Neuroinflammation induces glial aromatase expression in the uninjured songbird brain

Duncan, Kelli A.; Saldanha, Colin J.

doi:10.1186/1742-2094-8-81

Cited by 54 publications

(42 citation statements)

References 60 publications

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“…The ZF brain produces a dramatic and robust increase in glial cells surrounding the injury site (Duncan et al, ; Saldanha et al, ). These glial cells are capable of altering steroid hormone sensitivity and have shown that steroid hormones are rapidly upregulated following injury and potentially serve to decrease neuronal damage (Duncan and Saldanha, ; Duncan et al, ; Walters et al, ). Although it is hard to directly compare across experimental protocols, treatments, and dependent measures, the data suggest that the steroidal response to injury is robust enough to completely dampen the wave of secondary degeneration that is diagnostic of severe brain trauma in humans and other mammals (Duncan et al, ; Pedersen et al, ; Wynne et al, ).…”

Section: Introductionmentioning

confidence: 99%

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

Blackshear

Giessner

Hayden

et al. 2017

J of Neuroscience Research

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The use of progesterone following brain injury has a controversial history. On one hand, some lab-based models have showed progesterone as being neuroprotective, but on the other, clinical trials have showed quite the opposite. One of many complaints that arose from this discrepancy was the lack of a diverse pool of animal models and paradigms employed during the preclinical phase. However, over the past decade, the zebra finch has emerged as an optimal organism for the study of steroid-mediated neuroprotection. Following an injury, steroid hormones and receptors are upregulated, serving to decrease neuroinflammation and overall damage to the brain. As compared to other vertebrate models, zebra finches can upregulate expression of both estrogens and androgens at a faster and more robust response, suggesting that vertebrates differ in their neuroprotective mechanisms and timing following injury. Therefore, to expand the types organisms studied in pre-clinical trials, we chose to use zebra finches. While the majority of work in the zebra finch brain has focused on estrogens and androgens, we sought to clarify the role of progesterone following injury. Adult male zebra finches were given daily injections of progesterone following a penetrating injury and then were assessed for the size of injury and expression of various genes associated with neuroinflammation and cell survival. Treatment with progesterone decreased the injury size in zebra finches over controls and increased expression of various genes associated with cell survival and neuroinflammation. These data suggest that progesterone does mediate neuroprotection, most likely through the alteration of neuroinflammatory and cell survival pathways.

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Section: Introductionmentioning

confidence: 99%

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

Blackshear

Giessner

Hayden

et al. 2017

J of Neuroscience Research

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“…Supporting the neuroprotective role of steroid hormones, Roselli (27) reported that brain aromatase is neuroprotective. Indeed, increased aromatase expression is observed following neural injury and neuroinflammation (28,29). Therefore, transcriptional activation of aromatase might prevent neuronal cell death.…”

Section: Discussionmentioning

confidence: 98%

Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices

2014

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Hippocampal functions are influenced by steroid hormones, such as testosterone and estradiol. It has been demonstrated that hippocampus-derived steroid hormones play important roles in neuronal protection and synapse formation. Our research groups have demonstrated that estradiol is de novo synthesized in the rat hippocampus. However, the mechanism(s) regulating this synthesis remains unclear. It has been reported that tributyltin, an environmental pollutant, binds to the retinoid X receptor (RXR) and modifies estrogen synthesis in human granulosa-like tumor cells. This compound can penetrate the blood brain barrier, and tends to accumulate in the brain. Based on these facts, we hypothesized that tributyltin could influence the hippocampal estradiol synthesis. A concentration of 0.1 μM tributyltin induced an increase in the mRNA content of P450(17α) and P450arom in hippocampal slices, as determined using real-time PCR. The transcript levels of other steroidogenic enzymes and a steroidogenic acute regulatory protein were not affected. The estradiol level in rat hippocampal slices was subsequently determined using a radioimmunoassay. We found that the estradiol synthesis was stimulated by ∼2-fold following a 48-h treatment with 0.1 μM tributyltin, and this was accompanied by transcriptional activation of P450(17α) and P450arom. Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the transcription of specific steroidogenic enzymes.

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“…First, following the canonical pathway, increased NFκB signaling results in a further increase in cytokine expression causing secondary damage and additional tissue destruction [11]. Second, a neuroprotective pathway is activated where NFκB signaling increases gliosis which results in an increase in aromatase activity in astrocytes [22, 25, 26, 29, 48] but also increased androgen receptors in microglia [45]. Upregulation of these steroids results in inhibition of neuroinflammation by decreasing COX-2 and PGE 2 action [22] and by decreasing NFκB and IκB expression.…”

Section: Discussionmentioning

confidence: 99%

“…Blocking aromatase and thus estrogen production leads to an exacerbation of the inflammation [22] and injury size [27, 28]. Furthermore, glial aromatase expression is induced via neuroinflammation [25] and we hypothesize that this induction is mediated by TNF-α specifically. These data suggest that estrogens interacting with TNF-α and subsequently NFκB may be a potential target for neuroinflammatory mediation.…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between Estrogen Withdrawal and NFκB Signaling following Penetrating Brain Injury

Cook

Hung

Duncan

2018

Neuroimmunomodulation

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Objectives: Characterized by neuroinflammation, traumatic brain injury (TBI) induces neuropathological changes and cognitive deficits. Estrogens are neuroprotective by increasing cell survival and this increase is mediated by a decrease in neuroinflammation. To further explore the relationship between estrogens, brain injury, and neuroinflammation, we examined the expression of the IKK/NFκB complex. The IKK/NFκB complex is a pleiotropic regulator of many cellular signaling pathways linked to inflammation, as well as three major cytokines (IL-1β, IL-6, and TNF-α). We hypothesized that NFκB expression would be upregulated following injury and that this increase would be exacerbated when circulating estrogens were decreased with fadrozole (aromatase inhibitor). Methods: Using adult zebra finches, we first determined the expression of major components of the NFκB complex (NFκB, IκB-α, and IκB-β) following injury using qPCR. Next, male and female finches were collected at 2 time points (2 or 24 h after injury) and brain tissue was analyzed to determine whether NFκB expression was differentially expressed in males and females at either time point. Finally, we examined how the expression of NFκB changed when estrogen levels were decreased immediately after injury. Results: Our study documented an increase in the expression of the major components of the NFκB complex (NFκB, IκB-α, and IκB-β) following injury. Decreasing estrogen levels resulted in a surprising decrease in the NFκB complex studied here. Discussion: These data further expand the model of how estrogens and other steroid hormones interact with the inflammatory pathways following injury and may prove beneficial when developing therapies for treatment of TBI.

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Neuroinflammation induces glial aromatase expression in the uninjured songbird brain

Cited by 54 publications

References 60 publications

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

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

Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices

Crosstalk between Estrogen Withdrawal and NFκB Signaling following Penetrating Brain Injury

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