17beta-estradiol attenuates hippocampal neuronal loss and cognitive dysfunction induced by chronic restraint stress in ovariectomized rats.

Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
Neuroscience (Impact Factor: 3.33). 05/2007; 146(1):60-8. DOI: 10.1016/j.neuroscience.2007.01.017
Source: PubMed

ABSTRACT Several lines of evidence suggest that hormonal changes after menopause may play an important role in the incidence of cognitive dysfunction, and also in the development of Alzheimer's disease. In this study, we investigated the effect of estrogen on cognitive function in rats under different stress environment. Female rats were divided into four groups: two groups were ovariectomized (OVX) and two were sham-operated. One group each of OVX and sham rats was kept in a normal environment, and the other groups were assigned to a daily restraint stress (6 h/day) for 21 days from 2 months after the operation. Following the stress period, subjects were tested for performance in novel object recognition test and then used for morphological and neurochemical analyses. The OVX plus stress (OVX/stress) group showed a significant impairment of recognition of novel objects, compared with the other groups. The OVX/stress group also showed a marked decrease in the number of pyramidal cells of the CA3 region and levels of brain-derived neurotrophic factor mRNA in the hippocampus. We further examined the effect of estrogen against cognitive dysfunction and hippocampal changes of OVX/stress rats. Vehicle or 17beta-estradiol (E2) at 20 microg/day was s.c. administered to OVX/stress rats from 2 days before the stress period to the end of behavioral analysis through an implantable osmotic pump. Chronic E2 treatment decreased stress response and improved the cognitive and morphological impairments relative to vehicle group. These data have important implications for cognition enhancing effect of estrogen treatment in postmenopausal women.

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    ABSTRACT: This study evaluated the effects of Tualang honey on the medial prefrontal cortex (mPFC) morphology and the brain cholinergic system in stressed ovariectomised (OVX) rats. Sixty female Sprague-Dawley rats were divided into six groups: (i) unstressed sham-operated control rats, (ii) stressed sham-operated control rats, (iii) nonnstressed OVX rats, (iv) stressed OVX rats, (v) stressed OVX rats treated with 17 β-oestradiol (20 µg daily, sc) and (vi) stressed OVX rats treated with Tualang honey (0.2 g/kg body weight, orally). After social instability stress, the rats were sacrificed, and the right and left brain hemispheres were isolated for histological studies and estimation of acetylcoline (ACh) and acetylcholinesterase (AChE) concentrations. Stressed OVX rats showed reduced concentrations of ACh and increased AChE in the brain homogenates compared with nonstressed sham-operated controls and the effects were reversed after treatment with either 17 β-oestradiol or Tualang honey. The arrangement and number of Nissl positive cells in the mPFC neurons were significantly improved in stressed OVX rats treated with either 17 β-oestradiol or Tualang honey compared to untreated stressed OVX rats. In conclusion, treatment with either 17 β-oestradiol or Tualang honey significantly improved the morphology of mPFC, increased ACh and reduced AChE concentrations in stressed ovariectomised rats. Industrial relevance. Although the currently available hormone replacement therapy is valuable in the management of postmenopausal symptoms, it needs close monitoring of the side effects. Because of this, there is a need for a safe alternative treatment to alleviate postmenopausal symptoms. In view of the fact that most natural products have little or no known side effects, coupled with previous studies reporting neuroprotective benefits of Tualang honey, it is deemed a suitable alternative therapy to alleviate some of the neurological symptoms in postmenopausal women.

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