Abstract
PurposeThis study aimed at assessing gene expression profiles in hippocampus and hypothalamus of ovariectomized (OVX) rats with or without treatment with an isopropanolic extract of Cimicifuga racemosa rhizomes (iCR) in comparison to intact rats.MethodsExploration of hippocampal (Hi) and hypothalamic (Hy) tissue from Sprague Dawley rats: without OVX (NHi = NHy = 4), tissues 3 months after OVX (NHi = 4, NHy = 3), or tissues of rats after their treatment with iCR for 3 months after OVX (NHi = NHy = 2). Gene expression profiles in these tissues were investigated by RNA-microarray-analysis and subsequent verification by qPCR.Results4812 genes were differentially regulated when comparing the three groups in hippocampus and hypothalamus. iCR compensated the effects of OVX in 518 genes. This compensatory effect was most prominent in hippocampal signalling pathways, thereof genes (GAL, CALCA, HCRT, AVPR1A, PNOC, etc.) involved in thermoregulation, regulation of sleep and arousal, blood pressure regulation, metabolism, nociception, hormonal regulation, homeostasis, learning and cognition, mood regulation, neuroendocrine modulation, etc.. In the hypothalamus, iCR compensated OVX-effects at TAC3 and OPRM1 but not at KISS1. These genes are involved in the pathophysiology of hot flashes.ConclusionsOur pilot study findings support a multifaceted mode of action of iCR in menopausal complaints on a tissue-specific brain gene expression level.
Highlights
Menopause-related oestrogen decline affects the aging process of the female brain and is accompanied by a progressive decline in cognition and memory, respectively [1]
The data are shown as a cross tabulation with the top right side showing the data for the hippocampus (Hi) and the bottom left side showing the data for the hypothalamus (Hy)
The focus of this analysis was on the OVX. Group 2 (OVX) compensatory effects of isopropanolic extract of Cimicifuga racemosa rhizomes (iCR) on 518 genes
Summary
Menopause-related oestrogen decline affects the aging process of the female brain and is accompanied by a progressive decline in cognition and memory, respectively [1]. Oestrogen decline leads to a dysfunction of temperature-sensitive neurons in the hypothalamic preoptic area and other hypothalamic nuclei areas. This may explain the reduced ability to adapt to changes in ambient temperature resulting in hot flushes, the most common menopausal symptom. The hippocampus plays a major role in learning and memory. It contributes to attention, arousal, and emotional states including stress, and to. Archives of Gynecology and Obstetrics adaptive and reproductive behaviour. Hippocampal outputs are predominantly inhibitory on downstream neuroendocrine activity [2]
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