Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions

Acaz‐Fonseca, Estefanía; Ávila-Rodriguez, Marco; Garcia-Segura, Luis Miguel; Barreto, George E.

doi:10.1016/j.pneurobio.2016.06.002

Cited by 101 publications

(93 citation statements)

References 490 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Role of estrogens As stated previously, astrocytes express receptors for estrogens, androgens and progesterone (Garcia-Segura et al 1996a, Melcangi et al 2001, Garcia-Ovejero et al 2005, Acaz-Fonseca et al 2016, with sex steroids possibly participating in the different astroglial responses observed in males and females as a consequence of weight gain and/or obesity. Estrogens are protective against weight gain, adiposity and obesityassociated complications (Stubbins et al 2012, Dakin et al 2015.…”

Section: Differences Between Males and Females In The Astrocytic Respmentioning

confidence: 74%

“…Unfortunately, most studies analyzing the glial response to obesity and HFD have been performed exclusively in males; thus, little is known as to whether sex differences in the hypothalamic glial response to metabolic cues are involved in the different propensities of males and females to develop obesity and its comorbidities. This possibility is suggested by the fact that glial cells present sexually dimorphic characteristics and responses, with these differences being at least partially due to the influence of sex steroids (Chowen et al 1995, Melcangi et al 2001, Acaz-Fonseca et al 2016. Indeed, astrocytes express receptors for estrogens, androgens and progesterone (Pfaff & Keiner 1973, Garcia-Segura et al 1996b, Melcangi et al 2001, Garcia-Ovejero et al 2005 and sex steroids are reported to modulate the glial response to HFD (Louwe et al 2012, Morselli et al 2014.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glial cells and energy balance

Argente-Arizón

Guerra-Cantera

Garcia-Segura

et al. 2017

Journal of Molecular Endocrinology

Self Cite

View full text Add to dashboard Cite

The search for new strategies and drugs to abate the current obesity epidemic has led to the intensification of research aimed at understanding the neuroendocrine control of appetite and energy expenditure. This intensified investigation of metabolic control has also included the study of how glial cells participate in this process. Glia, the most abundant cell type in the central nervous system, perform a wide spectrum of functions and are vital for the correct functioning of neurons and neuronal circuits. Current evidence indicates that hypothalamic glia, in particular astrocytes, tanycytes and microglia, are involved in both physiological and pathophysiological mechanisms of appetite and metabolic control, at least in part by regulating the signals reaching metabolic neuronal circuits. Glia transport nutrients, hormones and neurotransmitters; they secrete growth factors, hormones, cytokines and gliotransmitters and are a source of neuroprogenitor cells. These functions are regulated, as glia also respond to numerous hormones and nutrients, with the lack of specific hormonal signaling in hypothalamic astrocytes disrupting metabolic homeostasis. Here, we review some of the more recent advances in the role of glial cells in metabolic control, with a special emphasis on the differences between glial cell responses in males and females.

show abstract

Section: Differences Between Males and Females In The Astrocytic Respmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Glial cells and energy balance

Argente-Arizón

Guerra-Cantera

Garcia-Segura

et al. 2017

Journal of Molecular Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

“…2) [10, 118-137]. Thus, there is evidence showing that estrogens reduce neuronal death in rodent models of TBI [138] and prevent damage in several pathological conditions affecting the CNS such as cerebral ischemia and Alzheimer’s disease [139].…”

Section: The Cns As a Target For Neuroprotective Estrogenic Compoundsmentioning

confidence: 99%

Astrocytes Mediate Protective Actions of Estrogenic Compounds after Traumatic Brain Injury

et al. 2018

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is a serious public health problem. It may result in severe neurological disabilities and in a variety of cellular metabolic alterations for which available therapeutic strategies are limited. In the last decade, the use of estrogenic compounds, which activate protective mechanisms in astrocytes, has been explored as a potential experimental therapeutic approach. Previous works have suggested estradiol (E2) as a neuroprotective hormone that acts in the brain by binding to estrogen receptors (ERs). Several steroidal and nonsteroidal estrogenic compounds can imitate the effects of estradiol on ERs. These include hormonal estrogens, phytoestrogens and synthetic estrogens, such as selective ER modulators or tibolone. Current evidence of the role of astrocytes in mediating protective actions of estrogenic compounds after TBI is reviewed in this paper. We conclude that the use of estrogenic compounds to modulate astrocytic properties is a promising therapeutic approach for the treatment of TBI.

show abstract

“…Interestingly, even when excluding males from our study, the AR was still co-expressed with GJA1/Cx43. As androgens are known to prevent astrocytosis [29][30][31][32][33][34], our results raise the possibility that in males and females suffering from progressive forms of MS, activation of the AR is somehow defective and fails to downregulate a large set of progliotic genes induced by the TGFB/SMAD1/SMAD2 pathway. This could be due to an age-related decrease of circulating testosterone or of the circulating androgen precursors (Dehydroepiandrosterone and Androstendiol) that can be intracellularly metabolized into testosterone [54][55][56][57].…”

Section: Discussionmentioning

confidence: 80%

“…On the other hand, the androgen receptor (AR), which was also found to co-express with Cx43/GJA1, was previously shown to inhibit reactive astrocytosis under varied CNS conditions [29][30][31][32][33][34]. Of note, AR co-expressed also with Cx43/GJA1 when excluding the 2 male patients from our analysis (data supplement 3).…”

Section: A Unique Set Of Genes Co-upregulate With Cx43/gja1 In Periplmentioning

confidence: 85%

A Unique TGFB1-Driven Genomic Program Links Astrocytosis, Low-Grade Inflammation and Partial Demyelination in Periplaques of Spinal Cords from Progressive Multiple Sclerosis Patients

Nataf¹,

Barritault²,

Pays³

2017

Preprint

View full text Add to dashboard Cite

Abstract:We previously reported that in multiple sclerosis (MS) patients with a progressive form of the disease, spinal cord periplaques extend distance away from plaque borders and are characterized by the co-occurrence of partial demyelination, astrocytosis and low-grade inflammation. However, transcriptomic analyses comparing periplaques to adjacent normal-appearing white matter (NAWM) areas did not allow providing a comprehensive view of molecular events in astrocytes vs oligodendrocytes. Here, we re-assessed our transcriptomic data with the aim of identifying functionally-relevant co-expression networks that would reflect astrocyte vs oligodendrocyte molecular signatures in periplaques. We identified an astrocytosis-related gene module comprising GFAP, the hub gene CX43/GJA1 and a set of transcripts forming a TGFB/SMAD1/SMAD2 genomic signature. Partial demyelination was characterized by a co-expression network which, besides myelin genes, comprised a highly significant number of translation/elongation-related genes. Interestingly, the main oligodendrocyte-related hub we identified was NDRG1, a gene previously shown to be specifically silenced in the NAWM of MS patients. This result indicated that NDRG1 down-regulation could be an important event in the process of periplaque partial demyelination. To establish a putative link between NDRG1 down-regulation and a cytokine/chemokine signature, we then sought to identify cytokine/chemokine genes whose mRNA levels inversely correlated with those of NDRG1. Following this approach we found 5 candidate immune-related genes whose up-regulation associated with NDRG1 down-regulation: TGFB1, PDGFC, . From these results we propose that in the spinal cord of MS patients with progressive forms of the disease, TGFB1 may Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted:

show abstract

Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions

Cited by 101 publications

References 490 publications

Glial cells and energy balance

Glial cells and energy balance

Astrocytes Mediate Protective Actions of Estrogenic Compounds after Traumatic Brain Injury

A Unique TGFB1-Driven Genomic Program Links Astrocytosis, Low-Grade Inflammation and Partial Demyelination in Periplaques of Spinal Cords from Progressive Multiple Sclerosis Patients

Contact Info

Product

Resources

About