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

Background: Early-life adversity impacts on the offspring's brain development and is associated with a higher risk of developing age-associated diseases. In particular, perinatal protein malnutrition appears to be one of the most critical nutritional deficiencies affecting the individual's health and survival, but little is known about its effects on the persistence of behavioral alterations throughout life. Thus, the aim of the present study was to investigate how 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) during gestation 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 four different 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 muscular strength and a reduction in the body weight throughout life. Regarding behavior, while NP mice showed an age-related reduction of exploratory behavior, LP mice showed a constantly low level of this behavior, as well as high anxiety-like behavior, which remained at high levels throughout life. Regarding cognitive functions, LP mice showed deteriorated working memory at middle age. Finally, LP mice died 3.4 times earlier than NP mice. Analysis of the sex-related vulnerability showed that females and males were equally affected by perinatal protein malnutrition throughout life.

Conclusion: Our results demonstrate that perinatal protein malnutrition induces enduring and age-related impairment behaviors, which culminate in higher death risk, affecting males and females equally.