Title:Influence of Genetic Background on Apathy-Like Behavior in Triple Transgenic AD Mice
VOLUME: 13 ISSUE: 8
Author(s):R. Pardossi-Piquard, I. Lauritzen, C. Bauer, G. Sacco, P. Robert and F. Checler
Affiliation:IPMC, UMR7275 CNRS/UNS, Laboratory of Excellence DistALZ, 660 route des Lucioles, 0660 Valbonne, France.
Keywords:Apathy, behavior, C99, LTP, immunohistochemistry, triple transgenic mice, genetic background.
Abstract:Apathy is an early and common neuropsychiatric syndrome in Alzheimer’s disease (AD)
patients. In clinical trials, apathy is associated with decreased motor activity that can be monitored by
actigraphy. The triple transgenic mouse AD model (3xTgAD) has been shown to recapitulate the biochemical
lesions as well as many of the synaptic and cognitive alterations associated with AD. In the
present work we found that these mice also develop an early and consistent apathy-like behavior as
evidenced by a drastic decrease in spontaneous activity measured by actimetry. We recently established
that these mice also display an intraneuronal accumulation of the β-secretase-derived βAPP fragment (C99) appearing
early, in absence of Aβ. Interestingly, we found that the apathy-like behavior observed in 3xTgAD mice was temporally
associated with C99 accumulation and synaptic alterations. Since it is well known that the genetic background can
strongly influence behavior and can induce transcriptional variability in animal models, we decided to determine the influence
of genetic background on the above-described alterations. We backcrossed 3xTgAD mice to C57BL/6 and found
that the genetic background had no influence on either C99 accumulation or synaptic plasticity alterations, but strongly affected
the apathy-like behavior.
