Gonadal Hormones And Frontocortical Expression Of Vascular Endothelial Growth Factor In Male Stroke- Prone, Spontaneously Hypertensive Rats, A Model For Attention-Deficit/Hyperactivity Disorder

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Dr.. Chishimba Nathan Mowa, Associate Professor (Creator)
Appalachian State University (ASU )
Web Site: https://library.appstate.edu/

Abstract: Attention-deficit/hyperactivity disorder (AD/HD) is a common pediatric behavioral disorder associated, in part, with male preponderance and reduced regional cerebral blood flow (rCBF). However, mechanism(s) underlying male preponderance and reduced rCBF in AD/HD are unclear. The present study profiles the expression of angiogenic and hormonal factors likely to underlie these symptoms using a recently characterized AD/HD animal model, juvenile male stroke-prone spontaneously hypertensive rats (SHRSP). Because vascular endothelial growth factor (VEGF) signaling cascade and gonadal steroids are key regulators of angiogenesis and gender based behavior, respectively, we profiled their patterns of expression in the frontal cortex of SHRSP to elucidate their roles in the genesis of AD/HD male preponderance and rCBF. Interestingly, levels of VEGF, VEGF receptors (KDR, Flt-1), endothelial nitric oxide synthase, phosphorylated Akt (pAkt), estrogen receptor-B, aromatase, and capillary density in sham-operated SHRSP were remarkably down-regulated, whereas androgen receptor levels were up-regulated, compared with age-matched genetic control, Wistar-Kyoto rats. Castration, estrogen, and androgen receptor antagonist (flutamide) counteracted these effects. Dihydrotestosterone, but not testosterone, reversed the beneficiary effects of castration. Estrogen receptor-B levels remained unchanged in all groups examined. We postulate that changes in androgen metabolism that tend to up-regulate local dihydrotestosterone concentration and diminish estrogen synthesis, in the frontal cortex of juvenile male SHRSP, may lower levels and/or activity of VEGF and its signaling cascade and, subsequently, reduce rCBF. These findings could, in part, help explain the pathogenesis of reduced rCBF and male preponderance in AD/HD.

Additional Information

Subrina Jesmin, Hiroko Togashi, Ichiro Sakuma, Chishimba N. Mowa, Ken-Ichi Ueno, Taku Yamaguchi, Mitsuhiro Yoshioka, And Akira Kitabatake (2004) "Gonadal Hormones and Frontocortical Expression of Vascular Endothelial Growth Factor in Male Stroke-Prone, Spontaneously Hypertensive Rats, a Model or Attention-Deficit/Hyperactivity Disorder" Endocrinology 145(9): 4330-4343 Version of Record Available At www.academic.oup.com [DOI: 10.1210/en.2004-0487]
Language: English
Date: 2004
Gonadal hormones, ADHD, stroke prone, VEGF

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