Magnetic resonance imaging and spectroscopy in a mouse model of schizophrenia

Abstract

Metabolic brain abnormalities, as demonstrated by 1 H-magnetic resonance spectroscopy techniques, are common occurrences in adult schizophrenia. As mice share important biochemical and genomic similarities with humans, we tested whether brain metabolic abnormalities also occur in a transgenic mouse model of schizophrenia. In vivo 1 H-magnetic resonance spectroscopy at 4.7 T of the chakragati mouse brain revealed abnormalities in relative levels of choline 3.20 ppm and Nacetylaspartate 2.01 ppm compounds. These results are consistent with a prior proposal that deficits in metabolite ratios may be common features of psychotic disorders. Thus, chakragati mice recapitulate certain aspects of the human disease phenotype and further support the utility of this animal model for understanding causal factors underlying uniquely human brain diseases.

Preclinical 1 H-Mrs Neurochemical Profiling in Neurological And Psychiatric Disorders

“…A number of studies have shown the association of reduced NAA levels [81,85,86], increased NAAG levels [85] and reduced Cho levels [87] with disease phenotypes in several brain regions by MRS. Glutamate is also associated with the schizophrenic phenotype; however, the trend is rather complex [88]. Some MRS studies have shown elevated glutamate levels in the prefrontal cortex and dorsomedial striatum (caudate) [89–93], whereas other studies have shown reduced glutamate levels in the anterior cingulate, prefrontal cortex, thalamus and hippocampus [94–98], or no differences in the same brain regions [99–102].…”

“…In these studies, lower GSH levels are associated with schizophrenic symptoms [104-107]. There are two distinct rodent models used to study schizophrenia, one utilizing a genetically modified mouse model, such as a mutant mouse model [87] or a genetic deletion mouse model [107], and the other using pharmacological agents, such as N -methyl- d -aspartate (NMDA) receptor antagonists, to induce schizophrenic phenotypes [93,98]. The chakragati (ckr) mouse is a transgenic insertional mutant that exhibits behavioral abnormalities similar to schizophrenia [108-110].…”

“…The chakragati (ckr) mouse is a transgenic insertional mutant that exhibits behavioral abnormalities similar to schizophrenia [108-110]. The ckr mutant mouse (heterozygous or homozygous) shows elevated Cho:NAA ratios compared with wild-type mice [87] using a PRESS sequence (TR = 1500 ms; TE = 100 ms; 4.7 T). Recently, Duarte et al using SPECIAL (TR = 4s; TE = 2.8 ms; 14.1 T) spectroscopy demonstrated that glutamate-cysteine ligase modifier subunit (GCLM)-null mice – one model of schizophrenia – show reduced GSH levels but increased glutamate, glutamine, NAA, myo -inositol, lactate and alanine levels in the anterior cortex [107].…”

Magnetic Resonance Imaging as a Tool for the Study of Mouse Models of Autism

“…Examples include Huntington's disease [28][29][30][31], Alzheimer's disease [32][33][34], and other mental health diseases like schizophrenia [35,36], and recently, autism [37][38][39]. Genetic knockouts are also examined to identify the role of specific genes in development, behaviour and aging.…”