Overexpression of RCAN1 isoform 4 in mouse neurons leads to a moderate behavioral impairment

Devang L. Bhoiwala, Issam Koleilat, Jiang Qian, Barbara Beyer, Shazaan F. Hushmendy, Alex Mathew, Dipti L. Bhoiwala, Russell J. Ferland, Dana R. Crawford

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objectives: 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 proinflammatorycytokine level differences were observed. Discussion: These results indicate that elevated RCAN1 isoform 4 in neurons leads to a modest cognitionrelated 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.

Original languageEnglish (US)
Pages (from-to)79-89
Number of pages11
JournalNeurological Research
Volume35
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Fingerprint

Transgenic Mice
Protein Isoforms
Down Syndrome
Neurons
Rotarod Performance Test
Maze Learning
tau Proteins
Cyclic AMP Response Element-Binding Protein
Exploratory Behavior
Water
Alzheimer Disease
Anxiety
Western Blotting
Genotype
Learning
Cytokines
Phenotype
Spatial Learning

Keywords

  • Alzheimer's
  • Cognitive impairment
  • Down syndrome
  • Neuronal expression
  • RCAN1

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Overexpression of RCAN1 isoform 4 in mouse neurons leads to a moderate behavioral impairment. / Bhoiwala, Devang L.; Koleilat, Issam; Qian, Jiang; Beyer, Barbara; Hushmendy, Shazaan F.; Mathew, Alex; Bhoiwala, Dipti L.; Ferland, Russell J.; Crawford, Dana R.

In: Neurological Research, Vol. 35, No. 1, 01.2013, p. 79-89.

Research output: Contribution to journalArticle

Bhoiwala, DL, Koleilat, I, Qian, J, Beyer, B, Hushmendy, SF, Mathew, A, Bhoiwala, DL, Ferland, RJ & Crawford, DR 2013, 'Overexpression of RCAN1 isoform 4 in mouse neurons leads to a moderate behavioral impairment', Neurological Research, vol. 35, no. 1, pp. 79-89. https://doi.org/10.1179/1743132812Y.0000000117
Bhoiwala, Devang L. ; Koleilat, Issam ; Qian, Jiang ; Beyer, Barbara ; Hushmendy, Shazaan F. ; Mathew, Alex ; Bhoiwala, Dipti L. ; Ferland, Russell J. ; Crawford, Dana R. / Overexpression of RCAN1 isoform 4 in mouse neurons leads to a moderate behavioral impairment. In: Neurological Research. 2013 ; Vol. 35, No. 1. pp. 79-89.
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