"Resilience," The Immune System & "Second Hits"

​Val's Take/Conjecture

• "Maternal Immune Activation" involves the Immune System and occurs In Utero.
• Among other things, Maternal Immune Activation impacts Adult Behavior.
• So the first hit is "Maternal Immune Activation."
• But during the course of our lives we have many and varied experiences of INFLAMMATION and STRESS.
• It's a BRAVE NEW WORLD out there and some researchers are already proposing:
  • "immunomodulatory" treatments for depression, and
  • targeting microglia in treatment efforts.
• The point I want to make is that when we talk about "RESILENCE" --- there are actually very complicated mechanics to that.

Additionally, UNPREDICTED CHRONIC STRESS seems to be an issue for mammals and us.

• The Unpredictability of Neuro-Developmental and Psychiatric Disorders is taking a huge toll on Individuals, Families, Communities and Societies.
• There is CONSCIOUS AWARENESS of the need for:
  • Updated Paradigms
  • Biomarkers, and
  • Better Treatments that address Multi-System Disorders

​Genes Participating in the Ensheathment of Neurons Are Affected by Postnatal Stress and Maternal Immune Activation in the Pituitary Gland (2023)

​Fetal brain response to maternal inflammation requires microglia
​ (2024)

In utero infection and maternal inflammation can adversely impact fetal brain development.

Maternal systemic illness, even in the absence of direct fetal brain infection, is associated with an increased risk of neuropsychiatric disorders in affected offspring. . .

Using a rodent maternal immune activation (MIA) model in which polyinosinic:polycytidylic acid is injected into pregnant mice, we demonstrate long-lasting transcriptional changes in fetal microglia that persist into postnatal life.

We find that MIA induces widespread gene expression changes in neuronal and non-neuronal cells; importantly, these responses are abolished by selective genetic deletion of microglia, indicating that microglia are required for the transcriptional response of other cortical cell types to MIA.

These findings demonstrate that microglia play a crucial durable role in the fetal response to maternal inflammation, and should be explored as potential therapeutic cell targets.

The inflammatory underpinning of depression: An historical perspective (2024)

​"Synthesizing insights from this extensive research, the review presents an integrative model of the biological foundations of inflammation-associated depression.

"It posits that we have reached a critical juncture where the translation of this knowledge into personalized immunomodulatory treatments for depression is not just possible, but imperative."