WE're Here! The Cellular and Molecular levels of neuro-Developmental & Psychiatric Disorders

Val's Take/Conjecture

• With regard to the Nature vs. Nurture argument --- The National Institute of Mental Health and others have said for awhile --- "IT"S BOTH."
• When we've thought about "NATURE" --- it was generally cast in terms of GENETICS --- but Neuro-Developmental and Psychiatric Disorders were not completely genetic.

It certainly seems today that a big part of the "NATURE" is MATERNAL IMMUNE ACTIVATION and wide-ranging effects from DEVELOPMENTAL INFLAMMATION.

​Trepanation

​Further, how were we really going to know what was going on without opening up someone's skull.

One of the reasons Psychiatry is so far behind other areas of medicine --- they didn't have BIOMARKERS and it wasn't clear how they were ever going to get them.

Well, as it turns out Neuro-Developmental & Psychiatric Disorders are not just brain disorders, and if we know what we're looking for:

• We can get those biomarkers
• Without opening up someone's skull
• Metabolomic biomarkers can be obtained with a  blood draw.

​Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression  (2024)

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​Maternal immune activation imprints translational dysregulation and differential MAP2 phosphorylation in descendant neural stem cells (2025)

​Abstract

Alterations induced by maternal immune activation (MIA) during gestation impact the subsequent neurodevelopment of progeny, a process that in humans, has been linked to the development of several neuropsychiatric conditions.

To undertake a comprehensive examination of the molecular mechanisms governing MIA, we have devised an in vitro model based on neural stem cells (NSCs) sourced from fetuses carried by animals subjected to Poly I:C treatment.

​These neural progenitors demonstrate proliferative capacity and can be effectively differentiated into both neurons and glial cells.

Transcriptomic, proteomic, and phosphoproteomic analyses conducted on these cellular models, in conjunction with counterparts from control treatments, revealed discernible shifts in the expression levels of a specific subset of proteins implicated in neuronal function.

​Furthermore, the phosphoproteomic data highlighted a discernible discrepancy in the basal phosphorylation of proteins between differentiated cells from both experimental groups, particularly within proteins associated with cytoskeletal architecture and synaptic functionality, notably those belonging to the MAP family.

Observed alterations in MAP phosphorylation were found to potentially have functional consequences as they correlate with changes in neuronal plasticity and the establishment of neuronal synapses.

Our data agrees with previous published observations and further underscore the importance of MAP2 phosphorylation state on its function and the impact that this protein has in neuronal structure and function.