Item Details

title

BRAIN ANGIOTENSIN MODULATION OF COGNITION AND BEHAVIOR IN MIDDLE-AGED TRANSGENIC RATS

author

Green, Shannon

abstract

The brain renin-angiotensin system (RAS) is increasingly recognized for its role in cognition and behavior, primarily through the actions of angiotensin II (Ang II). However, the impact of altered central Ang II signaling on distinct cognitive domains remains unclear. This study examined two transgenic rat models, (mRen2)27 rats with elevated brain Ang II and ASrAOGEN rats with reduced brain angiotensinogen, compared to Sprague-Dawley (SD) controls during middle age. Animals were tested using touchscreen-based PD and reversal learning (REV) to evaluate associative learning and cognitive flexibility. (mRen2)Twenty-seven rats performed similarly to SD on PD but showed significant deficits in REV. In contrast, ASrAOGEN rats exhibited delayed PD acquisition, failure to meet REV criteria, and lower breakpoints on a progressive ratio (PR) task, reflecting impaired effort-based behaviors. ASrAOGEN rats also showed reduced locomotor activity in the open field test, a phenotype absent in (mRen2)27 animals. Anxiety-like behaviors varied by strain and task, with ASrAOGEN animals showing apathy-like behaviors. These findings suggest that elevated Ang II selectively impairs cognitive flexibility, whereas reduced RAS activity broadly disrupts learning, reinforcement, and movement, supporting brain RAS modulation as a potential therapeutic target for age-related cognitive dysfunction.

subject

Brain angiotensin

cognition

pairwise discrimination

reversal learning

contributor

Chen, Rong (advisor)

Yamaleyeva, Liliya M (committee member)

Gould, Robert W (committee member)

date

2025-06-24T08:36:40Z (accessioned)

2025 (issued)

degree

Neuroscience (discipline)

embargo

2030-05-17 (terms)

2030-05-17 (liftdate)

identifier

http://hdl.handle.net/10339/111055 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis