Estradiol Regulates PSA-NCAM Expression and Connectivity of O-LM Interneurons in The Hippocampus of Adult Female Mice

2021 ◽  
Author(s):  
Marta Perez-Rando ◽  
Ramon Guirado ◽  
Guillermina Tellez-Merlo ◽  
Hector Carceller ◽  
Juan Nacher

The estrous cycle is caused by the changing concentration of ovarian hormones, particularly 17β-Estradiol, a hormone whose effect on excitatory circuits has been extensively reported. However, fewer studies have tried to elucidate how this cycle, or this hormone, affects the plasticity of inhibitory networks and the structure of interneurons. Among these cells, somatostatin expressing O-LM neurons of the hippocampus have a role in the modulation of theta oscillations, and they receive direct input from the entorhinal cortex, which place them in the center of hippocampal function. In this study, we report that the expression of PSA-NCAM in the hippocampus, a molecule involved in the plasticity of somatostatin expressing interneurons in the adult brain, fluctuated through the different stages of the estrous cycle. Likewise, these stages and the expression of PSA-NCAM affected the density of dendritic spines of O-LM cells. We also describe that 17β-Estradiol replacement of adult ovariectomized female mice caused an increase of the perisomatic inhibitory puncta on O-LM interneurons, as well as an increase in their axonal bouton density. Interestingly, this treatment also induced a decrease in their dendritic spine density, specifically in O-LM interneurons lacking PSA-NCAM expression. Finally, using an ex vivo real-time assay with entorhino-hippocampal organotypic cultures we show that this hormone decreased the dynamics in spinogenesis, altogether highlighting the modulatory effect that 17β-Estradiol has on inhibitory circuits.

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Yuefei Huang ◽  
Tham M Yao ◽  
Paul Loutraris ◽  
Isis K Rangel ◽  
Pei Yee Ting ◽  
...  

Lysine-Specific Demethylase1 (LSD1) is an epigenetic factor modulated by salt intake. Previously, we documented the male heterozygote LSD1 knockout mice (LSD1+/-) had dysregulation of aldosterone (ALDO) production on a liberal salt diet (1.6% Na+) associated with salt-sensitive hypertension. This study assessed if: 1) female LSD1+/- mice have a similar phenotype; and 2) the effect of aging on this phenotype. Methods: Female LSD1+/- and wild type mice (LSD1+/+) were randomly assigned for sacrifice at the ages of 18-week, 52-week, and 75-week and the following were assessed at each time point: blood pressure (BP); plasma renin activity (PRA) and ALDO; urine albumin; and ex vivo ALDO production from isolated adrenal zona glomerulosa cells. Results: BP and urine albumin in the LSD1+/- compared to the LSD1+/+ were not different at any age (Table). However, the LSD1+/- had greater ALDO/PRA ratios at 18 weeks compared with the LSD1+/+, but lower ALDO levels and ex vivo ALDO production at 52 and 75 weeks. Associated with this phenotype, the LSD1+/- showed significantly higher rate of all-cause mortality than the LSD1+/+. Conclusion: Lack of LSD1 caused dysregulation of ALDO production in both male and female mice. But the cardiovascular outcomes are different. The LSD1+/- females in contrast to males do not develop hypertension or albuminuria even at 75 weeks of age. However, the females do die at a faster rate than the males of a variety of causes. Thus, there is considerable sexual dimorphism in the pathogenesis of cardiovascular outcomes associated with dysregulation of adrenal ALDO production mediated by lack of LSD1.


2018 ◽  
Vol 9 ◽  
Author(s):  
Nancy M. Lainez ◽  
Carrie R. Jonak ◽  
Meera G. Nair ◽  
Iryna M. Ethell ◽  
Emma H. Wilson ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Kanae Mukai ◽  
Yukari Nakajima ◽  
Tamae Urai ◽  
Emi Komatsu ◽  
Kana Takata ◽  
...  

Estrogen replacement promotes cutaneous wound healing in 8–10-week young ovariectomized female mice. However, research using aged ovariectomized female mice has not been reported, to the best of our knowledge. Therefore, we investigated the effect of 17β-estradiol on cutaneous wound healing using 24-week middle-aged ovariectomized female mice. Twenty-week-old female mice were divided into three groups: medication with 17β-estradiol after ovariectomy (OVX + 17β-estradiol), ovariectomy (OVX), and sham (SHAM). After 4 weeks, the mice received two full-thickness wounds. Then, the OVX + 17β-estradiol group was administered 17β-estradiol at 0.01 g/day until healing. The ratio of wound area in the OVX + 17β-estradiol group was significantly decreased compared with that in the OVX group. The numbers of neutrophils and macrophages in the OVX + 17β-estradiol group were significantly smaller than those in the OVX group. In addition, the ratio of myofibroblasts in the OVX + 17β-estradiol group was significantly higher than that in the OVX group. These data suggested that exogenous continuous 17β-estradiol administration promotes cutaneous wound healing in 24-week OVX female mice by reducing wound area, shortening inflammatory response, and promoting wound contraction. However, it is unclear whether the effect of exogenous estrogen on wound healing outweighs the delay of wound healing due to advanced age.


2019 ◽  
Vol 39 (1) ◽  
pp. 20-29
Author(s):  
Nayeli Meléndez-García ◽  
Fátima García-Ibarra ◽  
Patricia Bizarro-Nevares ◽  
Marcela Rojas-Lemus ◽  
Nelly López-Valdez ◽  
...  

Vanadium is a metal present in particulate matter and its reprotoxic effects have been demonstrated in males and pregnant females in animal models. However, the effects of this metal on the reproductive organs of nonpregnant females have not been sufficiently studied. In a vanadium inhalation model in nonpregnant female mice, we found anestrous and estrous cycle irregularity, as well as low serum concentrations of 17β-estradiol and progesterone. A decrease in the diameter of secondary and preovulatory follicles, as well as a thickening of the myometrium and endometrial stroma, was observed in the vanadium-treated mice. There was no difference against the control group with respect to the presence of the estrogen receptor α in the uterus of the animals during the estrous stage. Our results indicate that when vanadium is administered by inhalation, effects are observed on the female reproductive organs and the production of female sex hormones.


2019 ◽  
Vol 20 (2) ◽  
pp. 455 ◽  
Author(s):  
Felix Beyer ◽  
Iria Samper Agrelo ◽  
Patrick Küry

The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell replacement generally remains insufficient, undirected, or lost cell types are not properly generated. This limitation also accounts for the myelin repair capacity that still constitutes the default regenerative activity at least in inflammatory demyelinating conditions. Ever since the discovery of endogenous neural stem cells (NSCs) residing within specific niches of the adult brain, as well as the description of procedures to either isolate and propagate or artificially induce NSCs from various origins ex vivo, the field has been rejuvenated. Various sources of NSCs have been investigated and applied in current neuropathological paradigms aiming at the replacement of lost cells and the restoration of functionality based on successful integration. Whereas directing and supporting stem cells residing in brain niches constitutes one possible approach many investigations addressed their potential upon transplantation. Given the heterogeneity of these studies related to the nature of grafted cells, the local CNS environment, and applied implantation procedures we here set out to review and compare their applied protocols in order to evaluate rate-limiting parameters. Based on our compilation, we conclude that in healthy CNS tissue region specific cues dominate cell fate decisions. However, although increasing evidence points to the capacity of transplanted NSCs to reflect the regenerative need of an injury environment, a still heterogenic picture emerges when analyzing transplantation outcomes in injury or disease models. These are likely due to methodological differences despite preserved injury environments. Based on this meta-analysis, we suggest future NSC transplantation experiments to be conducted in a more comparable way to previous studies and that subsequent analyses must emphasize regional heterogeneity such as accounting for differences in gray versus white matter.


2012 ◽  
Vol 87 (2-3) ◽  
pp. 319-327 ◽  
Author(s):  
Silvarosa Grassi ◽  
Adele Frondaroli ◽  
Mariangela Scarduzio ◽  
Cristina V. Dieni ◽  
Gabriele Brecchia ◽  
...  

1983 ◽  
Vol 17 (2) ◽  
pp. 233-236 ◽  
Author(s):  
A. Marchlewska-Koj ◽  
M. Kruczek ◽  
E. Toch
Keyword(s):  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Marco Bocchio ◽  
Claire Gouny ◽  
David Angulo-Garcia ◽  
Tom Toulat ◽  
Thomas Tressard ◽  
...  

Abstract The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as ‘hubs’ by orchestrating population synchrony. However, their adult fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only operate as hubs during development, but also maintain distinct morpho-physiological and connectivity profiles, including a bias for long-range targets and local excitatory inputs. In vivo, ebGABAs are activated during locomotion, correlate with CA1 cell assemblies and display high functional connectivity. Hence, ebGABAs are specified from birth to ensure unique functions throughout their lifetime. In the adult brain, this may take the form of a long-range hub role through the coordination of cell assemblies across distant regions.


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