3xTgAD mice exhibit altered behavior and elevated A<script type="math/tex">\beta</script> after chronic mild social stress

Rothman, Sarah M.; Herdener, Nathan; Camandola, Simonetta; Texel, Sarah J.; Mughal, Mohamed R.; Cong, Wei-Na; Martin, Bronwen; Mattson, Mark P.

doi:10.1016/J.NEUROBIOLAGING.2011.07.005

Title

3xTgAD mice exhibit altered behavior and elevated A $\beta$ after chronic mild social stress

Author

Rothman, Sarah M.

Herdener, Nathan

Camandola, Simonetta

Texel, Sarah J.

Mughal, Mohamed R.

Cong, Wei-Na

Martin, Bronwen

Mattson, Mark P.

Abstract

Chronic stress may be a risk factor for developing Alzheimers disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety and hippocampal Aβ, ptau and BDNF levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6 week stress period 3xTgAD mice displayed increased anxiety, elevated levels of Aβ oligomers and intraneuronal Aβ, and decreased BDNF levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates Aβ accumulation and impairs neurotrophic signaling.

Language

English

Source (journal)

Neurobiology of aging. - Fayetteville, N.Y.

Publication

Fayetteville, N.Y. : 2012

ISSN

0197-4580

DOI

10.1016/J.NEUROBIOLAGING.2011.07.005

Volume/pages

33 :4 (2012) , p. 1-12