scholarly journals Estradiol Replacement Alters Expression of Genes Related to Neurotransmission and Immune Surveillance in the Frontal Cortex of Middle-Aged, Ovariectomized Rats

Endocrinology ◽  
2010 ◽  
Vol 151 (8) ◽  
pp. 3847-3862 ◽  
Author(s):  
Miklós Sárvári ◽  
Imre Kalló ◽  
Erik Hrabovszky ◽  
Norbert Solymosi ◽  
Kinga Tóth ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Frontal Cortex ◽  
Expression Profiling ◽  
Hormone Replacement ◽  
Immune Surveillance ◽  
Ovariectomized Rats ◽  
Middle Aged ◽  
Wide Range ◽  
Frontal Cerebral Cortex ◽  
Genomic Effects

Estradiol (E2) modulates a wide range of functions of the frontal cerebral cortex. From the onset of menopause, declining levels of E2 can cause cognitive disturbances and changes in behavior that can be counterbalanced by hormone replacement. To study the effect of E2 replacement on the cortical transcriptome in a rodent model with low serum E2 level, we treated middle-aged, ovariectomized rats with E2 or vehicle using osmotic minipumps for 4 wk. Six animals for each group were selected, and samples of their frontal cortex were subjected to expression profiling using oligonucleotide microarrays. The explored E2-regulated genes were related to neurotransmission (Adora2a, Cartpt, Drd1a, Drd2, Gjb2, Nts, and Tac1), immunity (C3, C4b, Cd74, Fcgr2b, Mpeg1, and RT1-Aw2), signal transduction (Igf2, Igfbp2, Igfbp6, Rgs9, and Sncg), transport (Abca1, Hba-a2, Slc13a3, and Slc22a8), extracellular matrix (Col1a2, Col3a1, Fmod, and Lum), and transcription (Irf7 and Nupr1). Seventy-four percent of the transcriptional changes identified by microarray were confirmed by quantitative real-time PCR. The genes identified by expression profiling indicated that chronic E2 replacement significantly altered the transcriptome of the frontal cortex. The genomic effects of E2 influenced dopaminergic and peptidergic neurotransmission, immune surveillance, adenosine and insulin-like growth factor signaling and transport processes, among other functions. Identification of these novel E2-regulated mechanisms highlights the wide range of genomic responses of the aging female frontal cerebral cortex subjected to hormone replacement. Some of the genomic effects identified in this study may underlie the beneficial effects of E2 on cognition, behavior, and neuroprotection.

scholarly journals Histomorphometric and immunohistochemical evaluation of the frontal cerebral cortex in diabetic rats after treatment with melatonin

2020 ◽  
Vol 40 (12) ◽  
pp. 1077-1087
Author(s):  
Marina G.P. Baptista ◽  
Cintia G.M. Ferreira ◽  
Yuri M.L. Albuquerque ◽  
Carolline G. D’assunção ◽  
Rebeca C. Alves ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Frontal Cortex ◽  
Intraperitoneal Administration ◽  
Diabetic Rats ◽  
Hypoglycemic Agents ◽  
Albino Rats ◽  
Tnf Α ◽  
Frontal Cerebral Cortex ◽  
The Impact ◽  
The Brain

ABSTRACT: The central nervous system is vulnerable to complications caused by diabetes. These complications lead to increased oxidative stress in the brain, resulting in damage to the cerebral cortex, among other regions. Insulin and hypoglycemic agents are still the most widely used treatments. However, current research with an experimental model of diabetes suggests the use of antioxidants, such as melatonin. Thus, we tested the hypothesis that exogenous melatonin may decrease or prevent the effects of diabetes in the frontal cortex of the rat brain. Fifty albino rats were allocated into five groups: GC = rats without diabetes induction, GD = diabetic rats induced by streptozotocin, GDM = streptozotocin-induced and melatonin-treated diabetic rats, GDI = diabetic rats induced by streptozotocin and treated with insulin, GDMI = diabetic rats induced by streptozotocin and treated with melatonin and insulin simultaneously. Diabetes was induced by intraperitoneal administration of streptozotocin (60mg/kg). Insulin (5U/day) was administered subcutaneously and melatonin (10mg/kg) by drinking water; both treatments last days after. We analyzed animals’ weight, the cytokines IL-6 and TNF-α, apoptosis, glycogen, and did morphometry and histopathology of the frontal cortex were analyzed. The results showed that the cerebral cortex of the diabetic animals presented axonal degeneration, reduced number of neurons in the cortex, reduced glycogen, increased IL-6 and TNF-α expression, high apoptotic index, and reduced animal weight and the brain. Treatment with melatonin associated or not with insulin prevented such effects. Thus, we conclude that melatonin associated with insulin may be an alternative for avoiding the impact of diabetes in the brain’s frontal cortex.

scholarly journals Gene Expression Profiling Identifies Key Estradiol Targets in the Frontal Cortex of the Rat

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1161-1176 ◽  
Author(s):  
Miklós Sárvári ◽  
Erik Hrabovszky ◽  
Imre Kalló ◽  
Orsolya Galamb ◽  
Norbert Solymosi ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Frontal Cortex ◽  
Psychiatric Disorders ◽  
Signaling Pathway ◽  
Gonadal Hormones ◽  
Ovariectomized Rats ◽  
Normal Operation ◽  
Regulation Of Transcription ◽  
Calcium Signaling Pathway ◽  
Wide Range

Estradiol modulates a wide range of neural functions in the frontal cerebral cortex where subsets of neurons express estrogen receptor-α and -β. Through these receptors, estradiol contributes to the maintenance of normal operation of the frontal cortex. During the decline of gonadal hormones, the frequency of neurological and psychiatric disorders increases. To shed light on the etiology of disorders related to declining levels of estrogens, we studied the genomic responses to estradiol. Ovariectomized rats were treated with a sc injection of estradiol. Twenty-four hours later, samples from the frontal cortices were dissected, and their mRNA content was analyzed. One hundred thirty-six estradiol-regulated transcripts were identified on Rat 230 2.0 Expression Array. Of the 136 estrogen-regulated genes, 26 and 36 genes encoded proteins involved in the regulation of transcription and signal transduction, respectively. Thirteen genes were related to the calcium signaling pathway. They comprised five genes coding for neurotransmitter receptors. Transcription of three neuropeptides, including cocaine- and amphetamine-regulated transcript, were up-regulated. Fifty-two genes were selected for validation, and 12 transcriptional changes were confirmed. These results provided evidence that estradiol evokes broad transcriptional response in the cortex. Modulation of key components of the calcium signaling pathway, dopaminergic, serotonergic, and glutamatergic neurotransmission, may explain the influence of estrogens on cognitive function and behavior. Up-regulation of cocaine- and amphetamine-regulated transcript contributes to the neuroprotective effects of estradiol. Identification of estradiol-regulated genes in the frontal cortex helps to understand the pathomechanism of neurological and psychiatric disorders associated with altered levels of estrogens.

Oligodendrocytes in Developing Hameter Cerebral Cortex

1976 ◽  
Vol 34 ◽  
pp. 126-127
Author(s):  
MB. Tank Buschmann
Keyword(s):  
Cerebral Cortex ◽  
Optic Nerve ◽  
Frontal Cortex ◽  
Osmium Tetroxide ◽  
Sodium Cacodylate Buffer ◽  
Sodium Cacodylate ◽  
Tissue Samples ◽  
Cacodylate Buffer ◽  
Layer V ◽  
Adult Hamster

Development of oligodendrocytes in rat corpus callosum was described as a sequential change in cytoplasmic density which progressed from light to medium to dark (1). In rat optic nerve, changes in cytoplasmic density were not observed, but significant changes in morphology occurred just prior to and during myelination (2). In our study, the ultrastructural development of oligodendrocytes was studied in newborn, 5-, 10-, 15-, 20-day and adult frontal cortex of the golden hamster (Mesocricetus auratus).Young and adult hamster brains were perfused with paraformaldehyde-glutaraldehyde in sodium cacodylate buffer at pH 7.3 according to the method of Peters (3). Tissue samples of layer V of the frontal cortex were post-fixed in 2% osmium tetroxide, dehydrated in acetone and embedded in Epon-Araldite resin.

scholarly journals Less Carcinogenic Chlorinated Estrogens Applicable to Hormone Replacement Therapy

2021 ◽  
Vol 22 (13) ◽  
pp. 7222
Author(s):  
Yoshinori Okamoto ◽  
Hideto Jinno ◽  
Shinji Itoh ◽  
Shinya Shibutani
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Metabolic Activation ◽  
Ovariectomized Rats ◽  
Estrogenic Potential ◽  
Carcinogenic Potential ◽  
Induced Tumors ◽  
Carcinogenic Effects ◽  
17Β Estradiol

Human estrogens prescribed for hormone replacement therapy (HRT) are known to be potent carcinogens. To find safer estrogens, several chlorinated estrogens were synthesized and their carcinogenic potential were determined. A pellet containing either 2-chloro-17β-estradiol (2-ClE2) or 4-chloro-17β-estradiol (4-ClE2) was implanted subcutaneously for 52 weeks into August Copenhagen Irish (ACI) rats, a preferred animal model for human breast cancer. 17β-Estradiol (E2) frequently induced mammary tumors while both 2-ClE2 and 4-ClE2 did not. Their 17α-ethinyl forms, thought to be orally active estrogens, were also synthesized. Neither 2-chloro-17α-ethinylestradiol (2-ClEE2) nor 4-chloro-17α-ethinylestradiol (4-ClEE2) induced tumors. The less carcinogenic effects were supported by histological examination of mammary glands of ACI rats treated with the chlorinated estrogens. A chlorine atom positioned at the 2- or 4-position of E2 may prevent the metabolic activation, resulting in reducing the carcinogenicity. 2-ClE2 and 4-ClE2 administered subcutaneously and 2-ClEE2 and 4-ClEE2 given orally to ovariectomized rats all showed uterotrophic potency, albeit slightly weaker than that of E2. Our results indicate that less carcinogenic chlorinated estrogens retaining estrogenic potential could be safer alternatives to the carcinogenic estrogens now in use for HRT.

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