scholarly journals Microglial Hyperreactivity Evolved to Immunosuppression in the Hippocampus of a Mouse Model of Accelerated Aging and Alzheimer’s Disease Traits

2021 ◽  
Vol 12 ◽  
Author(s):  
Patricia Molina-Martínez ◽  
Rubén Corpas ◽  
Elisa García-Lara ◽  
Marta Cosín-Tomás ◽  
Rosa Cristòfol ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Inflammatory Cytokines ◽  
Accelerated Aging ◽  
Microglia Activation ◽  
Human Brain Tissue ◽  
Samp8 Mouse ◽  
Pro Inflammatory Cytokines

Neuroinflammation is a risk factor for Alzheimer’s disease (AD). We sought to study the glial derangement in AD using diverse experimental models and human brain tissue. Besides classical pro-inflammatory cytokines, we analyzed chitinase 3 like 1 (CHI3L1 or YKL40) and triggering receptor expressed on myeloid cells 2 (TREM2) that are increasingly being associated with astrogliosis and microgliosis in AD, respectively. The SAMP8 mouse model of accelerated aging and AD traits showed elevated pro-inflammatory cytokines and activated microglia phenotype. Furthermore, 6-month-old SAMP8 showed an exacerbated inflammatory response to peripheral lipopolysaccharide in the hippocampus and null responsiveness at the advanced age (for this strain) of 12 months. Gene expression of TREM2 was increased in the hippocampus of transgenic 5XFAD mice and in the cingulate cortex of autosomal dominant AD patients, and to a lesser extent in aged SAMP8 mice and sporadic early-onset AD patients. However, gene expression of CHI3L1 was increased in mice but not in human AD brain samples. The results support the relevance of microglia activation in the pathways leading to neurodegeneration and suggest diverse neuroinflammatory responses according to the AD process. Therefore, the SAMP8 mouse model with marked alterations in the dynamics of microglia activation and senescence may provide a complementary approach to transgenic mouse models for the study of the neuroinflammatory mechanisms underlying AD risk and progression.

TLR4 Gene Expression and Pro-Inflammatory Cytokines in Alzheimer’s Disease and in Response to Hippocampal Deafferentation in Rodents

2018 ◽  
Vol 63 (4) ◽  
pp. 1547-1556 ◽  
Author(s):  
Justin Miron ◽  
Cynthia Picard ◽  
Josée Frappier ◽  
Doris Dea ◽  
Louise Théroux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Tlr4 Gene ◽  
Pro Inflammatory Cytokines

Lentivirus-Mediated Expression of Human Secreted Amyloid Precursor Protein-Alpha Promotes Long-Term Induction of Neuroprotective Genes and Pathways in a Mouse Model of Alzheimer’s Disease

2020 ◽  
pp. 1-16
Author(s):  
Margaret Ryan ◽  
Valerie T.Y. Tan ◽  
Nasya Thompson ◽  
Diane Guévremont ◽  
Bruce G. Mockett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Integrated Analysis ◽  
Empty Vector ◽  
Mouse Transcriptome

Background: Secreted amyloid precursor protein-alpha (sAPPα) can enhance memory and is neurotrophic and neuroprotective across a range of disease-associated insults, including amyloid-β toxicity. In a significant step toward validating sAPPα as a therapeutic for Alzheimer’s disease (AD), we demonstrated that long-term overexpression of human sAPPα (for 8 months) in a mouse model of amyloidosis (APP/PS1) could prevent the behavioral and electrophysiological deficits that develop in these mice. Objective: To explore the underlying molecular mechanisms responsible for the significant physiological and behavioral improvements observed in sAPPα-treated APP/PS1 mice. Methods: We assessed the long-term effects on the hippocampal transcriptome following continuous lentiviral delivery of sAPPα or empty-vector to male APP/PS1 mice and wild-type controls using Affymetrix Mouse Transcriptome Assays. Data analysis was carried out within the Affymetrix Transcriptome Analysis Console and an integrated analysis of the resulting transcriptomic data was performed with Ingenuity Pathway analysis (IPA). Results: Mouse transcriptome assays revealed expected AD-associated gene expression changes in empty-vector APP/PS1 mice, providing validation of the assays used for the analysis. By contrast, there were specific sAPPα-associated gene expression profiles which included increases in key neuroprotective genes such as Decorin, betaine-GABA transporter, and protocadherin beta-5, subsequently validated by qRT-PCR. An integrated biological pathways analysis highlighted regulation of GABA receptor signaling, cell survival, and inflammatory responses. Furthermore, upstream gene regulatory analysis implicated sAPPα activation of Interleukin-4, which can counteract inflammatory changes in AD. Conclusion: This study identified key molecular processes that likely underpin the long-term neuroprotective and therapeutic effects of increasing sAPPα levels in vivo

SPINGOSINE-1-PHOSPHATE RECEPTOR 5 AGONIST α-971432 IMPROVES LEARNING AND MEMORY IN THE SAMP8 MOUSE MODEL OF ALZHEIMER’S DISEASE

2017 ◽  
Vol 13 (7) ◽  
pp. P949
Author(s):  
Susan A. Farr ◽  
Elizabeth Louise van der Kam ◽  
Jordan W. Brown ◽  
Michael L. Niehoff ◽  
John E. Morley
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Learning And Memory ◽  
Samp8 Mouse ◽  
Model Of Alzheimer’S Disease

O5-04-03: AMYLIN TREATMENT AMELIORATES ABNORMAL PATTERNS OF GENE EXPRESSION IN THE CEREBRAL CORTEX OF AN ALZHEIMER’S DISEASE MOUSE MODEL

2016 ◽  
Vol 12 ◽  
pp. P386-P386
Author(s):  
Erming Wang ◽  
Haihao Zhu ◽  
Adam Gower ◽  
Jan Krzysztof Blusztajn ◽  
Neil W. Kowall ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Cortex ◽  
Mouse Model

P3-193: METFORMIN INCREASES PKC AND DECREASES APP AND TAU IN THE SAMP8 MOUSE MODEL OF ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_21) ◽  
pp. P1141-P1141
Author(s):  
John E. Morley ◽  
Michael L. Niehoff ◽  
Elizabeth C. Roesler ◽  
Susan A. Farr
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Samp8 Mouse ◽  
Model Of Alzheimer’S Disease

scholarly journals Alzheimer's disease and periodontitis - an elusive link

2014 ◽  
Vol 60 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Abhijit N. Gurav
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Critical Role ◽  
Anaerobic Bacteria ◽  
Systemic Infection ◽  
Low Grade ◽  
Inflammatory Status ◽  
Pro Inflammatory Cytokines

Alzheimer's disease is the preeminent cause and commonest form of dementia. It is clinically characterized by a progressive descent in the cognitive function, which commences with deterioration in memory. The exact etiology and pathophysiologic mechanism of Alzheimer's disease is still not fully understood. However it is hypothesized that, neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Alzheimer's disease is marked by salient inflammatory features, characterized by microglial activation and escalation in the levels of pro-inflammatory cytokines in the affected regions. Studies have suggested a probable role of systemic infection conducing to inflammatory status of the central nervous system. Periodontitis is common oral infection affiliated with gram negative, anaerobic bacteria, capable of orchestrating localized and systemic infections in the subject. Periodontitis is known to elicit a "low grade systemic inflammation" by release of pro-inflammatory cytokines into systemic circulation. This review elucidates the possible role of periodontitis in exacerbating Alzheimer's disease. Periodontitis may bear the potential to affect the onset and progression of Alzheimer's disease. Periodontitis shares the two important features of Alzheimer's disease namely oxidative damage and inflammation, which are exhibited in the brain pathology of Alzheimer's disease. Periodontitis can be treated and hence it is a modifiable risk factor for Alzheimer's disease.

A Serial Analysis of Gene Expression Profile of the Alzheimer’s Disease Tg2576 Mouse Model

2009 ◽  
Vol 17 (4) ◽  
pp. 360-379 ◽  
Author(s):  
Amee J. George ◽  
Lavinia Gordon ◽  
Tim Beissbarth ◽  
Irene Koukoulas ◽  
R. M. Damian Holsinger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Tg2576 Mouse
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