Striatal Magnetic Resonance Spectroscopy Abnormalities in Young Adult Sapap3 Knockout Mice

Abstract

BackgroundObsessive-compulsive disorder (OCD) is a debilitating condition with lifetime prevalence of 1% to 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 obsessive-compulsive and related disorders. KO mice exhibit compulsive self-grooming behavior analogous to behaviors found in people with obsessive-compulsive and related disorders. Striatal hyperactivity has been reported in these mice and in humans with OCD. MethodsStriatal 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. ResultsYoung adult KO mice had lower striatal lactate (p = .006) and glutathione (p = .039) levels. Among all mice, striatal lactate and glutathione levels were associated (r = .73, p = .007). We found no group differences in medial frontal cortex metabolites. At the age range studied, only one of eight KO mice had skin lesions indicative of severe compulsive grooming. ConclusionsYoung adult Sapap3 KO mice have striatal but not medial frontal cortex magnetic resonance spectroscopy abnormalities that may reflect striatal hypermetabolism accompanied by oxidative stress. These abnormalities typically precede the onset of severe compulsive grooming. Our findings are consistent with striatal hypermetabolism in OCD. Together, these results suggest that striatal magnetic resonance spectroscopy measures of lactate or glutathione might be useful biomarkers for early detection of risk for developing compulsive behavior disorders.