# Gut dysbiosis and 5-HT2A dysregulation in a preclinical schizophrenia model

> **NIH NIH F30** · VIRGINIA COMMONWEALTH UNIVERSITY · 2021 · $38,622

## Abstract

Project Summary/Abstract
The pathophysiology of schizophrenia is complex and, despite significant advances in understanding the
development of this disorder, available treatments will not produce a response in a significant subset of patients.
This fact, combined with the significant morbidity associated with currently available antipsychotics, highlights a
need for novel approaches to understanding schizophrenia pathophysiology and developing new treatments.
The gut microbiome has emerged as a contributor to neuropsychiatric disorders in humans and behavioral
alterations in rodents, but has not been extensively investigated within the context of schizophrenia. Interestingly,
the microbiome has been demonstrated to affect expression of the serotonin 5-HT2A receptor, which has been
well implicated within human schizophrenia as well as animal models of the disorder. Our group has
demonstrated that both antipsychotic-free postmortem samples from human schizophrenia patients and
offspring mice within a maternal immune activation model of schizophrenia display increased density of the
receptor in the prefrontal cortex. Mice within this model also display increased rates of the psychosis-like, 5-HT2A
receptor-dependent head twitch response. Other groups have demonstrated association of the receptor with
schizophrenia-related phenotypes such as altered function of cortical pyramidal neurons and sensorimotor gating
deficits. We therefore propose to investigate the role of the gut microbiome in the development of 5-HT2A receptor
alterations and subsequent schizophrenia-like phenotypes in an influenza virus-induced maternal immune
activation model of schizophrenia in mice. Transgenic mice, molecular biology techniques, rodent behavioral
assays, and microscopy will be used to accomplish these goals. Our results have the potential to further
understanding of the pathophysiology of schizophrenia and implication of the gut microbiome in schizophrenia
would allow for investigation into new targets for therapy and prevention.
The training plan proposes to develop the applicant’s scientific and clinical abilities via introduction to
experimental techniques relevant to molecular biology, mouse behavior, dendritic spine analysis, and
manipulation of the gut microbiome; development of essential skills such as scientific communication, statistical
analysis, hypothesis generation and testing, and ethics; enhancement of clinical skills during medical school
clerkships; and addition of scientific knowledge through venues such as seminars and journal clubs. The
environment in which the proposed research will take place possesses the equipment necessary to conduct the
work, a wealth of core facilities including the Microscopy and Transgenic Mouse cores, and faculty with expertise
in a breadth of areas including psychiatric genetics, microscopy, and neuroscience.

## Key facts

- **NIH application ID:** 10242023
- **Project number:** 5F30MH116550-04
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Justin M Saunders
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,622
- **Award type:** 5
- **Project period:** 2018-09-10 → 2022-09-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242023

## Citation

> US National Institutes of Health, RePORTER application 10242023, Gut dysbiosis and 5-HT2A dysregulation in a preclinical schizophrenia model (5F30MH116550-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242023. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*