Amyloid-β (Aβ)
peptides play a significant role in the pathogenesis of
Alzheimer's disease (AD). Neurotoxic effects promoted by Aβ
peptides involve
glutamate transmission impairment, decrease of
neurotrophic factors,
mitochondrial dysfunction, oxidative stress, synaptotoxicity, and neuronal degeneration. Here, we assessed the early events evoked by Aβ1-40 on the hippocampus. Additionally, we sought to unravel the molecular mechanisms of
atorvastatin preventive effect on Aβ-induced hippocampal damage. Mice were treated orally (p.o.) with
atorvastatin 10 mg/kg/day during 7 consecutive days before the intracerebroventricular (i.c.v.) infusion of Aβ1-40 (400 pmol/site). Twenty-four hours after Aβ1-40 infusion, a reduced content of mature
BDNF/proBDNF ratio was observed in Aβ-treated mice. However, there is no alteration in
synaptophysin, PSD-95, and doublecortin immunocontent in the hippocampus. Aβ1-40 promoted an increase in
reactive oxygen species (ROS) and
nitric oxide (NO) generation in hippocampal slices, and
atorvastatin prevented this oxidative burst. Mitochondrial OXPHOS was measured by high-resolution respirometry. At this time point, Aβ1-40 did not alter the O2 consumption rates (OCR) related to phosphorylating state associated with complexes I and II, and the maximal OCR. However,
atorvastatin increased OCR of phosphorylating state associated with complex I and complexes I and II, maximal OCR of complexes I and II, and OCR associated with mitochondrial spare capacity.
Atorvastatin treatment improved mitochondrial function in the rodent hippocampus, even after Aβ infusion, pointing to a promising effect of improving brain mitochondria bioenergetics. Therefore,
atorvastatin could act as an adjuvant in battling the symptoms of AD to preventing or delaying the
disease progression.