# Project 2

> **NIH NIH P50** · JOHNS HOPKINS UNIVERSITY · 2020 · $466,696

## Abstract

The main goal of the current proposal is to identify the molecular and neurobehavioral abnormalities in young
adulthood resulting from the genetic mutations of the microtubule-related genes associated with schizophrenia
(SZ), such as PCM1, DPYSL2, and 16p11 copy number variations (CNVs), and how these alterations can be
exacerbated by adolescent social isolation to produce a full-blown psychiatric disorder in young adulthood. We
hypothesize that mice with the microtubule-associated genetic mutations will display stress-related molecular
alterations and abnormal prefrontal cortex (PFC) maturation during adolescence and/or young adulthood,
leading to adult behavioral phenotypes resembling different dimensions of SZ. Aim 1 will identify the genetic
mutations-produced neurobehavioral abnormalities that can be exacerbated by adolescent social isolation in
mice. We will identify the effects of the genetic risk factors on SZ-related behaviors as well as maturation of
GABAergic interneurons and dendritic spines of pyramidal neurons in the PFC. We will also examine if these
phenotypes are exacerbated by adolescent social isolation. Aim 2 will determine the genetic mutations-
produced molecular changes that can be intensified by adolescent social isolation. Specifically, we will
evaluate expression of the candidate stress-related factors and the global transcriptome changes in PFC. Aim
3 will identify alterations in stress-associated molecules in peripheral blood samples collected from two
independent prospective cohorts and compare the human results with those from the mouse models. The
project will determine alteration in stress-related molecular expression induced by genetic mutations, leading to
impaired PFC maturation during adolescence and adult behavioral consequences, which may underlie
susceptibility to detrimental effects of adolescent social isolation. Our project will facilitate future development
of prognostic measures and biomarkers to help identify prodromal signs of the disease.

## Key facts

- **NIH application ID:** 9978139
- **Project number:** 5P50MH094268-10
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Mikhail V Pletnikov
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $466,696
- **Award type:** 5
- **Project period:** 2011-07-12 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978139

## Citation

> US National Institutes of Health, RePORTER application 9978139, Project 2 (5P50MH094268-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9978139. Licensed CC0.

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