Correlation between orphan nuclear receptor Nurr1 expression and amyloid deposition in 5XFAD mice, an animal model of Alzheimer's disease

Minho Moon; Inhye Jeong; Chun-Hyung Kim; Jihong Kim; Paula K J Lee; Inhee Mook-Jung; Pierre Leblanc; Kwang-Soo Kim

doi:10.1111/jnc.12935

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Correlation between orphan nuclear receptor Nurr1 expression and amyloid deposition in 5XFAD mice, an animal model of Alzheimer's disease

Journal article

Open access

Peer reviewed

Correlation between orphan nuclear receptor Nurr1 expression and amyloid deposition in 5XFAD mice, an animal model of Alzheimer's disease

Minho Moon, Inhye Jeong, Chun-Hyung Kim, Jihong Kim, Paula K J Lee, Inhee Mook-Jung, Pierre Leblanc and Kwang-Soo Kim

Journal of neurochemistry, Vol.132(2), pp.254-262

01/2015

DOI: 10.1111/jnc.12935

PMCID: PMC4301994

PMID: 25156412

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Abstract

The functional roles of the orphan nuclear receptor, Nurr1, have been extensively studied and well established in the development and survival of midbrain dopamine neurons. As Nurr1 and other NR4A members are widely expressed in the brain in overlapping and distinct manners, it has been an open question whether Nurr1 has important function(s) in other brain areas. Recent studies suggest that up-regulation of Nurr1 expression is critical for cognitive functions and/or long-term memory in forebrain areas including hippocampal formation. Questions remain about the association between Nurr1 expression and Alzheimer's disease (AD) brain pathology. Here, using our newly developed Nurr1-selective antibody, we report that Nurr1 protein is prominently expressed in brain areas with Aβ accumulation, that is, the subiculum and the frontal cortex, in the 5XFAD mouse and that Nurr1 is highly co-expressed with Aβ at early stages. Furthermore, the number of Nurr1-expressing cells significantly declines in the 5XFAD mouse in an age-dependent manner, accompanied by increased plaque deposition. Thus, our findings suggest that altered expression of Nurr1 is associated with AD progression. Using our newly developed Nurr1-selective antibody, we show that Nurr1 protein is prominently expressed in brain areas accumulating amyloid-beta (Aβ) in the transgenic mouse model of Alzheimer's disease (AD) and that Nurr1 is highly co-expressed with Aβ at early stages (upper panel). Furthermore, in the AD brain the number of Nurr1-expressing cells significantly declines in an age-dependent manner concomitant with increased Aβ accumulation (lower diagram) highlighting a possible Nurr1 involvement in AD pathology.

Alzheimer Disease - metabolism

Alzheimer Disease - pathology

Amino Acid Sequence

Amyloid beta-Peptides - metabolism

Animals

Antibody Specificity

Brain - metabolism

Cerebral Cortex - metabolism

Cerebral Cortex - pathology

Disease Models, Animal

Disease Progression

Fluorescent Antibody Technique, Direct

Hippocampus - metabolism

Hippocampus - pathology

Immunoenzyme Techniques

Mice

Mice, Transgenic

Molecular Sequence Data

Nerve Tissue Proteins - biosynthesis

Nerve Tissue Proteins - genetics

Nerve Tissue Proteins - physiology

Nuclear Receptor Subfamily 4, Group A, Member 2 - biosynthesis

Nuclear Receptor Subfamily 4, Group A, Member 2 - genetics

Nuclear Receptor Subfamily 4, Group A, Member 2 - immunology

Nuclear Receptor Subfamily 4, Group A, Member 2 - physiology

Sequence Alignment

Sequence Homology, Amino Acid

Details

Title: Subtitle: Correlation between orphan nuclear receptor Nurr1 expression and amyloid deposition in 5XFAD mice, an animal model of Alzheimer's disease
Creators: Minho Moon - Molecular Neurobiology Laboratory, McLean Hospital/Harvard Medical School, Belmont, Massachusetts, USA; Program in Neuroscience, Harvard Medical School, Belmont, Massachusetts, USA
Inhye Jeong
Chun-Hyung Kim
Jihong Kim
Paula K J Lee - University of Iowa, Neurology
Inhee Mook-Jung
Pierre Leblanc
Kwang-Soo Kim
Resource Type: Journal article
Publication Details: Journal of neurochemistry, Vol.132(2), pp.254-262
DOI: 10.1111/jnc.12935
PMID: 25156412
PMCID: PMC4301994
ISSN: 0022-3042
eISSN: 1471-4159
Grant note: R01 NS070577 / NINDS NIH HHS R21 AG046599 / NIA NIH HHS R01 NS084869 / NINDS NIH HHS NS084869 / NINDS NIH HHS NS070577 / NINDS NIH HHS
Language: English
Date published: 01/2015
Academic Unit: Neurology
Record Identifier: 9984119796002771

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