Metformin Treatment Alters Memory Function in a Mouse Model of Alzheimer's Disease

2015 ◽  
Vol 44 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Kacee A. DiTacchio ◽  
Stephen F. Heinemann ◽  
Gustavo Dziewczapolski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Memory Function ◽  
Metformin Treatment ◽  
Model Of Alzheimer’S Disease

Ca2+-permeable TRPV1 pain receptor knockout rescues memory deficits and reduces amyloid-β and tau in a mouse model of Alzheimer’s disease

2019 ◽  
Vol 29 (2) ◽  
pp. 228-237 ◽  
Author(s):  
Juyong Kim ◽  
Siyoung Lee ◽  
Jaekyoon Kim ◽  
Sangwoo Ham ◽  
Jung Han Yoon Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nervous System ◽  
Mouse Model ◽  
Transient Receptor Potential ◽  
Memory Function ◽  
Amyloid Β ◽  
Neuronal Cultures ◽  
Transient Receptor Potential Vanilloid ◽  
Model Of Alzheimer’S Disease

Abstract The transient receptor potential vanilloid 1 (TRPV1) protein is a pain receptor that elicits a hot sensation when an organism eats the capsaicin of red chili peppers. This calcium (Ca2+)-permeable cation channel is mostly expressed in the peripheral nervous system sensory neurons but also in the central nervous system (e.g. hippocampus and cortex). Preclinical studies found that TRPV1 mediates behaviors associated with anxiety and depression. Loss of TRPV1 functionality increases expression of genes related to synaptic plasticity and neurogenesis. Thus, we hypothesized that TRPV1 deficiency may modulate Alzheimer’s disease (AD). We generated a triple-transgenic AD mouse model (3xTg-AD+/+) with wild-type (TRPV1+/+), hetero (TRPV1+/−) and knockout (TRPV1−/−) TRPV1 to investigate the role of TRPV1 in AD pathogenesis. We analyzed the animals’ memory function, hippocampal Ca2+ levels and amyloid-β (Aβ) and tau pathologies when they were 12 months old. We found that compared with 3xTg-AD−/−/TRPV1+/+ mice, 3xTg-AD+/+/TRPV1+/+ mice had memory impairment and increased levels of hippocampal Ca2+, Aβ and total and phosphorylated tau. However, 3xTg-AD+/+/TRPV1−/− mice had better memory function and lower levels of hippocampal Ca2+, Aβ, tau and p-tau, compared with 3xTg-AD+/+/TRPV1+/+ mice. Examination of 3xTg-AD-derived primary neuronal cultures revealed that the intracellular Ca2+ chelator BAPTA/AM and the TRPV1 antagonist capsazepine decreased the production of Aβ, tau and p-tau. Taken together, these results suggested that TRPV1 deficiency had anti-AD effects and promoted resilience to memory loss. These findings suggest that drugs or food components that modulate TRPV1 could be exploited as therapeutics to prevent or treat AD.

scholarly journals Administration of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI Improves Cognitive and Memory Function in the Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Hongwon Kim ◽  
Sumin Kim ◽  
Sang-jun Park ◽  
Gwoncheol Park ◽  
Hakdong Shin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Therapeutic Potential ◽  
Memory Function ◽  
Bifidobacterium Longum ◽  
Bifidobacterium Bifidum ◽  
Pathological Features ◽  
Bdnf Expression ◽  
Model Of Alzheimer’S Disease

Recent evidence indicates that gut microbiota could interact with the central nervous system and affect brain function, including cognition and memory. In this study, we investigated whether Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) alleviated the pathological features in a mouse model of Alzheimer’s disease (AD). Administration of B. bifidum BGN4 and B. longum BORI effectively suppressed amyloidosis and apoptotic processes and improved synaptic plasticity by ameliorating the neuroinflammatory response and BDNF expression. Moreover, behavioral tests indicated that B. bifidum BGN4 and B. longum BORI attenuated the cognitive and memory disability of AD mice. Taken together, the present study highlights the therapeutic potential of B. bifidum BGN4 and B. longum BORI for suppressing the pathological features of AD.

scholarly journals Neutrophil adhesion in brain capillaries contributes to cortical blood flow decreases and impaired memory function in a mouse model of Alzheimer’s disease

2017 ◽  
Author(s):  
Jean C. Cruz Hernández ◽  
Oliver Bracko ◽  
Calvin J. Kersbergen ◽  
Victorine Muse ◽  
Mohammad Haft-Javaherian ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Mouse Model ◽  
Short Term Memory ◽  
Leukocyte Adhesion ◽  
Memory Function ◽  
Model Of Alzheimer’S Disease ◽  
Improved Performance ◽  
Novel Strategy

AbstractThe existence of cerebral blood flow (CBF) reductions in Alzheimer’s disease (AD) patients and related mouse models has been known for decades, but the underlying mechanisms and the resulting impacts on cognitive function and AD pathogenesis remain poorly understood. In the APP/PS1 mouse model of AD we found that an increased number of cortical capillaries had stalled blood flow as compared to wildtype animals, largely due to leukocytes that adhered in capillary segments and blocked blood flow. These capillary stalls were an early feature of disease development, appearing before amyloid deposits. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to an immediate increase in CBF and to rapidly improved performance in spatial and working memory tasks. Our work has thus identified a cellular mechanism that explains the majority of the CBF reduction seen in a mouse model of AD and has also demonstrated that improving CBF rapidly improved short-term memory function. Restoring cerebral perfusion by preventing the leukocyte adhesion that plugs capillaries may provide a novel strategy for improving cognition in AD patients.

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