Anat Cell Biol.  2011 Jun;44(2):116-127. 10.5115/acb.2011.44.2.116.

Expression of ErbB4 in the neurons of Alzheimer's disease brain and APP/PS1 mice, a model of Alzheimer's disease

• Woo RS
• Lee JH
• Yu HN
• Song DY
• Baik TK

• KMID: 1447421
• DOI: http://doi.org/10.5115/acb.2011.44.2.116

Abstract

Neuregulin-1 (NRG1) plays important roles in the development and plasticity of the brain, and has also been reported to exhibit potent neuroprotective properties. Although ErbB4, a key NRG1 receptor, is expressed in multiple regions in the adult animal brain, little is known about its role in Alzheimer's disease (AD). AD is characterized by progressive impairment of cognition and behavioral disturbance that strongly correlate with degeneration and death of neurons in the cerebral cortex and limbic brain areas, such as the hippocampus and the amygdala. Here, we show that the ErbB4 and phospho-ErbB4 immunoreactivities were higher intensity in the neurons of the CA1-2 transitional field of AD brains as compared to age-matched controls. Also, ErbB4 expression was increased in the neurons of the cortico medial nucleus amygdala, human basal forebrain and superior frontal gyrus of AD brains. In cerebral cortex and hippocampus of amyloid precursor protein/presenilin 1 double transgenic mice, ErbB4 immunoreactivity significantly increased in comparison to age-matched wild type control. These results suggest that up-regulating of ErbB4 immunoreactivity may involve in the progression of pathology of AD.

Keyword

Alzheimer disease; ErbB4 receptor; Limbic structures; Neurodegeneration

MeSH Terms

Adult
Alzheimer Disease
Amygdala
Amyloid
Animals
Brain
Cerebral Cortex
Cognition
Hippocampus
Humans
Mice
Mice, Transgenic
Neuregulin-1
Neurons
Plastics
Prosencephalon
Amyloid
Neuregulin-1
Plastics

Figure

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  Fig. 1 Detailed analysis of pathological changes in Alzheimer's disease (AD) brains. (A) Histological analysis of semi-serial paraffin sections from AD hippocamal formation. Hematoxylin and eosin staining (H&E), Luxol fast blue/cresyl violet (LFB-CV) staining, and modified Campbell's silver staining is sequentially applied to the same sections, and the same fields at CA1. (B) Quantitative analysis of data in (A) that is neuronal loss of the hippocampal pyramidal neurons. Scale bars=100 µm. Shown are means±standard errors of the mean; n=14 for age-matched control and n=15 for AD. *P<0.05.

• 

  Fig. 2 Expression of ErbB4 and p-ErbB4 in CA1-2 of hippocampus of Alzheimer's disease (AD) brains. Paired low-power composites (A) and high-power (B) images of ErbB4 (left column) and p-ErbB4 (right column) immunoreactivity in a single hippocampal tissue section. Inset, enlarged areas. (C) Quantitative analysis of data in (B) that is ErbB4 and p-ErbB4 expressing neurons. (D) ErbB4 confocal immunoflorescence staining. Nuclei are stained with Hoechst 33342. (E) Quantitative analysis of data in (D) that are ErbB4 expressing neurons. Arrowheads, pyramidal neurons; IHC, immunohistochemistry. Scale bars=100 µm (A, B, D), 25 µm (inset [enlarged areas] of B). Shown are means±standard errors of the mean; n=14 for age-matched control and n=15 for AD. *P<0.05, **P<0.01.

• 

  Fig. 3 ErbB4 immunohistochemistry (IHC) in the corticomedial nucleus of amygdala, cholinergic neurons of the human basal forebrain (BFCN), and superior frontal gyrus of Alzheimer's disease (AD) brains. (A, D) Hematoxylin and eosin (H&E), Luxol fast blue/cresyl violet (LFB-CV) and modified Campbell's silver staining and ErbB4 immunoreactivity in the corticomedial nucleus of amygdala. (B, E) H&E, LFB-CV and modified Campbell's silver staining and ErbB4 immunoreactivity in the BFCN. (C, F) H&E, LFB-CV and modified Campbell's silver staining and ErbB4 immunoreactivity in the superior frontal gyrus. (D-F) Quantitative analysis of data in (A-C) that are ErbB4 expressing neurons. Scale bars=100 µm, 25 µm (inset [enlarged areas]). Shown are means±standard errors of the mean; n=14 for age-matched control and n=15 for AD. *P<0.05, **P<0.01.

• 

  Fig. 4 ErbB4 immunohistochemistry (IHC) in presenilin/amyloid precursor protein (PS/APP) mice. (A) Hematoxylin and eosin (H&E) and Aβ (6E10), ErbB4 immunoreactivity in the cortex and hippocampus. (B) Quantitative analysis of data in (A) that are ErbB4 expressing neurons. Scale bars=100 µm, 10 µm (inset [enlarged areas]). Shown are means±SEM; n=5 for age-matched control and n=5 for PS/APP mice. *P<0.01. (C) Immunoblot analysis of ErbB4 expression in cerebral cortex and hippocampus from PS/APP mice. AD, Alzheimer's disease; Wt, wild type; Tg, transgenic.

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