title: [Evaluation of imaging biomarker by transgenic mouse models].
abstract: The invention of trangenic and gene knockout mice contributes to the understanding of various brain functions. With the previous-generation positron emission tomography (PET) camera it was impossible to visualize the mouse brain functions, while the newly developed small-animal PET camera with higher resolution is enough to visualize the mouse brain functions. In the present study, we investigated the visualization of functional brain images for a few transgenic mouse models using the small-animal PET. In neurodegenerative illnesses such as Alzheimer disease (AD), the relationship between etiopathology and main symptoms has been elucidated relatively well; therefore several transgenic mice have been already developed. We succeeded in visualizing amyloid images in human mutant amyloid precursor protein (APP) transgenic mice brains. This result suggested that small-animal PET enabled the quantitative analysis of pathologies in the Tg mouse brain. Psychiatric disorders are presumed to have underlying multiple neural dysfunctions. Despite some efficient medicinal therapies having been already established, the etiopathology of mental illness and its biological markers have not been clarified. Thus, we investigated in type II Ca-calmodulin-dependent protein kinase alpha (CaMKII alpha) heterozygous knockout (hKO) mouse, a major protein kinase in the brain. The CaMKII alpha hKO mice have several abnormal behavioral phenotypes, such as hyper aggression and lack of anxiogenic responses; therefore CaMKII alpha might involve in the pathogenesis of mood disorder and affect personal characterizations. Furthermore, serotonin (5-HT) 1A receptor density in the CaMKII alpha hKO mouse brain changed among various brain regions compared to wild mice. These mechanistic insights, PET assays of Tg mice that we have established here, provide an efficient methodology for preclinical evaluation of emerging diagnostic and therapeutic agents for neurodegenerative and psychiatric illnesses.
authors: Brain Imaging Project, National Institute of Radiological Sciences, 9-1, Anagawa 4-chome, Inage-ku, Chiba, 263-8555 Japan. jun@nirs.go.jp
authors: Jun
authors: J
authors: Maeda
authors: Makoto
authors: M
authors: Higuchi
authors: Tetsuya
authors: T
authors: Suhara
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism* / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019964:Mood Disorders / Q000209:etiology; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000209:etiology; D049268:Positron-Emission Tomography / Q000379:methods*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D044282:Receptor, Serotonin, 5-HT1A; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2