A Quantification of the Injury‐Induced Changes in Central Aromatase, Oestrogenic Milieu and Steroid Receptor Expression in the Zebra Finch

Abstract

In songbirds and mammals, brain injury results in the up-regulation of aromatase (oestrogen synthase) expression in astroglia. The resulting presumed synthesis of neural oestradiol (E2 ) has neuroprotective effects including a decrease in neurodegeneration, neuroinflammation and apoptosis. The development of therapeutic tools that exploit oestrogenic neuroprotection in the treatment of neurotrauma requires a precise quantification of the endogenous changes in neural aromatase and E2 following brain injury. Surprisingly, the expected increase in neural oestrogens following brain injury has not been demonstrated. Furthermore, we are just beginning to unravel the mechanisms behind the protective effects of centrally synthesised E2 . In the present study, levels of aromatase immunoprotein, neural E2 and steroid receptor mRNA were quantified in adult male and female zebra finches 48 h following a unilateral penetrating brain injury. Both aromatase and E2 were up-regulated in the injured hemisphere of the brain compared to the uninjured hemisphere, demonstrating for the first time a robust increase in neural E2 levels following injury. We did not detect an effect of injury on mRNA expression of the oestrogen receptors (ER)-α, ER-β or GPER-1, but observed a significant decrease in androgen receptor transcription in the injured lobe relative to the contralateral uninjured hemisphere. We conclude that mechanical damage causes a dramatic increase in local aromatisation, and the resultant high levels of central E2 are available to modulate steroid sensitive targets. Studies using alternate methods of receptor detection and/or time points may be necessary to understand the complete suite of mechanisms underlying the neuroprotective effects of induced oestrogen synthesis in this animal model.

Clustered organization and region‐specific identities of estrogen‐producing neurons in the forebrain of Zebra Finches (Taeniopygia guttata)

“…Region-specific staining pattern with this antibody in the present study matches that previously reported (Saldanha et al, 2000). Immunoblots showing a single band have been more recently published for this same antibody, confirming its viability (Rohmann, Schlinger, & Saldanha, 2007;Mehos, Nelson, & Saldanha, 2016) 2. Anti-calbindin antibody (Sigma Aldrich, C9848, RRID: AB_476894) was raised against bovine kidney calbindin-D (manufacturer's technical information).…”

Molecular mechanisms and cellular events involved in the neuroprotective actions of estradiol. Analysis of sex differences

“…In addition, under conditions of brain injury, including traumatic brain injury, cerebral ischemia or excitotoxicity, the expression of the enzyme is induced in astrocytes (Garcia-Segura et al, 1999;Saldanha et al, 2009;Zhang et al, 2014;Pedersen et al, 2018) together with an increase in brain aromatase activity (Garcia-Segura et al, 1999) and brain estradiol levels (Q.G. Zhang et al, 2014;Mehos et al, 2016).…”

Exogenous progesterone is neuroprotective following injury to the male zebra finch brain

“…The p38α‐MAPK14 is implicated in cell survival/apoptosis, proliferation, differentiation, migration, mRNA stability, and inflammatory response in diverse cell types through a variety of different target molecules (Young, ). MK2 is one of the well‐studied downstream targets of p38α‐MAPK14 and together they have downstream targets with cAMP response element‐binding protein (CREB) and cyclooxygenase 2 (COX‐2), both of which have been implicated in the steroidal response to injury in the zebra finch brain (Klores et al, ; Mehos et al, ; Pedersen et al, ). The p38α‐MAPK14 activation also results in TNF‐α biosynthesis following activation of MAPKAPK‐2 (Gurgis et al, ; Martinez Calejman et al, ; Mercau et al, ).…”