Oxidative stress associated with spatial memory impairment and social olfactory deterioration in female mice reveals premature aging aroused by perinatal protein malnutrition

FERRONI, NADINA M.; CHERTOFF, MARIELA J.; ALBERCA, CAROLINA D.; BERARDINO, BRUNO G.; GIANATIEMPO, OCTAVIO; BRAHAMIAN, MARTIN; LEVI, VALERIA; URRUTIA, LEANDRO; FALASCO, GERMÁN; CÁNEPA, EDUARDO T.; SONZOGNI, SILVINA V.

EXPERIMENTAL NEUROLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2023 vol. 368

0014-4886

Early-life adversity, like perinatal protein malnutrition, increases the vulnerability to develop long-term alterationsin brain structures and function. This study aimed to determine whether perinatal protein malnutritionpredisposes to premature aging in a murine model and to assess the cellular and molecular mechanisms involved.To this end, mouse dams were fed either with a normal (NP, casein 20%) or a low-protein diet (LP, casein 8%)during gestation and lactation. Female offspring were evaluated at 2, 7 and 12 months of age. Positron emissiontomography analysis showed alterations in the hippocampal CA3 region and the accessory olfactory bulb of LPmice during aging. Protein malnutrition impaired spatial memory, coinciding with higher levels of reactiveoxygen species in the hippocampus and sirt7 upregulation. Protein malnutrition also led to higher senescenceassociatedβ-galactosidase activity and p21 expression. LP-12-month-old mice showed a higher number ofnewborn neurons that did not complete the maturation process. The social-odor discrimination in LP mice wasimpaired along life. In the olfactory bulb of LP mice, the senescence marker p21 was upregulated, coincidingwith a downregulation of Sirt2 and Sirt7. Also, LP-12-month-old mice showed a downregulation of catalase andglutathione peroxidase, and LP-2-month-old mice showed a higher number of newborn neurons in the subventricularzone, which then returned to normal values. Our results show that perinatal protein malnutritioncauses long-term impairment in cognitive and olfactory skills through an accelerated senescence phenotypeaccompanied by an increase in oxidative stress and altered sirtuin expression in the hippocampus and olfactorybulb.