# Role of Psychiatric Disease-associated Circular RNAs in Neuronal Function and Cognition

> **NIH NIH R56** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $370,510

## Abstract

PROJECT SUMMARY
Schizophrenia (SCZ) and Bipolar disorder (BD) are heterogeneous psychiatric disorders with severe
socioeconomic impacts and unknown pathogenesis. Circular RNAs (circRNAs) are a novel category of non-
coding RNAs that are derived from the back-splicing and covalent joining of exons and introns of protein-
coding genes, yet lack the capacity to become translated into protein. Recent studies have suggested that
circRNAs are relatively enriched in the brain, are preferentially generated from brain plasticity-associated
genes, and are abundant in dendrites and synapses. However, very little is known about the function of
circRNAs in the human brain and their potential involvement in neuropsychiatric disease. Here we carried out
systematic profiling of circRNA expression in a large cohort of human postmortem brains from subjects with
SCZ and BD and uncovered a subset of differentially expressed circRNAs produced from genes with known
links to synaptic plasticity and neuronal excitability. We propose to study the function of the evolutionary
conserved, neuronal-enriched circRNA, circHomer1, which is reduced in both the prefrontal cortex (PFC) of
both BD and SCZ postmortem brains and in patient-derived neuronal cultures. We hypothesize that
circHomer1 inhibits glutamatergic synaptic transmission and neuronal excitiability via inhibiting the expression
and synaptic localization of plasticity-related Homer protein homolog 1 long isoform B (HOMER1B) mRNA,
thereby disrupting PFC functions. We intend to knockdown circHomer1 expression in both induced pluripotent
stem cell (iPSC)-derived neuronal cultures and mouse PFC and examine its role in neuronal fuction and
psychiatric disease-related behavior. We will test our hypothesis via three specific aims: 1) Test the hypothesis
that circHomer1 and HOMER1B mRNA levels are differentially altered in a cell-specific manner in human PFC
and iPSC-derived neuronal cultures from patients with psychiatric disease. 2) Test the hypothesis that
circHomer1 regulates synaptic efficacy and neuronal excitability through inhibition of HOMER1B localization. 3)
Test the hypothesis that circHomer1 deficits in the PFC influence neuronal firing, cognitive flexibility, and
sensorimotor gating.

## Key facts

- **NIH application ID:** 9883048
- **Project number:** 5R56MH119150-02
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Nikolaos Mellios
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,510
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9883048

## Citation

> US National Institutes of Health, RePORTER application 9883048, Role of Psychiatric Disease-associated Circular RNAs in Neuronal Function and Cognition (5R56MH119150-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9883048. Licensed CC0.

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