Anat Cell Biol.  2010 Dec;43(4):332-339. 10.5115/acb.2010.43.4.332.

Expression of ErbB4 in the apoptotic neurons of Alzheimer's disease brain

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

• KMID: 1455348
• DOI: http://doi.org/10.5115/acb.2010.43.4.332

Abstract

Neuregulin-1 (NRG1) signaling participates in the synaptic plasticity, maintenance or regulation of adult brain. Although ErbB4, a key NRG1 receptor, is expressed in multiple regions in the adult animal brain, little is known about its localization in Alzheimer's disease (AD) brains. We previously reported that ErbB4 immunoreactivity showed regional difference in the hippocampus of age-matched control. In the present paper, immunohistochemical characterization of the distribution of ErbB4 receptor in the hippocampus relative to pathology staging were performed in age-matched control (Braak stage 0, n=6) and AD (Braak stage I/V, n=10). Here, we found that ErbB4 immunoreactivity was significantly increased in apoptotic hippocampal pyramidal neurons in the brains of AD patients, compared to those of age-matched control subjects. In AD brains, ErbB4 immunoreactivity was demonstrated to colocalize with the apoptotic signal Bax in apoptotic hippocampal pyramidal neurons. These results suggest that up-regulation of ErbB4 immunoreactivity in apoptotic neuron may involve in the progression of pathology of AD.

Keyword

Alzheimer's disease; ErbB4 receptor; Bax; Apoptosis; Neurodegeneration

MeSH Terms

Adult
Alzheimer Disease
Animals
Apoptosis
Brain
Hippocampus
Humans
Neuregulin-1
Neurons
Plastics
Up-Regulation
Neuregulin-1
Plastics

Figure

• 

  Fig. 1 Detailed analysis of pathological changes in AD brains. Light micrographs of the CA1-2 transitional field of hippocampus. H&E, LFB-CV and modified Campbell's silver stain were sequentially applied to the semi-serial sections n=6 for age-matched control, n=10 for advanced AD. Scale bar = 100 µm.

• 

  Fig. 2 Apoptosis within the hippocampus of AD brains. TUNEL staining in the CA1-2 transitional field of age-matched control and AD. n=6 for age-matched control and n=10 for AD. Scale bars = 100 µm.

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  Fig. 3 Double immuno-labeling studies on ErbB4 and Bax in the hippocampal pyramidal neurons of the CA1-2 transitional field of AD brains. Double immunohistochemistry on Bax (NovaRED: Red) and ErbB4 (Nickel-DAB: grey). (B) Quantitative analysis of data in (A). Shown are means±SEM. *P<0.05. Scale bars, 100 µm and 10 µm in inset (enlarged areas) of (A).

• 

  Fig. 4 ErbB4 and Bax confocal double immunofluorescence staining showing that colocalization of ErbB4 with Bax in the hippocampus of AD brains. In the age-matched control, ErbB4 (FITC) and Bax (Rhodamine) are not colocalized in the hippocampal pyramidal neurons (arrowheads). In advanced AD, ErbB4 and Bax are colocalized in the hippocampal pyramidal neurons (arrows). Nuclei are stained with Hoechst 33342. Scale bar: 25 µm. Arrows, pyramidal neurons. (B) Quantitative analysis of data in (A). Shown are means ± SEM. *P<0.05.

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