Limited impact of social isolation on Alzheimer-like symptoms in a triple transgenic mouse model.

Abstract

Gene-environment interactions are known to play a major role in the ethiopathology of several neuropsychiatric disorders, including Alzheimer's disease (AD). The present study investigates whether environmental manipulations, that is, social isolation, may affect the genetic predisposition to develop AD-related traits in a triple transgenic mouse model (3 x Tg-AD), as suggested by our previous study employing physical exercise (Pietropaolo et al., 2008). Mutant and wild type mice of both sexes were housed singly or in groups from weaning, and evaluated behaviorally at 6 to 7 months of age. Independent of sex, the 3 x Tg-AD genotype was associated with enhanced acoustic startle response, improved performance in the cued version of the water maze and a clear impairment in the Y maze. Notably, the female (but not male) mutant mice showed increased anxiety. Although social isolation was effective in modifying several behaviors, it did not exacerbate any of the AD-like symptoms. Our findings demonstrated the differential susceptibility of the 3 x Tg-AD mouse line to environmental manipulations, showing that social isolation did not induce remarkable effects on the genetically determined AD-like symptoms, in contrast to what previously observed with physical exercise.

Aligning physiology with psychology: Translational neuroscience in neuropsychiatric drug discovery

“…Similar effects of environmental enrichment in APP/PS1 on beta amyloid levels and deposits were reported by Lazarov and colleagues (Lazarov et al, 2005). These results suggest that the effects of environmental enrichment on amyloid metabolism may be transgenic specific [see also, (Pietropaolo et al, 2009).…”

Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

“…This notion of increased anxiety is further supported by the evidence of early enhancements in innate-and conditioned-fear responses [57]. Along the same line, group-housed 6 month-old 3xTg-AD mice showed enhanced acoustic startle response, reduced locomotion in the open-field, and impaired spontaneous alternation in the Y-maze [58]. As in our water maze, they showed normal retention and “cognitive” impairment limited to the Y-maze test.…”

APP transgenic mice for modelling behavioural and psychological symptoms of dementia (BPSD)

“…As expected, hypoactivity in the open-field has been described in several models, including two mutations with the Swedish mutation, APP 751 SWE (as cited in the previous subsection) (Lalonde et al, 2002b; Van Dam et al, 2003) and APP 770 SWE (Moechars et al, 1999b), one with the London mutation, APP 695 LD (Moechars et al, 1999b), and one with both Swedish and London mutations, APP 751 SWE/LD (Blanchard et al, 2009), together with four multigenic models, namely APP 695 SWEch+ PS1 /A246E (Liu et al, 2002), APP 751 SWE/LD+ PS1 /M146L (Le Cudennec et al, 2008), APP 695 SWE+ PS1 /M146L/ Thy1 (Pugh et al, 2007), and 3xTg-AD (Arsenault et al, 2011; Gulinello et al, 2009; Halagappa et al, 2007; Nelson et al, 2007; Pietropaolo et al, 2009). Also as expected, in view of findings with the hyperactive phenotype, this pattern appears age-related, at least with respect to APP 695 SWE+ PS1 /M146L/ Thy1 mutants, found to be hypoactive at 10 months of age (Pugh et al, 2007) but not at 4 (Pardon et al, 2009).…”