Volume 15, Number 59 (summer 2008)                   RJMS 2008, 15(59): 181-190 | Back to browse issues page

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Nobakht, M, Shafiee , M, Tabatabaee, P, Rastegar, T. Assessment of Tamoxifen Effects on Nitric Oxide Synthase (NOS) in Rat's Developing Hippocampus. RJMS. 2008; 15 (59) :181-190
URL: http://rjms.iums.ac.ir/article-1-1023-en.html

Associate Professor
Abstract:   (5457 Views)

Background & Aim:

treatment, as an estrogen antagonist, induces cell death in rat's developing hippocampus. Estrogen has a

variety of physiological effects on the nervous system, including regulation of cognitive functions, learning,

aging, angiogenesis, neurogenesis, and neuroprotective effects. In the present study, we demonstrated the

effects of TAM as an estrogen antagonist on nitric oxide synthase activity in rat's developing hippocampal

pyramidal neurons.

Maternal steroids modulate various functions in the developing brain. Tamoxifen (TAM)

Material and Method:

animals were divided randomly into control, experimental and sham groups. Each group contained full term

embryo (E

group received a total of four doses of TAM,i.e. 250 mg/kg TAM in propylene glycole was injected

intraperitoneally twice a day for two days. Their hippocampus was removed 6 hours after the last injection.

Animals at the same gestational age were used as shams and controls. The latter received only propylene

glycole. The hippocampus was dissected out and stored in fixative and sucrose. Cryostat sections were thawmounted

on gelatin slides. The sections were incubated for NADPH-diaphorase histochemistry by light

microscope. Independent sample t-test and SPSS version 11.0 were used to analyze the data.

The present experimental study was conducted on twelve groups of adult rats. The22), one-day neonate (P1), one-week neonate (P7), and three -week neonate (P21). The experimental


thickness increases so that the most thickness is seen in the third week after birth. Considering the short halftime

of TAM, it was observed that tamoxifen had its greatest effects on E

estrogen receptors. In the group that didn't receive tamoxifen, due to the presence of estrogen NADPHdiaphorase

activity, which indicates NOS activity level, strengthened. On the other hand, the animals which

received tamoxifen in the early stage showed a decrease in NADPH-diaphorase activity owing to estrogen

receptor blockade. Furthermore, the number of neural cells in CA1 hippocampal region showed a decrease in

proportion to the reduction in NOS activity level in this region. The decreased number of neural cells and NOS

activity, which was seen in E

We found that in the early stage of development cellular density decreases and gradually cellular22, P1 and P7 groups and blockaded22, P1 , P7 groups, seems to be due to the short half-time of tamoxifen.


oxide-mediated growth and development of hippocampal pyramidal cells.

These findings indicate that estrogen and selective estrogen modulators can influence nitric
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Type of Study: Research | Subject: Pharmacology

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