title: Perfusion single photon emission computed tomography in a mouse model of neurofibromatosis type 1: towards a biomarker of neurologic deficits.
abstract: Neurofibromatosis type 1 (NF1) is a single-gene disorder affecting neurologic function in humans. The NF1+/- mouse model with germline mutation of the NF1 gene presents with deficits in learning, attention, and motor coordination, very similar to NF1 patients. The present study performed brain perfusion single-photon emission computed tomography (SPECT) in NF1+/- mice to identify possible perfusion differences as surrogate marker for altered cerebral activity in NF1. Cerebral perfusion was measured with hexamethyl-propyleneamine oxime (HMPAO) SPECT in NF1+/- mice and their wild-type littermates longitudinally at juvenile age and at young adulthood. Histology and immunohistochemistry were performed to test for structural changes. There was increased HMPAO uptake in NF1 mice in the amygdala at juvenile age, which reduced to normal levels at young adulthood. There was no genotype effect on thalamic HMPAO uptake, which was confirmed by ex vivo measurements of F-18-fluorodeoxyglucose uptake in the thalamus. Morphologic analyses showed no major structural abnormalities. However, there was some evidence of increased density of microglial somata in the amygdala of NF1-deficient mice. In conclusion, there is evidence of increased perfusion and increased density of microglia in juvenile NF1 mice specifically in the amygdala, both of which might be associated with altered synaptic plasticity and, therefore, with cognitive deficits in NF1.
authors.affiliation: 1] Department of Nuclear Medicine, University Medicine Charité Berlin, Berlin, Germany [2] Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Ivayla
authors.initials: I
authors.lastname: Apostolova
authors.affiliation: Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Niedzielska
authors.affiliation: Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Derlin
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Eva J
authors.initials: EJ
authors.lastname: Koziolek
authors.affiliation: Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Amthauer
authors.affiliation: Neuroscience Research Center, University Medicine Charité Berlin, Berlin, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Salmen
authors.affiliation: 1] Department of Neuropathology, Oslo University Hospital (OUS), University of Oslo (UiO), Oslo, Norway [2] LIED, University of Lübeck, Lübeck, Germany [3] Leibniz Institute of Plant Biochemistry, Halle, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Pahnke
authors.affiliation: Department of Nuclear Medicine, University Medicine Charité Berlin, Berlin, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Brenner
authors.affiliation: Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Victor F
authors.initials: VF
authors.lastname: Mautner
authors.affiliation: Department of Nuclear Medicine, University Medicine Charité Berlin, Berlin, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Buchert
mesh_terms: D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D051379:Mice; D008817:Mice, Mutant Strains; D009456:Neurofibromatosis 1 / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D025542:Neurofibromin 1 / Q000235:genetics / Q000378:metabolism; D010091:Oximes / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods*; D011859:Radiography
chemical_list: D025542:Neurofibromin 1; D010091:Oximes; C068296:hexamethylpropyleneamine oxime