Neuroinflammation induces glial aromatase expression in the uninjured songbird brain - PubMed (original) (raw)

Neuroinflammation induces glial aromatase expression in the uninjured songbird brain

Kelli A Duncan et al. J Neuroinflammation. 2011.

Abstract

Background: Estrogens from peripheral sources as well as central aromatization are neuroprotective in the vertebrate brain. Under normal conditions, aromatase is only expressed in neurons, however following anoxic/ischemic or mechanical brain injury; aromatase is also found in astroglia. This increased glial aromatization and the consequent estrogen synthesis is neuroprotective and may promote neuronal survival and repair. While the effects of estradiol on neuroprotection are well studied, what induces glial aromatase expression remains unknown.

Methods: Adult male zebra finches (Taeniopygia guttata) were given a penetrating injury to the entopallium. At several timepoints later, expression of aromatase, IL-1β-like, and IL-6-like were examined using immunohistochemistry. A second set of zebra birds were exposed to phytohemagglutinin (PHA), an inflammatory agent, directly on the dorsal surface of the telencephalon without creating a penetrating injury. Expression of aromatase, IL-1β-like, and IL-6-like were examined using both quantitative real-time polymerase chain reaction to examine mRNA expression and immunohistochemistry to determine cellular expression. Statistical significance was determined using t-test or one-way analysis of variance followed by the Tukey Kramers post hoc test.

Results: Following injury in the zebra finch brain, cytokine expression occurs prior to aromatase expression. This temporal pattern suggests that cytokines may induce aromatase expression in the damaged zebra finch brain. Furthermore, evoking a neuroinflammatory response characterized by an increase in cytokine expression in the uninjured brain is sufficient to induce glial aromatase expression.

Conclusions: These studies are among the first to examine a neuroinflammatory response in the songbird brain following mechanical brain injury and to describe a novel neuroimmune signal to initiate aromatase expression in glia.

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Figures

Figure 1

Figure 1

Interleukin antibody specificity and cellular characterization. Western blot analysis of IL-1β-like (A) and IL-6-like (B). Representative high power magnification of IL-1β-like (C) and IL-6-like (G) immunoreactive cells in the zebra finch brain. IL-1β-like (D-F) and IL-6-like (H-J) cells around injury coexpress microglial proteins (yellow, (F, J). Panels (D-E) and (H-I) reveal the identical field of cells viewed through the green (microglia) and red (IL-1β-like and IL-6-like) channels alone.

Figure 2

Figure 2

Temporal expression of IL-1β-like immunoreactive cells (A), IL-6-like (B), and Aromatase (C) following mechanical injury in the zebra finch brain. Data are represented as mean ± SEM. Data not connected by the same letter are significantly different (p < .05).

Figure 3

Figure 3

Bar graph depicting the mean uncalibrated optical density (OD) for IL-1β-like (A) and IL-6-like (B) immunoreactive cells at 6 h and 24 h following treatment with PHA. (C) Representative sections depicting the localization of IL-1-like (top) and IL-6-like -ir cells (bottom) following PHA treatment. * denotes a significant difference between treatment and saline.

Figure 4

Figure 4

Bar graph showing the mean ± SEM in ΔCt values (normalized against GAPDH, (A)) and fold change (B) between saline and PHA treated telencephalons for aromatase. Fold change in expression was calculated using the double delta Ct method assuming 100% efficiency. * denotes a significant difference between treatment and saline.

Figure 5

Figure 5

Representative sections from male zebra finches for aromatase immunoreactivity (Arom-ir) following exposure to PHA and saline. (A) Low power magnification of Arom-ir following exposure to PHA (left) and saline (right). (B) Higher power magnification of Arom-ir cells after exposure to PHA. (C) High power magnification exhibiting the typical cellular morphology and structure of Arom-ir cells following exposure to PHA. (D) Control section showing that normal Arom-ir is not affected by treatment with PHA (left) or saline (right). (E) High power magnification showing neuronal expression of aromatase.

Figure 6

Figure 6

Panels (A) and (B) reveal the identical field of cells viewed through the red (aromatase (B)) and green (vimentin (C)) channels alone. Aromatase cells coexpress glial proteins (yellow, C).

Figure 7

Figure 7

Representative sections black-white inverted following cell degeneration assay (TUNEL). TUNEL- labeled cells were not present in tissue exposed to PHA (A). PHA tissue was run concurrently with injured tissue to serve as a positive control (B).

Figure 8

Figure 8

Proposed model of aromatase mediated neuroprotection following injury or damage to the brain.

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