Background:
3,4-Methylenedioxymethamphetamine
(MDMA) is still one of the most consumed drugs by adolescents. Its
abuse is related with cognitive impairment, which seems due to
maladaptive plasticity and neural stress. In turn, new hypotheses
suggest that Alzheimer’s disease (AD) may be promoted by neural
stressors.
Aims and methods:
To
test if there is an increase in vulnerability to AD after
chronic MDMA
consumption, we investigated the effects of this drug on recognition
memory and its neurotoxic and neuroplastic effects in a transgenic mouse
model of presymptomatic familiar AD (APP/PS1 dE9, Tg).
Results:
MDMA-treated
animals showed recognition memory deficits, regardless of genotype,
which were accompanied by changes in plasticity markers. Tg mice showed
an impaired expression of
Arc compared with wild-type animals,
but exposure to MDMA induced an increase in the expression of this
factor of the same percentage in both genotypes. However, the expression
of
c-fos, BDNF and p-CREB was not significantly altered by MDMA
treatment in Tg mice. Although Tg mice had higher free choline levels
than wild-type mice (about 123%), MDMA did not modify these levels in
any case, ruling out any specific effect of this drug on the
acetylcholine pathway. MDMA treatment significantly increased the
presence of cortical amyloid plaques, as well as Aβ40, Aβ42 and secreted
APPβ levels in Tg mice. These plaques were accompanied by increased tau
phosphorylation (S199), which does not seem to occur via the canonic
pathway involving AKT, CDK5 or GSK3β.
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