scholarly journals THU0223 THE NEUROPSYCHIATRIC PHENOTYPE OF NZB/W LUPUS-PRONE MOUSE MODEL AT PRE-NEPHRITIC AND NEPHRITIC STAGES OF THE DISEASE: MURINE MODEL RECAPITULATES HUMAN DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 338.2-339
Author(s):  
D. Nikolopoulos ◽  
A. Polissidis ◽  
K. Karali ◽  
D. Boumpas

Background:The pathogenesis of neuropsychiatric lupus (NPSLE) remains ill-defined due to limited access to tissue and the diversity and complexity of clinical manifestations with most evidence deriving from animal studies in MLR/lpr lupus-prone mouse.Objectives:To phenotype and characterize the neuropsychiatric disease in New Zealand Black/White (NZΒ/W) F1 strain; a spontaneous lupus prone mouse which is characterized by systemic autoimmunity.Methods:Mice were tested in a comprehensive behavioral test battery to assess possible effects on general depressive-like disorders, anxiety, cognitive function and motor performance/coordination. The following tests were conducted in the same order for all subjects (All females, NZB/W strain n=13 and C57BL/6 n=14) at 3 and 6 months of age: Open field, Novel object recognition (NOR), Novel object location (NOL), Elevated plus maze (EPM), Rotarod, Tail suspension test (TST), Prepulse inhibition (PPI), and Sucrose preference test (SPT). For comparisons, statistical significance was indicated as a two-sided P<0.05.Results:NZB/W mice at 3 months and 6 months of age exhibit depressive-like disorder as assessed by SPT and TST (P <0.05 and <0.0001, respectively). Anxiety-like phenotype was evident in lupus-prone mice at both time points based on EPM test (Graph 1). Open-field test revealed decreased locomotor activity and rotarod (Graph 2) showed impaired motor coordination in 3 month-old and 6 month-old NZB/W mice (P<0.001 and <0.01, respectively). NZB/W mice exhibit cognitive dysfunction at 3 and 6 months of age based on NOR test (P<0.05). No differences in cognitive function was observed between the two groups (P=0.11). Prepulse inhibition test revealed decreased sensorimotor gating in 3 month-old NZB/W mice, a difference not reaching statistical significance (P=.078). It was not possible to interpret correctly the PPI at second time point (6 months of age) due to age-related hearing loss in B6 at 6 month-old. NZB/W become more anxious over the course of the disease as assessed by EPM (3 mo. versus 6 mo. P<0.001, paired t-test, Graph 1).Conclusion:The NZB/W lupus-prone strain exhibit depressive-like behavior, anxiety, cognitive impairment and motor disturbances both at early and late stages of the disease. This polygenic murine model may be more suitable for investigating the autoimmunity-mediated neuroinflammation in human SLE.Disclosure of Interests: :None declared

2021 ◽  
Vol 13 ◽  
Author(s):  
Tao Yue ◽  
Yu Chen ◽  
Qi Zheng ◽  
Zihao Xu ◽  
Wei Wang ◽  
...  

Strong links between hearing and cognitive function have been confirmed by a growing number of cross-sectional and longitudinal studies. Seniors with age-related hearing loss (ARHL) have a significantly higher cognitive impairment incidence than those with normal hearing. The correlation mechanism between ARHL and cognitive decline is not fully elucidated to date. However, auditory intervention for patients with ARHL may reduce the risk of cognitive decline, as early cognitive screening may improve related treatment strategies. Currently, clinical audiology examinations rarely include cognitive screening tests, partly due to the lack of objective quantitative indicators with high sensitivity and specificity. Questionnaires are currently widely used as a cognitive screening tool, but the subject’s performance may be negatively affected by hearing loss. Numerous electroencephalogram (EEG) and magnetic resonance imaging (MRI) studies analyzed brain structure and function changes in patients with ARHL. These objective electrophysiological tools can be employed to reveal the association mechanism between auditory and cognitive functions, which may also find biological markers to be more extensively applied in assessing the progression towards cognitive decline and observing the effects of rehabilitation training for patients with ARHL. In this study, we reviewed clinical manifestations, pathological changes, and causes of ARHL and discussed their cognitive function effects. Specifically, we focused on current cognitive screening tools and assessment methods and analyzed their limitations and potential integration.


PLoS Medicine ◽  
2006 ◽  
Vol 3 (8) ◽  
pp. e310 ◽  
Author(s):  
Rajendra S Apte ◽  
Jennifer Richter ◽  
John Herndon ◽  
Thomas A Ferguson

2021 ◽  
pp. 1-5
Author(s):  
Hesam Khodadadi ◽  
Évila Lopes Salles ◽  
Abbas Jarrahi ◽  
Vincenzo Costigliola ◽  
MB Khan ◽  
...  

There is a dire need for due innovative therapeutic modalities to improve outcomes of AD patients. In this study, we tested whether cannabidiol (CBD) improves outcomes in a translational model of familial AD and to investigate if CBD regulates interleukin (IL)-33 and triggering receptor expressed on myeloid cells 2 (TREM2), which are associated with improved cognitive function. CBD was administered to 5xFAD mice, which recapitulate early onset, familial AD. Behavioral tests and immunoassays were used to evaluate cognitive and motor outcomes. Our findings suggest that CBD treatment enhanced IL-33 and TREM2 expression, ameliorated the symptoms of AD, and retarded cognitive decline.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 309
Author(s):  
Pachiappan Arjunan ◽  
Radhika Swaminathan ◽  
Jessie Yuan ◽  
Mohamed Elashiry ◽  
Amany Tawfik ◽  
...  

Emerging evidence underscores an association between age-related macular degeneration (AMD) and periodontal disease (PD), yet the biological basis of this linkage and the specific role of oral dysbiosis caused by PD in AMD pathophysiology remains unclear. Furthermore, a simple reproducible model that emulates characteristics of both AMD and PD has been lacking. Hence, we established a novel AMD+PD murine model to decipher the potential role of oral infection (ligature-enhanced) with the keystone periodontal pathogen Porphyromonas gingivalis, in the progression of neovasculogenesis in a laser-induced choroidal-neovascularization (Li-CNV) mouse retina. By a combination of fundus photography, optical coherence tomography, and fluorescein angiography, we documented inflammatory drusen-like lesions, reduced retinal thickness, and increased vascular leakage in AMD+PD mice retinae. H&E further confirmed a significant reduction of retinal thickness and subretinal drusen-like deposits. Immunofluorescence microscopy revealed significant induction of choroidal/retinal vasculogenesis in AMD+PD mice. qPCR identified increased expression of oxidative-stress, angiogenesis, pro-inflammatory mediators, whereas antioxidants and anti-inflammatory genes in AMD+PD mice retinae were notably decreased. Through qPCR, we detected Pg and its fimbrial 16s-RrNA gene expression in the AMD+PD mice retinae. To sum-up, this is the first in vivo study signifying a role of periodontal infection in augmentation of AMD phenotype, with the aid of a pioneering AMD+PD murine model established in our laboratory.


Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1130
Author(s):  
Michio Hashimoto ◽  
Kentaro Matsuzaki ◽  
Shahdat Hossain ◽  
Tomoko Ito ◽  
Harumi Wakatsuki ◽  
...  

Oxidative stress plays an important role in age-associated cognitive decline. We recently reported that dietary intake of perilla seed oil (PO), a rich source of α-linolenic acid (LNA, C18:3, ω-3), helps in maintaining good mental health in adults. This study aimed to investigate the impacts of dietary PO intake on cognitive functions and mental health in healthy, elderly Japanese individuals. Seventy-five healthy volunteers aged 64–84 years were randomly divided into two groups: a control group and a PO-administered group. At baseline and at 12 months of intervention, cognitive function, mental health condition, fatty acid profile of the red blood cell plasma membranes (RBC-PM), and serum biochemical parameters were evaluated. Results showed that serum biological antioxidant potential and LNA levels in the RBC-PM at 12 months after the trial were significantly higher in the PO group compared to the control group. Further, both the cognitive function measures, as evaluated by the Frontal Assessment Battery test and the apathy scores, tended to be improved after 12 months in the PO group. Our results demonstrate that dietary PO intake enhances the antioxidant potential and prevents the age-related cognitive and mental decline in healthy elderly individuals by enhancing the blood LNA levels.


PEDIATRICS ◽  
1994 ◽  
Vol 93 (4) ◽  
pp. 624-630
Author(s):  
Matthew Gesner ◽  
Vana Papaevangelou ◽  
Song-He Chen ◽  
Tiina Moore ◽  
Keith Krasinski ◽  
...  

Objective. The age-related changes in the proportion of CD4 and CD8 lymphocytes in human immunodeficiency virus (HIV)-seronegative children born to HIV-infected mothers (seroreverters) were compared with the changes in these lymphocyte subsets in children born to seronegative women to assess a possible effect of exposure to HIV without infection. Design. There were 146 seroreverter and 72 seronegative children. The median CD4 and CD8 percentages for each of these two groups of children were compared retrospectively at 3-month intervals from birth through 27 months and at a tenth interval for the time beyond 27 months. The weighted average of the within-subject rate of change of CD4 and CD8 percentages were also compared between the two groups. Finally, for each subject, the proportion of the subject's CD4 percentage assays which were &lt;10th percentile of the entire study population (30%) was calculated, and the distributions of the subject-specific proportions were then compared between the seronegative and seroreverter groups using the Wilcoxon rank sum test. The proportion of CD8 assays &lt;10th percentile (12%) or &gt;90th percentile (26%) were also computed for each subject, and the distributions of the proportions were compared similarily. Results. The median CD4 percentage for seroreverter children was lower than that for the seronegative children at every interval from birth through 27 months and for the last interval for values obtained at greater than 27 months, although the comparison was statistically significant only at the 4- to 6-month period. The weighted average of the within-subject rate of change of CD4 percentage was -0.09 and -3.0 per year (P .04), and of CD8 percentage was 1.3 and 1.0 (P = .67), for the seroreverter and seronegative children, respectively. There were significantly more children in the seroreverter group than in the seronegative group who had repeated assays in which the CD4 percentage was &lt;10th percentile for age (P &lt;.00005). In addition, there was a subset of 10 seroreverter children (6.8%) who had CD4 percentages &lt;30% on &gt;50% of their assays, as compared with only one (1.4%) seronegative child. The proportion of CD8 assays &lt;10th percentile or &gt;90th percentile were not significantly different between the two groups of children. Conclusions. The CD4 proportions were persistently lower in the seroreverter than in the seronegative population, although only reaching statistical significance in 1 of 10 3-month intervals. This finding may be due to a subgroup of seroreverter children who have persistently low CD4 lymphocyte percentages.


Author(s):  
Luciano Mesquite Simmo ◽  
Carissa Fouad Ibrahim ◽  
Senice Alvarenga Rodrigues Silva ◽  
Thai Nunes Andrade ◽  
Doora Faleiros Leite ◽  
...  

Objective: To compare the vision-targeted health related quality of life (HRQOL) between neuro-ophthalmological patients and other eye diseases by the National Eye Institute 25-Item Visual Function Questionnaire. Methods: Cross sectional study with a control group and patients with the following pathologies: primary open-angle glaucoma (POAG), diabetic retinopathy (DR), age-related macular degeneration (ARMD), non-arteritic ischemic optic neuropathy (NAION), intracranial hypertension (IH), optic neuritis (ON), ptosis and cataract. Results: All comparisons of the subscales scores among the control group and the patient groups were statistically significant (p<0.05) except for “ocular pain” (p=0.160), “social functioning” (p=0.052) and “peripheral vision” (p=0.112). The control group had the best scores across all dimensions of the NEI VFQ-25. Interestingly, the ARMD and cataract groups presented the best and worst total scores of NEI VFQ-25, respectively. The lowest subscales scores were found in the cataract, in the NAION/ON, and in the POAG groups. Finally, the comparison between the NAION/ON/IH patients and the other eye diseases did not show statistical significance in any subscale. Conclusion: The NEI VFQ-25 showed the impact of various eye conditions in vision-targeted HRQOL, and no difference was measured between neuro-ophthalmological patients and other eye diseases


2015 ◽  
Vol 67 (6) ◽  
pp. 1510-1518
Author(s):  
S.A. Headley ◽  
T.R. Santos ◽  
L. Bodnar ◽  
J.P.E. Saut ◽  
A.P. Silva ◽  
...  

This study investigated the occurrence of canine distemper virus (CDV) by evaluating the presence of viral RNA within urine samples of dogs from Uberlândia, MG, with clinical manifestations suggestive of infection by CDV by targeting the CDV N gene. Of the clinical samples collected ( n =33), CDV viruria was detected in 45.5%. Five dogs died spontaneously; all had characteristic CDV-associated histopathological alterations and demonstrated CDV viruria. Statistical analyses revealed that the age, gender, breed, or the organ system of the dog affected had no influence on the occurrence of canine distemper. Myoclonus and motor incoordination were the most significant neurological manifestations observed. A direct association was observed between keratoconjunctivitis and dogs with CDV viruria. These findings suggest that CDV viruria in symptomatic dogs might not be age related, and that symptomatic dogs can demonstrate clinical manifestations attributed to CDV without viruria identified by RT-PCR. Additionally, the results of the sequence identities analysed have suggested that all Brazilian wild-type strains of CDV currently identified are closely related and probably originated from the same lineage of CDV. Nevertheless, phylogenetic analyses suggest that there are different clusters of wild-type strains of CDV circulating within urban canine populations in Brazil.


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