Striatal magnetic resonance spectroscopy abnormalities in young adult SAPAP3 knockout mice.

Biol Psychiatry Cogn Neurosci Neuroimaging
Authors
Abstract

BACKGROUND: Obsessive compulsive disorder (OCD) is a debilitating condition with lifetime prevalence of 1-3%. OCD typically arises in youth but delays in diagnosis impede optimal treatment and developmental studies of the disorder. Research using genetically modified rodents may provide models of etiology that enable earlier detection and intervention. The SAPAP3 knockout (KO) transgenic mouse was developed as an animal model of OCD and related disorders (OCRD). KO mice exhibit compulsive self-grooming behavior analogous to behaviors found in people with OCRD. Striatal hyperactivity has been reported in these mice and in humans with OCD.

METHODS: Striatal and medial frontal cortex 9.4 Tesla proton spectra were acquired from young adult SAPAP3 KO and wild-type control mice to determine whether KO mice have metabolic and neurochemical abnormalities.

RESULTS: Young adult KO mice had lower striatal lactate (P=0.006) and glutathione (P=0.039) levels. Among all mice, striatal lactate and glutathione levels were associated (R=0.73, P=0.007). We found no group differences in medial frontal cortex metabolites. At the age range studied, only 1 of 8 KO mice had skin lesions indicative of severe compulsive grooming.

CONCLUSION: Young adult SAPAP3 KO mice have striatal but not medial frontal cortex MRS abnormalities that may reflect striatal hypermetabolism accompanied by oxidative stress. These abnormalities typically preceded the onset of severe compulsive grooming. Our findings are consistent with striatal hypermetabolism in OCD. Together, these results suggest that striatal MRS measures of lactate or glutathione might be useful biomarkers for early detection of risk for developing compulsive behavior disorders.

Year of Publication
2016
Journal
Biol Psychiatry Cogn Neurosci Neuroimaging
Volume
1
Issue
1
Pages
39-48
Date Published
2016 Jan 01
ISSN
2451-9030
DOI
10.1016/j.bpsc.2015.10.001
PubMed ID
26858992
PubMed Central ID
PMC4742338
Links
Grant list
S10 RR019356 / RR / NCRR NIH HHS / United States