Maternal Immune Activation & AGING

Val's Take/Conjecture

• ​Maternal immune Activation sets into motion a long list of dominoes that reverberate through out the lifespan.​

 

• Further, there is a Trans-Generational aspect to Maternal Immune Activation in which actions of prior generations can affect pregnancies in the present.​

​We don't want to become Eugenicists or Nazis ---

• But we don't want to swing to the other extreme of having a complete inability to recognize developmental differences or gender differences, and the very real consequences those differences can have on the lives of individuals throughout the lifespan.
• ​Maybe we're not saying people are possessed by demons, but we attribute a lot to "Lifestyle Choices."
• That "Lifestyle Choices" hook is meant to be empowering, but many times it is condemning and demonstrably fallacious.

​In Rabbi Kushner's Book -- "When Bad Things Happen to Good People,"   he talks about how a rare aging disease took the life of his son.

​Neurodevelopmental and Psychiatric Disorders are not rare, but they are idiosyncratic --- which can make them hard to see.

Further, Neurodevelopmental and Psychiatric Disorders are premature aging disorders insofar as they involve significant developmental inflammation and dysregulation of multiple systems of the body that will make normal aging very difficult.

Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia  (2025)

​Prenatal immune origins of brain aging differ by sex  (2024)

​Abstract

With an increasing aging population and Alzheimer's disease tsunami, it is critical to identify early antecedents of brain aging to target for intervention and prevention.

Women and men develop and age differently, thus using a sex differences lens can contribute to identification of early risk biomarkers and resilience.

There is growing evidence for fetal antecedents to adult memory impairments, potentially through disruption of maternal prenatal immune pathways.

Here, we hypothesized that in utero exposure to maternal pro-inflammatory cytokines will have sex-dependent effects on specific brain circuitry regulating offspring's memory and immune function that will be retained across the lifespan.

Using a unique prenatal cohort, we tested this in 204 adult offspring, equally divided by sex, who were exposed/unexposed to an adverse in utero maternal immune environment and followed into early midlife (~age 50).

Functional magnetic resonance imaging results showed exposure to pro-inflammatory cytokines in utero (i.e., higher maternal IL-6 and TNF-α levels) was significantly associated with sex differences in brain activity and connectivity underlying memory circuitry and performance and with a hyperimmune state, 50 years later.

In contrast, the anti-inflammatory cytokine, IL-10 alone, was not significantly associated with memory circuitry in midlife.

Predictive validity of prenatal exposure was underscored by significant associations with age 7 academic achievement, also associated with age 50 memory performance.

Results uniquely demonstrated that adverse levels of maternal in utero pro-inflammatory cytokines during a critical period of the sexual differentiation of the brain produced long-lasting effects on immune function and memory circuitry/function from childhood to midlife that were sex-dependent, brain region-specific, and, within women, reproductive stage-dependent.