Estrogen therapy increases BDNF expression and improves post-stroke depression in ovariectomy-treated rats

Abstract

Abstract. The present study investigated the effect of exogenous estrogen on post-stroke depression. Rats were exposed to chronic mild stress following middle cerebral artery occlusion. The occurrence of post-stroke depression was evaluated according to the changes in preference for sucrose and performance in a forced swimming test. Estrogen therapy significantly improved these neurological symptoms, indicating that estrogen is effective in treating post-stroke depression. Increased brain-derived neurotrophic factor (BDNF) expression was reported in the hippocampus of rats that had been treated with estrogen for two weeks, suggesting that BDNF expression may be an important contributor to the improvement of post-stroke depression that is observed following estrogen therapy. IntroductionDepression is a common complication of stroke, occurring in ~33% of patients (1,2); the clinical symptoms of this include feelings of guilt, low self-esteem, reduction in food intake, sleep disorders and fatigue. There are between 1.6-2.0 million new stroke patients in China every year and post-stroke depression (PSD) is closely associated with the increased risk of mortality following a stroke (3). PSD negatively impacts upon subsequent rehabilitation; in a previous study by Sinyor et al, PSD patients demonstrated greater functional impairment than patients without depression, also scoring lower on behavioral action and functional status (4). The severity of depression is closely associated with health-associated quality of life and functional recovery in stroke survivors (5). PSD patients demonstrate a negative mood during rehabilitation and achieve poorer outcomes during functional recovery therapy. These patients also have greater difficulty in restoring social activities (6). Several studies have described a higher mortality rate in stroke patients with depression (7), and certain studies have reported that PSD patients using antidepressant drugs demonstrate improved ability to function than those without antidepressant therapy. The treatment of depression has been demonstrated to aid functional recovery (8), meaning that the early diagnosis and effective treatment of PSD are crucial to recovery from a stroke.Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which regulates neurogenesis (9), apoptosis (10), the expression level of monoamine transmitters (11), and the function and plasticity of synapses (12). Neurotrophins may be key in the development of depression (13); BDNF, for instance, can activate intracellular mitogen-activated protein kinase/extracellular signal-regulated kinase cascade signaling pathways (14), affecting synaptic plasticity (12) and alleviating the symptoms of depression (15), and BDNF may thus be important in the maintenance of emotional stability. Deletion of the BDNF receptor induces a reduction in neurogenesis and increases anxious behavior (16). Additionally, BDNF expression is associated with 5-hydroxytryptamine receptor expression in the brain, particularly the hi...

Effects of Vitamin D3 in Long-Term Ovariectomized Rats Subjected to Chronic Unpredictable Mild Stress: BDNF, NT-3, and NT-4 Implications

“…The menopausal period—a very specific state for women—is produced by the decreased secretion of the female gonadal hormones by the ovaries [1,2,3]. Numerous data of preclinical and clinical studies have shown that estrogen deficiency during menopause increases the susceptibility to mood disturbances, including depression [4,5,6,7]. On the other hand, the menopausal state in ovariectomized (OVX) female rodents and menopausal women is also characterized by vitamin D (VD) deficiency or insufficiency [8,9,10,11].…”

Low Intensity Pulsed Ultrasound Prevents Recurrent Ischemic Stroke in a Cerebral Ischemia/Reperfusion Injury Mouse Model via Brain-derived Neurotrophic Factor Induction

“…BDNF is known to be a neurotrophic protective factor, involved in the regulation of several critical neuronal functions and neuroplasticity in patients who suffer nervous system diseases such as Parkinson’s disease, Alzheimer’s disease, and stroke [35,36,37]. Several empirical studies have indicated the benefits of the increased expression of BDNF or receptor in different stages of stroke such as acute ischemic stroke, the rehabilitation process, and recurrence [37,38,39,40]. The expression of BDNF has been demonstrated to have benefits on stroke recovery through several mechanisms and proposed actions including the increase in brain repair [7], the acceleration of neurogenesis [41], and the promotion of angiogenesis [42].…”

Identification and bioinformatics analysis of overlapping differentially expressed genes in depression, papillary thyroid cancer and uterine fibroids

“…Furthermore, interconnections between the hypothalamic-pituitary-ovarian (HPO) and HPT axes have been reported; notably hypothyroidism is closely associated with hyperprolactinemia, as well as menstrual problems, including oligomenorrhea, amenorrhoea and polymenorrhea ( 50 ). Therefore, an imbalance of hormones acting at the HPT and HPO axes may have adverse effects on mental, thyroid and/or uterine health ( 51 ).…”