Cannabidiol Ameliorates Cognitive Function via Regulation of IL-33 and TREM2 Upregulation in a Murine Model of Alzheimer’s Disease

2021 ◽  
pp. 1-5
Author(s):  
Hesam Khodadadi ◽  
Évila Lopes Salles ◽  
Abbas Jarrahi ◽  
Vincenzo Costigliola ◽  
MB Khan ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cognitive Decline ◽  
Murine Model ◽  
Early Onset ◽  
Behavioral Tests ◽  
Translational Model ◽  
Therapeutic Modalities ◽  
Model Of Alzheimer’S Disease ◽  
5Xfad Mice ◽  
Motor Outcomes

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.

scholarly journals Intermittent Fasting Alleviates Diabetes-induced Cognitive Decline via Gut Microbiota-metabolites-brain Axis (OR32-04-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Zhigang Liu ◽  
Tian Yuan ◽  
Xiaoshuang Dai ◽  
Lin Shi ◽  
Xuebo Liu
Keyword(s):  
Cognitive Function ◽  
Gut Microbiota ◽  
Cognitive Decline ◽  
Critical Role ◽  
Development Program ◽  
Plasma Metabolites ◽  
Intermittent Fasting ◽  
Metabolic Function ◽  
Behavioral Tests ◽  
Omics Analysis

Abstract Objectives Cognitive decline is one of severe type 2 diabetes complications. Intermittent fasting (IF) is a promising dietary intervention for T2D risk reduction, but its protective effect and mechanism on diabetic cognitive dysfunction remain elusive. Gut microbiota plays a vital role interphasing diet and host physiology and pathology and highly affected by the dietary composition and patterns. It has been reported that the microbiota homeostasis is essential for maintenance of gut health and for modulating cognitive function. We hypothesized that gut microbiota might play a pivotal role in mediating protective effects of IF on diabetes-induced cognitive decline. Methods After a 28-day IF regimen treatment, cognitive behavioral tests and brain insulin signaling were assessed on db/db mice. The microbiota-metabolites-brain axis alterations were detected by multiple-omics analysis (transciptomics, 16S rRNA sequencing and metabolomics). A intergrade multi-omics analysis was performed to analyze the correlation among gut microbiota, plasma metabolites, and hippocampal gene expression. Results Here we found that a 28-day Intermittent fasting (IF) regimen improved cognitive deficits in db/db mice via a microbiota-metabolites-brain axis assessed by behavioral tests and multiple-omics analysis: IF activated AMPK/PGC1α signaling, enhanced mitochondrial biogenesis in hippocampus and elevated genes enriched in hippocampal metabolic function. Moreover, IF re-structured gut microbiota and improved plasma microbial metabolites in relation to diabetes and cognitive function, e.g., serotonin, 3-Indolepropionic acid, and bile acids. Integration of multi-omics data demonstrated strong links between IF-related genes, gut microbiome and metabolites. Furthermore, removal of gut microbiota with antibiotics partly abolished the observed benefits of IF on cognition and hippocampal metabolic function. Conclusions Taken together, the present study suggests a critical role of gut microbiota in connecting peripheral metabolism with brain function, which could lead to novel interventions against metabolism-implicated neurodegenerative pathophysiologies. Funding Sources This work was financially supported by the National Key Research and Development Program of China, National Natural Science Foundation of China.

Altered brain development in an early-onset murine model of Alzheimer's disease

2015 ◽  
Vol 36 (2) ◽  
pp. 638-647 ◽  
Author(s):  
R. Allemang-Grand ◽  
J. Scholz ◽  
J. Ellegood ◽  
L.S. Cahill ◽  
C. Laliberté ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Development ◽  
Murine Model ◽  
Early Onset ◽  
Model Of Alzheimer’S Disease

Early intrathecal infusion of everolimus restores cognitive function and mood in a murine model of Alzheimer's disease

2019 ◽  
Vol 311 ◽  
pp. 88-105 ◽  
Author(s):  
Tommaso Cassano ◽  
Alessandro Magini ◽  
Stefano Giovagnoli ◽  
Alice Polchi ◽  
Silvio Calcagnini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Murine Model ◽  
Model Of Alzheimer’S Disease ◽  
Intrathecal Infusion

scholarly journals Early-but Not Late-Onset Hypertension Is Related to Midlife Cognitive Function

Hypertension ◽  
2021 ◽  
Vol 77 (3) ◽  
pp. 972-979
Author(s):  
Karri Suvila ◽  
Joao A.C. Lima ◽  
Yuichiro Yano ◽  
Zaldy S. Tan ◽  
Susan Cheng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Early Onset ◽  
Cognitive Assessment ◽  
Late Onset ◽  
Montreal Cognitive Assessment ◽  
Digit Symbol Substitution Test ◽  
Digit Symbol ◽  
Symbol Substitution

Hypertension is related to increased risk of cognitive decline in a highly age-dependent manner. However, conflicting evidence exists on the relation between age of hypertension onset and cognition. Our goal was to investigate the association between early- versus late-onset hypertension and midlife cognitive performance in 2946 CARDIA study (Coronary Artery Risk Development in Young Adults) participants (mean age 55±4, 57% women). The participants underwent 9 repeat examinations, including blood pressure measurements, between 1985 to 1986 and 2015 to 2016. The participants underwent brain magnetic resonance imaging and completed Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Stroop interference test, and the Montreal Cognitive Assessment to evaluate cognitive function at the year 30 exam. We assessed the relation between age of hypertension onset and cognitive function using linear regression models adjusted for cognitive decline risk factors, including systolic blood pressure. We observed that individuals with early-onset hypertension (onset at <35 years) had 0.24±0.09, 0.22±0.10, 0.27±0.09, and 0.19±0.07 lower standardized Z-scores in Digit Symbol Substitution Test, Stroop test, Montreal Cognitive Assessment, and a composite cognitive score than participants without hypertension ( P <0.05 for all). In contrast, hypertension onset at ≥35 years was not associated with cognitive function ( P  >0.05 for all). In a subgroup of 559 participants, neither early- nor late-onset hypertension was related to macrostructural brain alterations ( P  >0.05 for all). Our results indicate that early-onset hypertension is a potent risk factor for midlife cognitive impairment. Thus, age of hypertension onset assessment in clinical practice could improve risk stratification of cognitive decline in patients with hypertension.

Piperlongumine activates Sirtuin1 and improves cognitive function in a murine model of Alzheimer’s disease

2018 ◽  
Vol 43 ◽  
pp. 103-111 ◽  
Author(s):  
Jun Go ◽  
Thi-Kim-Quy Ha ◽  
Ji Yeon Seo ◽  
Tae-Shin Park ◽  
Young-Kyoung Ryu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Murine Model ◽  
Model Of Alzheimer’S Disease

scholarly journals L-Norvaline Reverses Cognitive Decline and Synaptic Loss in a Murine Model of Alzheimer’s Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 1036-1054 ◽  
Author(s):  
Baruh Polis ◽  
Kolluru D. Srikanth ◽  
Evan Elliott ◽  
Hava Gil-Henn ◽  
Abraham O. Samson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Murine Model ◽  
Synaptic Loss ◽  
Model Of Alzheimer’S Disease

scholarly journals Social isolation, rather than loneliness, is associated with cognitive decline in older adults: the China Health and Retirement Longitudinal Study

2021 ◽  
pp. 1-8
Author(s):  
Bin Yu ◽  
Andrew Steptoe ◽  
Yongjie Chen ◽  
Xiaohua Jia
Keyword(s):  
Older Adults ◽  
Longitudinal Study ◽  
Cognitive Function ◽  
Episodic Memory ◽  
Cognitive Decline ◽  
Social Isolation ◽  
Mental Status ◽  
Chinese Older Adults ◽  
Confounding Variables

Abstract Background Social isolation and loneliness have each been associated with cognitive decline, but most previous research is limited to Western populations. This study examined the relationships of social isolation and loneliness on cognitive function among Chinese older adults. Methods This study used two waves of data (2011 and 2015) from the China Health and Retirement Longitudinal Study and analyses were restricted to those respondents aged 50 and older. Social isolation, loneliness, and cognitive function were measured at baseline. Follow-up measures on cognitive function were obtained for 7761 participants (mean age = 60.97, s.d. = 7.31; male, 50.8%). Lagged dependent variable models adjusted for confounding factors were used to evaluate the association between baseline isolation, loneliness, and cognitive function at follow-up. Results Loneliness was significantly associated with the cognitive decline at follow-up (episodic memory: β = −0.03, p < 0.01; mental status: β = −0.03, p < 0.01) in the partially adjusted models. These associations became insignificant after additional confounding variables (chronic diseases, health behaviors, disabilities, and depressive symptoms) were taken into account (all p > 0.05). By contrast, social isolation was significantly associated with decreases in all cognitive function measures at follow-up (episodic memory: β = −0.05, p < 0.001; mental status: β = −0.03, p < 0.01) even after controlling for loneliness and all confounding variables. Conclusions Social isolation is associated with cognitive decline in Chinese older adults, and the relationships are independent of loneliness. These findings expand our knowledge about the links between social relationships and the cognitive function in non-Western populations.

Arterial Stiffness Is Associated with White Matter Disruption and Cognitive Impairment: A Community-Based Cohort Study

2021 ◽  
Vol 80 (2) ◽  
pp. 567-576
Author(s):  
Fei Han ◽  
Fei-Fei Zhai ◽  
Ming-Li Li ◽  
Li-Xin Zhou ◽  
Jun Ni ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Arterial Stiffness ◽  
Cognitive Decline ◽  
Sex Education ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
White Matter Injury ◽  
White Matter Integrity ◽  
Cross Sectional

Background: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. Objective: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. Methods: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. Results: Increased baPWV was significantly associated with lower mean global fractional anisotropy (β= –0.118, p < 0.001), higher mean diffusivity (β= 0.161, p < 0.001), axial diffusivity (β= 0.160, p < 0.001), and radial diffusivity (β= 0.147, p < 0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (β= –0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. Conclusion: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.

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