Aromatase Expression in the Hippocampus of AD Patients and 5xFAD Mice.
Numerous studies show that 17β-estradiol (E2) protects against Alzheimer's disease (AD) induced neurodegeneration. The E2-synthesizing enzyme aromatase is expressed in healthy hippocampi, but although the hippocampus is severely affected in AD, little is known about the expression of hippocampal aromatase in AD. To better understand the role of hippocampal aromatase in AD, we studied its expression in postmortem material from patients with AD and in a mouse model for AD (5xFAD mice). In human hippocampi, aromatase-immunoreactivity was observed in the vast majority of principal neurons and signal quantification revealed higher expression of aromatase protein in AD patients compared to age- and sex-matched controls. The tissue-specific first exons of aromatase I.f, PII, I.3, and I.6 were detected in hippocampi of controls and AD patients by RT-PCR. In contrast, 3-month-old, female 5xFAD mice showed lower expression of aromatase mRNA and protein (measured by qRT-PCR and semiquantitative immunohistochemistry) than WT controls; no such differences were observed in male mice. Our findings stress the importance of hippocampal aromatase expression in neurodegenerative diseases.
Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Janine
J
Prange-Kiel
Institute of Neuroanatomy, University Medical Center Hamburg Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Danuta A
DA
Dudzinski
Institute of Neuroanatomy, University Medical Center Hamburg Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Felicitas
F
Pröls
Institute of Neuropathology, University Medical Center Hamburg Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Markus
M
Glatzel
Institute of Neuropathology, University Medical Center Hamburg Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Jakob
J
Matschke
Institute of Neuroanatomy, University Medical Center Hamburg Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Gabriele M
GM
Rune
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged
D001141:Aromatase; C561410:CYP19A1 protein, human