Molecular characterization of the injury‐induced aromatase transcript in the adult zebra finch brain

Wynne, Ryan D.; Maas, Stefan; Saldanha, Colin J.

doi:10.1111/j.1471-4159.2008.05256.x

Cited by 15 publications

(22 citation statements)

References 87 publications

(222 reference statements)

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“…Fourth, our method avoids the effects of injury-induced aromatase. Insertion of the guide cannula for the microdialysis probe induces aromatase around the site of injury, and therefore potentially increases E 2 concentrations at the site of dialysis (Garcia-Segura et al, 1999; Peterson et al, 2001; Peterson et al, 2004; Wynne and Saldanha, 2004; Wynne et al, 2008). Thus, we view the present technique and in vivo microdialysis as complementary approaches to understanding local E 2 levels in the brain and their regulation and function.…”

Section: Discussionmentioning

confidence: 99%

17β-Estradiol levels in male zebra finch brain: Combining Palkovits punch and an ultrasensitive radioimmunoassay

Charlier

Newman

et al. 2010

General and Comparative Endocrinology

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Local aromatization of testosterone into 17β-estradiol (E2) is often required for the physiological and behavioral actions of testosterone. In most vertebrates, aromatase is expressed in a few discrete brain regions. While many studies have measured brain aromatase mRNA or activity, very few studies have measured brain E2 levels, particularly in discrete brain regions, because of technical challenges. Here, we used the Palkovits punch technique to isolate 13 discrete brain nuclei from adult male zebra finches. Steroids were extracted via solid phase extraction. E2 was then measured with an ultrasensitive, specific and precise radioimmunoassay. Our protocol leads to high recovery of E2 (84%) and effectively removes interfering brain lipids. E2 levels were high in aromatase-rich regions such as caudal medial nidopallium and hippocampus. E2 levels were intermediate in the medial preoptic area, ventromedial nucleus of the hypothalamus, lateral and medial magnocellular nuclei of anterior nidopallium, nucleus taeniae of the amygdala, and Area X. E2 levels were largely non-detectable in the cerebellum, HVC, lateral nidopallium and optic lobes. Importantly, E2 levels were significantly lower in plasma than in the caudal medial nidopallium. This protocol allows one to measure E2 in discrete brain regions and potentially relate local E2 concentrations to aromatase activity and behavior.

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Section: Discussionmentioning

confidence: 99%

17β-Estradiol levels in male zebra finch brain: Combining Palkovits punch and an ultrasensitive radioimmunoassay

Charlier

Newman

et al. 2010

General and Comparative Endocrinology

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“…Since only BMP2 and BMP4 were responsive to injury, we chose not to examine BMPs 6 and 7 in this study. The primers used for GAPDH, BMP 2, and BMP 4 were the same for this experiment as those used in the injured versus uninjured experiment (see Table 1, subheading: ‘Semi‐quantitative PCR’ and Wynne et al 2008b).…”

Section: Methodsmentioning

confidence: 99%

Glial aromatization increases the expression of bone morphogenetic protein‐2 in the injured zebra finch brain

Walters

Saldanha

2008

Journal of Neurochemistry

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Abbreviations used: BMP, bone morphogenetic protein; DEPC, diethylpyrocarbonate; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; IACUC, institutional animal care and use committee; MCAO, middle cerebral artery occlusion; NCBI, national center for biotechnology information; PBS, phosphate buffered saline; sqPCR, semi-quantitative polymerase chain reaction. AbstractIn songbirds, brain injury upregulates glial aromatase. The resulting local estrogen synthesis mitigates apoptosis and enhances cytogenesis by poorly understood mechanisms. Bone morphogenetic proteins (BMPs), long studied for their role in neural development, are also neuroprotective and cytogenic in the adult brain. BMPs remain uncharacterized in songbirds, as do the mechanisms regulating their post-injury expression. We first established the expression of BMPs 2, 4, 6, and 7 in the adult zebra finch brain using RT-PCR. Next, we determined the effect of neural insult on BMP expression, by comparing BMP transcripts between injured and uninjured telencephalic hemispheres using semi-quantitative PCR. The expression of BMPs 2 and 4, but not 6 and 7, increased 24 h post-injury. To determine the influence of aromatase on BMP expression, we compared BMP expression following delivery of the aromatase inhibitor Fadrozole or vehicle into contralateral hemispheres. Fadrozole decreased BMP2, but not BMP4, expression, suggesting that aromatization may induce BMP2 expression following injury. Since BMPs are gliogenic and neurotrophic, future studies will test if the neuroprotective and cytogenic effects of aromatase upregulation are mediated by BMP2. Songbirds may be excellent models towards understanding the role of local estrogen synthesis and its downstream mechanisms on neuroprotection and repair. Keywords: estrogen, gliosis, growth factors, neuroprotection, stroke. Bone morphogenetic proteins (BMPs) are diffusible factors critical for the development of the nervous system in vertebrates (Liu and Niswander 2005). They are also expressed in the adult brain (Charytoniuk et al. 2000;Chen et al. 2003;Peretto et al. 2004) where they influence cell proliferation, survival, and fate, particularly following brain injury (Wang et al. 2001;Chang et al. 2002;Brederlau et al. 2004;Chou et al. 2006;Hampton et al. 2007;Colak et al. 2008). Specifically, BMPs 2, 4, 6, and 7, are upregulated following brain damage in rodents (Chang et al. 2003;Hampton et al. 2007;Liu et al. 2007), and exogenous administration of either BMP 6 or BMP 7 limits degeneration and increases recovery of behavioral function following middle cerebral artery occlusion (MCAO) (Liu et al. 2001;Wang et al. 2001;Chang et al. 2003;Chou et al. 2006). In addition to being neuroprotective, BMPs may also enhance gliogenesis and neurogenesis in the post-injury environment (Chou et al. 2006;Xin et al. 2006). Despite their potential benefits and their endogenous response to insult, however, the mechanisms that upregulate BMPs after brain injury have yet to be elucidated.In non In the zebra finch, injury induced aroma...

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“…In the songbird brain, another model for aromatase upregulation in reactive astrocytes after injury, there are only two known promoters in the cyp19 gene, a brain form and an ovarian form [152]. Direct shotgun sequencing of neuronal and injury-induced transcripts of aromatase in the zebra finch brain revealed no differences in any of the exon sequences, suggesting that, if zebra finch cyp19 has multiple promoters, they likely do not result in changes in mRNA splicing or sequence [153]. …”

Section: What Initiates Aromatase Expression In Astroglia?mentioning

confidence: 99%

Neuroprotective actions of brain aromatase

Saldanha¹,

Duncan²,

Walters³

2009

Frontiers in Neuroendocrinology

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152

118

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The steroidal regulation of vertebrate neuroanatomy and neurophysiology includes a seemingly unending list of brain areas, cellular structures and behaviors modulated by these hormones. Estrogens, in particular have emerged as potent neuromodulators, exerting a range of effects including neuroprotection and perhaps neural repair. In songbirds and mammals, the brain itself appears to be the site of injury-induced estrogen synthesis via the rapid transcription and translation of aromatase (estrogen synthase) in astroglia. This induction seems to occur regardless of the nature and location of primary brain damage. The induced expression of aromatase apparently elevates local estrogen levels enough to interfere with apoptotic pathways, thereby decreasing secondary degeneration and ultimately lessening the extent of damage. There is even evidence suggesting that aromatization may affect injury-induced cytogenesis. Thus, aromatization in the brain appears to confer neuroprotection by an array of mechanisms that involve the deceleration and acceleration of degeneration and repair respectively. We are only beginning to understand the factors responsible for the injury-induced transcription of aromatase in astroglia. In contrast, much of the manner in which local and circulating estrogens may achieve their neuroprotective effects has been elucidated. However, gaps in our knowledge include issues about the cell-specific regulation of aromatase expression, steroidal influences of aromatization distinct from estrogen formation, and questions about the role of constitutive aromatase in neuroprotection. Here we describe the considerable consensus and some interesting differences in knowledge gained from studies conducted on diverse animal models, experimental paradigms and preparations towards understanding the neuroprotective actions of brain aromatase.

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Molecular characterization of the injury‐induced aromatase transcript in the adult zebra finch brain

Cited by 15 publications

References 87 publications

17β-Estradiol levels in male zebra finch brain: Combining Palkovits punch and an ultrasensitive radioimmunoassay

17β-Estradiol levels in male zebra finch brain: Combining Palkovits punch and an ultrasensitive radioimmunoassay

Glial aromatization increases the expression of bone morphogenetic protein‐2 in the injured zebra finch brain

Neuroprotective actions of brain aromatase

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