title: Overexpression of RCAN1 isoform 4 in mouse neurons leads to a moderate behavioral impairment.
abstract: OBJECTIVE
  Recent evidence supports the involvement of RCAN1 in Down syndrome and Alzheimer's disease. To better assess this, we generated and analyzed transgenic mice overexpressing human RCAN1 isoform 4 in neurons.
  
  
  METHODS
  Cognitive behavioral (Morris  water maze, open field, zero maze, elevated plus maze assays); cognitive-associated proteins (CREB, ERK and Tau Western immunoblotting); motor coordination (Rotarod assay); structural abnormalities (immunohistological analyses), and proinflammatory cytokines (cytometric bead assay) were measured  in young (2 month) and old (18 month) transgenics and compared with wild type controls.
  
  
  RESULTS
  In old mice, male but not female transgenics exhibited a significant decrease in anxiety as compared with wild type controls, whereas female but not male transgenic mice exhibited significantly  less motor coordination. No differences were observed in the Morris water maze (spatial learning). pERK levels were reduced in transgenic males but not females, while no differences were observed between genotypes for pCREB and pTau. In young mice, a modest learning and exploratory behavior  was observed in transgenic mice using a limited number of mice, and at higher N values, pCREB and pERK (but not pTau) levels were reduced in transgenics. No macro- and micro-scopic structural abnormalities or proinflammatory cytokine level differences were observed.
  
  
  CONCLUSIONS
  These  results indicate that elevated RCAN1 isoform 4 in neurons leads to a modest cognition-related impairment that is overall stronger at 2 months, suggesting a compensatory adaptation over time. These RCAN1 isoform 4 effects may contribute to at least some of the observed phenotypes in individuals  with Down syndrome and Alzheimer's.
authors: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
authors: Devang L
authors: DL
authors: Bhoiwala
authors: Issam
authors: I
authors: Koleilat
authors: Jiang
authors: J
authors: Qian
authors: Barbara
authors: B
authors: Beyer
authors: Shazaan F
authors: SF
authors: Hushmendy
authors: Alex
authors: A
authors: Mathew
authors: Dipti L
authors: DL
authors: Bhoiwala
authors: Russell J
authors: RJ
authors: Ferland
authors: Dana R
authors: DR
authors: Crawford
mesh_terms: D000367:Age Factors; D000818:Animals; D001526:Behavioral Symptoms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006801:Humans; D006948:Hyperkinesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D045442:Rotarod Performance Test; D018709:Statistics, Nonparametric
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; C108612:RCAN1 protein, human; D010751:Phosphopyruvate Hydratase