J Korean Med Sci.  2007 Oct;22(5):936-941. 10.3346/jkms.2007.22.5.936.

Reactive Astrocytes Expressing Intense Estrogen Receptor-alpha Immunoreactivities Have Much Elongated Cytoplasmic Processes: An Autopsy Case of Human Cerebellar Tissue with Multiple Genitourinary and Gastrointestinal Anomalies

• Kim EJ
• Oh CS
• Kim J
• Kim WH
• Chung YH
• Shin DH

• KMID: 1713309
• DOI: http://doi.org/10.3346/jkms.2007.22.5.936

Abstract

We performed an immunohistochemical study on the estrogen receptor alpha (ER-alpha) distribution in the cerebellum of a human neonate with multiple congenital anomalies, that had been acquired during autopsy. Although the exact pathology in the brain was not clearly elucidated in this study, an unidentified stressful condition might have induced the astrocytes into reactive states. In this immunohistochemical study on the neonatal cerebellum with multiple congenital anomalies, intense ER-alpha immunoreactivities (IRs) were localized mainly within the white matter even though ER-alpha IRs were known to be mainly localized in neurons. Double immunohistochemical staining showed that ER-alpha IR cells were reactive astrocytes, but not neurons. Interestingly, there were differences in the process length among the reactive astrocytes showing ER-alpha IRs. Our quantitative data confirmed that among the glial fibrillary acidic protein (GFAP)-expressing reactive astrocytes, the cells exhibiting intense ER-alpha IRs have much longer cytoplasmic processes and relatively weaker GFAP IRs. Taken together, the elongated processes of reactive astrocytes might be due to decreased expression of GFAP, which might be induced by elevated expression of ER-alpha even though the elucidation of the exact mechanism needs further studies.

Keyword

Estrogen Receptor Alpha; Infant, Newborn; Brain; Immunohistochemistry; Cerebellum; Astrocytes; Glial Fibrillary Acidic Protein

MeSH Terms

Abnormalities, Multiple/*pathology
Astrocytes/*metabolism
Autopsy
Brain/pathology
Cerebellum/*metabolism
Cytoplasm/metabolism
Estrogen Receptor alpha/*metabolism
Female
Gastrointestinal Diseases/congenital/*pathology
*Gene Expression Regulation
Glial Fibrillary Acidic Protein/metabolism
Humans
Immunohistochemistry/methods
Infant, Newborn
Urogenital Abnormalities/*pathology

Figure

• 

  Fig. 1 (A) and (B) Estrogen receptor alpha (ER-α) immunoreactivities (IRs) in the cerebellum of a human neonate with multiple congenital anomalies. (B) is the magnified image of (A). W, white matter; Gr, granular layer; M, molecular layers. Yellow arrows indicate ER-α IR cells exhibiting extended processes around all directions. (C) Double immunohistochemical study using antineurofilament and anti-ER-α antibodies in the cerebellum of the human neonate with multiple congenital anomalies. Neurofilament IRs (green, indicated by white arrows); ER-α IRs (red); Nuclei stained with DAPI (blue). Scale Bars, 40 µm.

• 

  Fig. 2 Double immunohistochemical study on the cell type of estrogen receptor-alpha (ER-α) immunoreactivity (IR) cells in the cerebellum of a human neonate with multiple congenital anomalies. (A) for anti-glial fibrillary acidic protein (GFAP); (B) for anti-ER-α antibodies; (C) is the merged image of (A) and (B). Intensely ER-α IR astrocytes with longer processes were encircled by white dotted line. Astrocytes with weaker ER-α IRs were encircled by a yellow dotted line. Scale bars, 20 µm.

• 

  Fig. 3 Comparison of reactive astrocytes with short (A, B) and long processes (C, D). (A) and (C) for glial fibrillary acidic protein (GFAP) immunoreactivities (IRs). (B) and (D) for estrogen receptor alpha (ER-α) IRs. Scale bars, 20 µm.

• 

  Fig. 4 Quantitative analysis on the relationship between the process length and the intensities of ER-α or GFAP IRs of reactive astrocytes. A p value of less than 0.01 was deemed statistically significant.

• 

  Fig. 5 Double immunohistochemical study using (A) OX-42 and (B) estrogen receptor alpha (ER-α) antibodies. (C) is the merged image of (A) and (B). (D) is merged image of (C) and DAPI stained image. ER-α immunoreactivity (IR) cells were not microglia because OX-42 IR microglia (indicated by yellow arrows) did not exhibit ER-α IRs. Scale Bars, 20 µm.

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