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981.
Palin EJ Hakonen AH Korpela M Paetau A Suomalainen A 《Journal of the neurological sciences》2012,315(1-2):160-163
We studied the genetic background of a family with SCA, showing dominant inheritance and anticipation. Muscle histology, POLG1 gene sequence, neuropathology and mitochondrial DNA analyses in a mother and a son showed typical findings for a mitochondrial disorder, and both were shown to be homozygous for a recessive POLG1 mutation, underlying mitochondrial recessive ataxia syndrome, MIRAS. The healthy father was a heterozygous carrier for the same mutation. Recessively inherited MIRAS mutations should be tested in dominantly inherited SCAs cases of unknown cause, as the high carrier frequency of MIRAS may result in two independent introductions of the mutant allele in the family and thereby mimic dominant inheritance. 相似文献
982.
983.
The neuronal ceroid lipofuscinoses constitute the most common group of childhood neurodegenerative disorders. These devastating disorders still remain without effective treatment. The use of animal models has provided significant information about NCL pathogenesis, highlighting early glial activation and neuron loss in specific brain regions of affected animals. Here, we have characterized the timing and regional-specificity of the pathological events of CLN8 disease utilizing the Cln8 deficient mouse model, Cln8(mnd). We have studied the progression of neuron loss, astrocytosis and microglial activation from early to moderately symptomatic (1, 3 and 5 months) and late symptomatic (8 months) mice. In Cln8 deficiency, the somatosensory pathway comprising the thalamic ventral posterior nucleus (VPM/VPL) and the primary somatosensory cortex (S1BF) was found to be the most affected relay system. Scattered microglia that appeared partially activated were already present at 3 months of age, followed by astrocytosis and the loss of thalamic relay neurons at 5 months of age, with all these phenotypes and glial activation becoming more pronounced with disease progression. Reactive changes followed a similar pattern in the corresponding cortical target regions, but only moderate neuron loss was detected. Compared to the somatosensory system, in the visual thalamocortical pathway, neuron loss appeared relatively late in the disease, at 8 months. Neuron loss was preceded by glial activation in the dorsal lateral geniculate nucleus (LGNd) and in the primary visual cortex (V1). Taken together these data highlight the pathological targeting of the somatosensory thalamocortical pathway in Cln8 deficiency, in common with other forms of NCL. However, in contrast to other previously characterized NCL models, the Cln8(mnd) mouse shows relatively mild and late appearing pathology within the thalamocortical visual pathway. 相似文献
984.
In this review, we present a transdiagnostic emotion dysregulation model of mood and anxiety disorders. This model posits that a triggering event, in conjunction with an existing diathesis, leads to negative or positive affect, depending on the person's affective style. Mood and anxiety disorders are the result of emotion dysregulation of negative affect, coupled with deficiencies in positive affect. The theoretical background of the model is discussed and a range of clinical applications of the model is described. 相似文献
985.
Ramirez SH Haskó J Skuba A Fan S Dykstra H McCormick R Reichenbach N Krizbai I Mahadevan A Zhang M Tuma R Son YJ Persidsky Y 《The Journal of neuroscience》2012,32(12):4004-4016
Previous studies have shown that modulation of the receptor-mediated cannabinoid system during neuroinflammation can produce potent neuroprotective and anti-inflammatory effects. However, in this context, little is known about how selective activation of the cannabinoid type-2 receptor (CB2R) affects the activated state of the brain endothelium and blood-brain barrier (BBB) function. Using human brain tissues and primary human brain microvascular endothelial cells (BMVECs), we demonstrate that the CB2R is highly upregulated during inflammatory insult. We then examined whether the CB2R agonists could attenuate inflammatory responses at the BBB using a mouse model of LPS-induced encephalitis and highly selective CB2R agonists. Visualization by intravital microscopy revealed that administration of JWH133 [(6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran] or a novel resorcinol-based compound, O-1966 (1-[4-(1,1-dimethyl-heptyl)-2,6-dimethoxy-phenyl]-3-methyl-cyclohexanol), greatly attenuated leukocyte adhesion in surface pial vessels and in deep ascending cortical postcapillary venules. BBB permeability assessments with small and large fluorescent tracers showed that CB2R agonists were effective at preventing barrier leakiness after LPS administration. To determine whether the effects by CB2R agonists on barrier protection are not only due to the CB2R modulation of immune cell function, we tested the agonists in vitro with barrier-forming primary BMVECs. Remarkably, the addition of CB2R agonist increased transendothelial electrical resistance and increased the amount of tight junction protein present in membrane fractions. Furthermore, CB2R agonists decreased the induction of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 surface expression in BMVECs exposed to various proinflammatory mediators. Together, these results suggest that pharmacological CB2R ligands offer a new strategy for BBB protection during neuroinflammation. 相似文献
986.
Ville Puisto Harri Rissanen Markku Heli?vaara Olli Impivaara Tuomas Jalanko Heikki Kr?ger Paul Knekt Arpo Aromaa Ilkka Helenius 《European spine journal》2011,20(12):2181-2186
Introduction
Vertebral fractures predict mortality, but little is known about their associations with the causes of death. We studied vertebral fractures for prediction of cause-specific mortality. 相似文献987.
988.
989.
Uku Vainik Alain Dagher Anu Realo Lucía Colodro‐Conde Erik Lykke Mortensen Kerry Jang Ando Juko Christian Kandler Thorkild I.A. Srensen Ren Mttus 《Obesity reviews》2019,20(8):1121-1131
Obesity has inconsistent associations with broad personality domains, possibly because the links pertain to only some facets of these domains. Collating published and unpublished studies (N = 14 848), we meta‐analysed the associations between body mass index (BMI) and Five‐Factor Model personality domains as well as 30 Five‐Factor Model personality facets. At the domain level, BMI had a positive association with Neuroticism and a negative association with Conscientiousness domains. At the facet level, we found associations between BMI and 15 facets from all five personality domains, with only some Neuroticism and Conscientiousness facets among them. Certain personality‐BMI associations were moderated by sample properties, such as proportions of women or participants with obesity; these moderation effects were replicated in the individual‐level analysis. Finally, facet‐based personality “risk” scores accounted for 2.3% of variance in BMI in a separate sample of individuals (N = 3569), 409% more than domain‐based scores. Taken together, personality‐BMI associations are facet specific, and delineating them may help to explain obesity‐related behaviours and inform intervention designs. Preprint and data are available at https://psyarxiv.com/z35vn/ . 相似文献
990.
Žigon Polona Podovšovnik Anuška Ambrožič Aleš Tomšič Matija Hočevar Alojzija Gašperšič Nataša Rotar Žiga Praprotnik Sonja Šemrl Snežna Sodin Čučnik Saša 《Clinical rheumatology》2019,38(2):371-378
Clinical Rheumatology - The international classification criteria for definite antiphospholipid syndrome (APS) include three laboratory measurements: lupus anticoagulant (LA), IgG and IgM isotypes... 相似文献