TY - JOUR
T1 - Effects of prenatal stress exposure on soluble A beta and brain-derived neurotrophic factor signaling in male and female APPswe/PS1dE9 mice
AU - Sierksma, Annerieke S. R.
AU - Vanmierlo, Tim
AU - De Vry, Jochen
AU - Raijmakers, Marjolein E. A.
AU - Steinbusch, Harry W. M.
AU - van den Hove, Daniel L. A.
AU - Prickaerts, Jos
PY - 2012/10
Y1 - 2012/10
N2 - Chronic stress and stress-related disorders, such as major depression (MD), have been shown to increase the risk for developing Alzheimer's disease (AD). Brain-derived neurotrophic factor (BDNF) has been postulated as a neurophysiological link between these illnesses. Our previous research has indicated that exposing the APPswe/PS1dE9 mouse model of AD to prenatal maternal stress (PS) induced a depressive-like phenotype, specifically in female mice. Considering the role of BDNF in depressive-like behavior and its interactions with amyloid-beta (A beta), our aim was to explore whether these mice would also exhibit alterations in soluble A beta, mature BDNF (mBDNF), proBDNF, and the receptors TrkB and p75(NTR) in comparison to non-stressed animals. Our results demonstrate that female APPswe/PS1dE9 mice have higher levels of hippocampal proBDNF and soluble A beta as compared to their male littermates. Additionally, a tendency was observed for PS to lower mBDNF protein levels in the hippocampus, but only in female mice, while receptor levels remained unaltered by sex or PS exposure. Given that female mice both have higher proBDNF and A beta levels, these findings suggest an underlying role for BDNF signaling and A beta production in the selective vulnerability of women for MD and AD development.
AB - Chronic stress and stress-related disorders, such as major depression (MD), have been shown to increase the risk for developing Alzheimer's disease (AD). Brain-derived neurotrophic factor (BDNF) has been postulated as a neurophysiological link between these illnesses. Our previous research has indicated that exposing the APPswe/PS1dE9 mouse model of AD to prenatal maternal stress (PS) induced a depressive-like phenotype, specifically in female mice. Considering the role of BDNF in depressive-like behavior and its interactions with amyloid-beta (A beta), our aim was to explore whether these mice would also exhibit alterations in soluble A beta, mature BDNF (mBDNF), proBDNF, and the receptors TrkB and p75(NTR) in comparison to non-stressed animals. Our results demonstrate that female APPswe/PS1dE9 mice have higher levels of hippocampal proBDNF and soluble A beta as compared to their male littermates. Additionally, a tendency was observed for PS to lower mBDNF protein levels in the hippocampus, but only in female mice, while receptor levels remained unaltered by sex or PS exposure. Given that female mice both have higher proBDNF and A beta levels, these findings suggest an underlying role for BDNF signaling and A beta production in the selective vulnerability of women for MD and AD development.
KW - Brain-derived neurotrophic factor
KW - TrkB
KW - p75(NTR)
KW - Prenatal stress
KW - Alzheimer's disease
KW - APPswe/PS1dE9
U2 - 10.1016/j.neuint.2012.06.022
DO - 10.1016/j.neuint.2012.06.022
M3 - Article
C2 - 22750275
SN - 0197-0186
VL - 61
SP - 697
EP - 701
JO - Neurochemistry International
JF - Neurochemistry International
IS - 5
ER -