent validity were also good. Students from different types of school differed in their levels of social anxiety, girls reported significantly more fear of rejection than boys, and the youngest students had the highest level of symptoms. Future research should address the optimizing of the subscale “information-processing deficits” and should examine the psychometric properties of the SASKO-J in a clinical sample. Open-Access-Publikatonsfonds 2015 peerReviewed

International audience; Autism spectrum disorders comprise a range of neurodevelopmental disorders characterized by deficits in social interaction and communication, and by repetitive behaviour. Mutations in synaptic proteins such as neuroligins, neurexins, GKAPs/SAPAPs and ProSAPs/Shanks were identified in patients with autism spectrum disorder, but the causative mechanisms remain largely unknown. ProSAPs/Shanks build large homo- and heteromeric protein complexes at excitatory synapses and organize the complex protein machinery of the postsynaptic density in a laminar fashion. Here we demonstrate that genetic deletion of ProSAP1/Shank2 results in an early, brain-region-specific upregulation of ionotropic glutamate receptors at the synapse and increased levels of ProSAP2/Shank3. Moreover, ProSAP1/Shank2(-/-) mutants exhibit fewer dendritic spines and show reduced basal synaptic transmission, a reduced frequency of miniature excitatory postsynaptic currents and enhanced N-methyl-d-aspartate receptor-mediated excitatory currents at the physiological level. Mutants are extremely hyperactive and display profound autistic-like behavioural alterations including repetitive grooming as well as abnormalities in vocal and social behaviours. By comparing the data on ProSAP1/Shank2(-/-) mutants with ProSAP2/Shank3αβ(-/-) mice, we show that different abnormalities in synaptic glutamate receptor expression can cause alterations in social interactions and communication. Accordingly, we propose that appropriate therapies for autism spectrum disorders are to be carefully matched to the underlying synaptopathic phenotype.