# Sex differences in the ability to recover from sleep loss: the roles of development and sex chromosome dosage

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $393,030

## Abstract

Project Summary/Abstract
Sex differences in daily sleep amount, sleep fragmentation, and basal slow wave activity (SWA) are largely
driven by gonadal hormones. However, sex differences in the mid-active phase sleep amount and the ability to
recover from sleep loss are largely insensitive to gonadal hormones, and are regulated in part by sex
chromosomes. Preliminary data in this application show that a key determinant of sex differences in active
phase sleep amount is the presence or absence of the Sry gene of the Y chromosome, which encodes the
testis-determining factor. This study will use two mouse lines with altered sex chromosomes to elucidate the
origin of sex differences in sleep and in order to determine the respective roles of Sry gene and chromosome
complement on sleep regulatory mechanisms. The first specific aim will test the hypothesis that Sry gene
establishes sex differences in sleep homeostasis during development by observing sleep-wake patterns in the
EMG of neonatal, prepubertal mice, and EEG/EMG of adult mice with altered sex chromosomes and
hormones. The second specific aim will test the hypothesis that X chromosome dosage drives sex differences
in the ability to recover from sleep loss. During each of these studies, active-phase sleep amount in mice will
be used as a biomarker for sleep homeostasis. These experiments are important and required to understand
the role of the sleep homeostat in regulating sleep and how it is established. They are the first comprehensive
analysis of sex differences in a juvenile mammalian species and the first to examine the specific effects of
either X or Y chromosome dosage on sleep. The overarching goal of these experiments is to identify the
specific mechanisms through which sex chromosomes and sex-linked genes are able to regulate sleep. These
studies will uncover the origins of sex differences in the homeostatic ability to recover from sleep loss. These
findings will likely lead to improved therapies for sleep disorders that exhibit sex differences in incidence and
severity, particularly those more prevalent in women.

## Key facts

- **NIH application ID:** 10236136
- **Project number:** 2R01NS078410-07A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Ketema N Paul
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $393,030
- **Award type:** 2
- **Project period:** 2012-04-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236136

## Citation

> US National Institutes of Health, RePORTER application 10236136, Sex differences in the ability to recover from sleep loss: the roles of development and sex chromosome dosage (2R01NS078410-07A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10236136. Licensed CC0.

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