Testosterone Protects Mitochondrial Function and Regulates Neuroglobin Expression in Astrocytic Cells Exposed to Glucose Deprivation.

Nicolas Toro-Urrego,George E Barreto,Luis M Garcia-Segura,Valentina Echeverria

doi:10.3389/fnagi.2016.00152

Abstract

Testosterone is a hormone that has been shown to confer neuroprotection from different insults affecting the central nervous system (CNS). Testosterone induces this protection by different mechanisms that include the activation of anti-apoptotic pathways that are directly implicated in neuronal survival. However, little attention has been devoted to its actions on glial cells. In the present study, we have assessed whether testosterone exerts protection in a human astrocyte cell model, the T98G cells. Our results indicate that testosterone improves cell survival and mitochondrial membrane potential and reduces nuclear fragmentation and reactive oxygen species (ROS) generation. These effects were accompanied by a positive regulation of neuroglobin, an oxygen-binding and sensor protein, which may serve as a regulator of ROS and nitrogen reactive species (NOS), and these protective effects of testosterone may be at least in part mediated by estradiol and DHT. In conclusion, these findings suggest that astroglia may mediate some of the protective actions of testosterone in the brain upon pathological conditions.

Highlights

Testosterone, a gonadal hormone, modulates aggressive and sexual behavior (Christiansen, 2001), has anxiolytic and antidepressant-like effects (Carrier et al, 2015), affects cognition (Cherrier, 2005), and regulates synaptic plasticity in the brain (Hatanaka et al, 2015)
Our results indicated that estradiol improved cell viability (Figure 7A, p < 0.0001) and mitochondrial membrane potential (p < 0.0001), reduced O2-production (Figure 7C, p < 0.0002), and H2O2 levels (Figure 7D, p < 0.0164) and significantly increased mitochondrial mass (Figure 7E, p < 0.0011) in comparison to BSS0
It is thought that protecting astrocytes function might be a promissory strategy to promote neuronal survival following various brain insults

Summary

Introduction

Testosterone, a gonadal hormone, modulates aggressive and sexual behavior (Christiansen, 2001), has anxiolytic and antidepressant-like effects (Carrier et al, 2015), affects cognition (Cherrier, 2005), and regulates synaptic plasticity in the brain (Hatanaka et al, 2015). Testosterone has been shown to prevent neuronal cell death, to improve memory after damage (Fanaei et al, 2014), and to regulate the activation and reactivity of glial cells upon brain injury (Barreto et al, 2007). Improvement of mitochondrial function may be one of the mechanisms involved in the protective actions of testosterone in the brain. Testosterone enhances the functional recovery in animals subjected to cerebral ischemia by promoting the increase of BDNF, antioxidant defense/activity and neurogenesis (Chisu et al, 2006; Fanaei et al, 2014).

Methods

Results

Conclusion