Elsevier

Biological Psychiatry

Volume 58, Issue 10, 15 November 2005, Pages 812-824
Biological Psychiatry

Original article
Alteration in Estrogen Receptor α mRNA Levels in Frontal Cortex and Hippocampus of Patients with Major Mental Illness

https://doi.org/10.1016/j.biopsych.2005.04.047Get rights and content

Background

Gender differences have been described in major mental illnesses (MMI). The dorsolateral prefrontal cortex (DLPFC) and hippocampus are estrogen-sensitive brain regions structurally and functionally altered in patients with MMI. We hypothesized that gender-specific alterations in DLPFC and hippocampus estrogen receptor α (ERα) mRNA levels may exist in MMI patients.

Methods

We used Northern blot analysis to survey the expression of ERα mRNA transcripts in brain and body, detected by our human ERα riboprobe and in situ hybridization, to examine the expression pattern and quantify ERα mRNA levels in DLPFC and anterior hippocampus of patients with major depressive disorder (MDD), schizophrenia, and bipolar disorder compared with normal control subjects.

Results

Northern blotting revealed brain-region-specific differences in expression levels of a 5 kb ERα mRNA transcript. By in situ hybridization, ERα mRNA was detected in all layers of DLPFC and all hippocampal subfields in all subjects. We detected greater DLPFC ERα mRNA expression in male compared with female MDD subjects and reduced ERα mRNA levels in the dentate gyrus of schizophrenics compared with control subjects.

Conclusions

Our results suggest that alterations in ERα mRNA levels exist in distinct telencephalic regions in male and female MDD patients, and in both genders in schizophrenia.

Section snippets

Tissue

Separate sets of frozen 14-μm-thick coronal sections from DLPFC (middle frontal gyrus containing Brodmann’s area 46) and the anterior hippocampus at the level of the genu were obtained from the Stanley Foundation Neuropathology Consortium. Sections were acquired from 60 individuals divided into 4 groups, 15 subjects each of normal control subjects and patients with schizophrenia, bipolar disorder, and major depression without psychotic features. Tissue processing, clinical information, and

Northern Blot

In the reproductive and nonreproductive tissue blots, our ERα riboprobe recognized two major transcripts greater than 4.4 kb, one of approximately 6.5 kb, and another of approximately 5 kb, as well as several smaller transcripts (Figure 1, left and right blots). We detected a 6.5-kb transcript in uterus, cervix, and skeletal muscle (Figure 1), consistent with previous reports (Brandenberger et al 1998; Chiang et al 2000). A 5-kb transcript was also detected in uterus, cervix, and skeletal

Discussion

By Northern blot, we detected two large ERα mRNA transcripts (approximately 6.5 and 5 kb, respectively), only one of which (5 kb) was detectable in the brain regions we examined. The high ERα mRNA expression we detected in deep layers of the cortex is in agreement with results reported from human temporal cortex (Osterlund et al 2000a, Osterlund et al 2000b, Osterlund et al 2000c). In addition, our study presents the first quantitative description of ERα mRNA distribution in the DLPFC and

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