title: Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice.
abstract: Children with neurofibromatosis type 1 (NF1) are prone to learning and behavioral abnormalities, including problems with spatial learning and attention. The molecular etiology for these deficits is unclear, as previous studies have implicated defective dopamine, cyclic adenosine monophosphate (cAMP), and Ras homeostasis. Using behavioral, electrophysiological, and primary culture, we now demonstrate that reduced dopamine signaling is responsible for cAMP-dependent defects in neuron function and learning. Collectively, these results establish defective dopaminergic function as a contributing factor underlying impaired spatial learning and memory in children and adults with NF1, and support the use of treatments that restore normal dopamine homeostasis for select individuals.
authors.affiliation: Departments of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Diggs-Andrews
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tokuda
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Izumi
authors.forename: Charles F
authors.initials: CF
authors.lastname: Zorumski
authors.forename: David F
authors.initials: DF
authors.lastname: Wozniak
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D000818:Animals; D001288:Attention / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000172:deficiency*; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D007859:Learning Disabilities / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009456:Neurofibromatosis 1 / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D025542:Neurofibromin 1 / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D017557:Ventral Tegmental Area / Q000378:metabolism / Q000503:physiopathology
chemical_list: D025542:Neurofibromin 1; D000242:Cyclic AMP; D004298:Dopamine