ABSTRACT
Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mito-chondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mito-chondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upre-gulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.
ABSTRACT
Physical and psychological stresses inhibit or harm reproductive endocrine especially female one at many levels of hypothalamo-pituitary-gonadal (HPG) axis, and result in subhealth conditions or clinic diseases in reproductive endocrine. The hypothalamic corticotropin-releasing factor (CRF) and adrenal glucocorticoids (GCS) overreleases and other neuroendocrine alterations induced by stress are implicated in the mechanisms responsible for the disturbance of reproductive endocrine. The declines in activities of synzyms for reproductive hormones cause sexual hormones reduces and disfunction in reproductive endocrine system.
ABSTRACT
AIM : To observe the effect of stress and ovariectomy on behavior activity in mice and the prevention and therapy of the TCM complexⅠcomposed of spine date seed and common anemarrhena rhizome. METHODS : The effect of stress and ovariectomy were investigated on bedtime, survival time under hypoxia, climbing time on the string and number of times of the activity in mice, and the prevention and therapy of TCM the complexⅠwere observed. RESULTS : The effect of stress, ovariectomy, stress and ovariectomy were different on bedtime, survival time under hypoxia and climbing time on the string and the number of times of the activity in mice. The effect of stress and ovariectomy on previous parameters was stronger than that of stress or ovariectomy lonely in mice. The stress and ovariectomy resulted in sleep impairment, the decreasing of the survival time under hypoxia and climbing time on the string, and the increasing of the number of times of the activity in mice. CONCLUSION : The TCM complex I can alleviate the high sensitivity to the environment in mice with ovariectomy and stress, which is similar to the mechanism of human climacteric syndrome.
ABSTRACT
Objective To observe the effects of repeated immobilization on rats ovarian function and to observe the changes of ovarian function in menopause animals.Methods Daily vaginal smears were permfored to follow the estrous cycle in adult female rats.The animals with regular cycle were exposed to the scheduled daily repeated immobilization for 15-day,which included 5 stress episodes with each episode consisting of three immobilizations (one time per day). The duration of immobilization was progressively increased with the subsequent episode. Serum levels of estradiol (E2) and progesterone (P) were measured throughout the estrous cycle before and after the stress.Results The repeated stress resulted in the disruption of the estrous cycle characterized by longer phase of diestrus or by fewer epithelium from vagina in proestrus and estrus.In the stressed rats, a significant decrease of serum E2 and an increase of P were shown throughout the cycle compared to that before stress;the normal secretion cycle was interrupted or even disappeared; changes of serum P level in some rats were similar to the menopause animals.Conclusion Repeated immobilization can cause the disruption or degeneration of ovarian function,indicating that rats with stress-induced ovarian dysfunction is an appropriate animal model for testing protective effects of agents against aging and for the diseases related to ovarian dysfunction.
ABSTRACT
Objective To observe the effects of acute stress on reproductive- endocrine function in female adult rats. Methods Acute immobilization stress was used to challenge the female adult rats and then the serum levels of progesterone (P), estradiol (E2) and corticosterone were measured 2 h after the stress.Results Acute stress significantly reduced E2 levels in each period of sexual cycle and increased the levels of P and corticosterone in the stressed rats.In addition, the ratio of estradiol and progesterone was disordered in stressed rats.Conclusion Acute stress can cause the disorder of estradiol and progesterone.Since stress is a major factor contributing to reproductive- endocrine disorder, this model will be useful for the research and development of drugs for reproductive- endocrine disorder.