Format

Send to

Choose Destination
Sleep. 2014 Sep 1;37(9):1489-99. doi: 10.5665/sleep.3998.

In utero exposure to valproic acid changes sleep in juvenile rats: a model for sleep disturbances in autism.

Abstract

STUDY OBJECTIVES:

To determine whether sleep disturbances are found in the valproic acid model of autism spectrum disorders (ASD).

DESIGN:

Comparative study for sleep behavior, sleep architecture, electroencephalogram (EEG) spectral analysis, and glutamic acid decarboxylase (GAD) 65/67 protein expression in juvenile rats exposed to valproic acid (VPA), sodium salt, or saline in utero.

SETTING:

N/A.

PARTICIPANTS:

Juvenile (postnatal day 32) male and female Sprague-Dawley rats.

INTERVENTIONS:

In utero exposure to either saline or 400 mg/kg VPA administered intraperitoneally to the dams on gestational day 12.5. On postnatal days 22-24, all rats were implanted with transmitters to record EEG and electromyogram (EMG) activity.

MEASUREMENTS AND RESULTS:

During the light phase, when nocturnal animals are typically quiescent, the VPA-exposed animals spent significantly more time in wake (∼35 min) and significantly less time in non-rapid eye movement (NREM) sleep (∼26 min) compared to the saline controls. Furthermore, spectral analysis of the EEG revelled that VPA-exposed animals exhibited increased high-frequency activity during wake and rapid eye movement (REM) sleep and reduced theta power across all vigilance states. Interestingly, the gamma-aminobutyric acid (GABA)-ergic system, which modulates the induction and maintenance of sleep states, was also disrupted, with reduced levels of both GAD 65 and GAD67 in the cortical tissue of VPA-exposed animals compared to saline controls.

CONCLUSIONS:

To date, the current animal models of ASD have been underutilized in the investigation of associated sleep disturbances. The VPA animal model recapitulates aspects of sleep disruptions reported clinically, providing a tool to investigate cellular and molecular dysregulation contributing to sleep disruptions in ASD.

KEYWORDS:

autism spectrum disorders; sleep; valproic acid

PMID:
25142574
PMCID:
PMC4153060
DOI:
10.5665/sleep.3998
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center