Perinatal protein malnutrition induces the emergence of enduring effects and age-related impairment behaviors, increasing the death risk in a mouse model

FERRONI, NADINA M.; BERARDINO, BRUNO G.; BELLUSCIO, LAURA M.; FERNÁNDEZ, MARÍA S.; FESSER, ESTEFANÍA A.; SONZOGNI, SILVINA V.; CÁNEPA, EDUARDO T.

NUTRITIONAL NEUROSCIENCE

MANEY PUBLISHING

Año: 2020 p. 1 - 14

1028-415X

Background: Early-life adversity impacts on the offspring?s brain development and is associatedwith a higher risk of developing age-associated diseases. In particular, perinatal proteinmalnutrition appears to be one of the most critical nutritional deficiencies affecting theindividual?s health and survival, but little is known about its effects on the persistence ofbehavioral alterations throughout life. Thus, the aim of the present study was to investigatehow perinatal protein malnutrition impacts on age-related changes in the neuromuscular,cognitive and behavioral functions throughout life in a mouse model.Methods: One group of CF-1 dams received a normal-protein diet (NP: 20% casein) duringgestation and lactation, whereas another group received a low-protein diet (LP: 10% casein).The offspring of both groups were analyzed by means of several behavioral tests at fourdifferent ages (young: 6?10 weeks old, mature: 22?26 weeks old, middle age: 39?43 weeks old,and old: 55?59 weeks old).Results: Regarding neuromuscular functions, LP mice showed an early deterioration in muscularstrength and a reduction in the body weight throughout life. Regarding behavior, while NPmice showed an age-related reduction of exploratory behavior, LP mice showed a constantlylow level of this behavior, as well as high anxiety-like behavior, which remained at high levelsthroughout life. Regarding cognitive functions, LP mice showed deteriorated working memoryat middle age. Finally, LP mice died 3.4 times earlier than NP mice. Analysis of the sex-relatedvulnerability showed that females and males were equally affected by perinatal proteinmalnutrition throughout life.Conclusion: Our results demonstrate that perinatal protein malnutrition induces enduring andage-related impairment behaviors, which culminate in higher death risk, affecting males andfemales equally.