Dysregulated Gut Homeostasis Observed Prior to the Accumulation of the Brain Amyloid-β in Tg2576 Mice

Autor: Akihiko Urayama, Meenakshi B. Bhattacharjee, Pedram Honarpisheh, Caroline R. Reynolds, Nagireddy Putluri, Louise D. McCullough, Jose Felix Moruno Manchon, Bhanu P. Ganesh, Maria P. Blasco Conesa
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Vascular Endothelial Growth Factor A
inflammatory cytokines
Plaque
Amyloid
Pathogenesis
lcsh:Chemistry
Mice
Myelin
0302 clinical medicine
neurodegenerative diseases
Intestinal Mucosa
lcsh:QH301-705.5
Spectroscopy
Mice
Inbred BALB C
0303 health sciences
Tight junction
gut-brain axis
amyloid
alzheimer’s disease
General Medicine
3. Good health
Computer Science Applications
Vitamin B 12
medicine.anatomical_structure
tight junction proteins
Female
medicine.symptom
medicine.medical_specialty
Amyloid
Gut–brain axis
Mice
Transgenic
Inflammation
Article
Catalysis
Proinflammatory cytokine
Inorganic Chemistry
03 medical and health sciences
tg2576
Internal medicine
mental disorders
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
030304 developmental biology
gut integrity
Amyloid beta-Peptides
business.industry
Organic Chemistry
Interleukin-9
Cubilin
Gastrointestinal Microbiome
Chemokine CXCL10
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
business
030217 neurology & neurosurgery
b12
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 5, p 1711 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 5
ISSN: 1422-0067
Popis: Amyloid plaques in Alzheimer&rsquo
s disease (AD) are associated with inflammation. Recent studies demonstrated the involvement of the gut in cerebral amyloid-beta (A&beta
) pathogenesis
however, the mechanisms are still not well understood. We hypothesize that the gut bears the A&beta
burden prior to brain, highlighting gut&ndash
brain axis (GBA) interaction in neurodegenerative disorders. We used pre-symptomatic (6-months) and symptomatic (15-months) Tg2576 mouse model of AD compared to their age-matched littermate WT control. We identified that dysfunction of intestinal epithelial barrier (IEB), dysregulation of absorption, and vascular A&beta
deposition in the IEB occur before cerebral A&beta
aggregation is detectible. These changes in the GBA were associated with elevated inflammatory plasma cytokines including IL-9, VEGF and IP-10. In association with reduced cerebral myelin tight junction proteins, we identified reduced levels of systemic vitamin B12 and decrease cubilin, an intestinal B12 transporter, after the development of cerebral A&beta
pathology. Lastly, we report A&beta
deposition in the intestinal autopsy from AD patients with confirmed cerebral A&beta
pathology that is not present in intestine from non-AD controls. Our data provide evidence that gut dysfunction occurs in AD and may contribute to its etiology. Future therapeutic strategies to reverse AD pathology may involve the early manipulation of gut physiology and its microbiota.
Databáze: OpenAIRE
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