Activation of the peripheral immune system regulates neuronal aromatase in the adult zebra finch brain

Abstract

Estradiol provision via neural aromatization decreases neuro-inflammation and –degeneration, but almost nothing is known about the interactions between the peripheral immune system and brain aromatase. Given the vulnerability of the CNS we reasoned that brain aromatization may protect circuits from the threats of peripheral infection; perhaps shielding cells that are less resilient from the degeneration associated with peripheral infection or trauma. Lipopolysaccharide (LPS) or vehicle was administered peripherally to adult zebra finches and sickness behavior was recorded 2 or 24 hours later. The central transcription of cytokines and aromatase was measured, as were telencephalic aromatase activity and immunoreactive aromatase (24 hour time point only). Two hours post LPS, sickness-like behaviors increased, the transcription of IL-1β was higher in both sexes, and TNFα was elevated in females. 24 hours post-LPS, the behavior of LPS birds was similar to controls, and cytokines had returned to baseline, but aromatase mRNA and activity were elevated in both sexes. Immunocytochemistry revealed greater numbers of aromatase-expressing neurons in LPS birds. These data suggest that the activation of the immune system via peripheral endotoxin increases neuronal aromatase; a mechanism that may rapidly generate a potent anti-neuroinflammatory steroid in response to peripheral activation of the immune system.

Acute exposure to 4-OH-A, not PCB1254, alters brain aromatase activity but does not adversely affect growth in zebrafish

“…The assay used in the present study was similar to that described previously (Ankley et al, 2002;Balthazart et al, 2006;Cheshenko et al, 2008;Hinfray et al, 2006;Pedersen et al, 2017) with minor modifications. We optimized original protocols for microsomes (Roselli and Resko, 1991), using homogenates of thawed whole adult zebrafish brains randomly sampled in triplicate (3/tube), with 3 tubes/treatment (2 replicate tubes, 1 assessing nonspecific background radioactivity).…”

Female presence does not increase testosterone but still ameliorates sickness behaviours in male Japanese quail

“…production of steroids in the brain) could still have a role in modulating sickness behaviours. For example, in zebra finches, the expression of neuronal aromatase (an enzyme that converts testosterone to estradiol) increases after a peripheral injection with LPS [ 27 ]. Furthermore, if this aromatase production is inhibited, neuroinflammation is prolonged [ 28 ].…”

Inflammation Induced by Natural Neuronal Death and LPS Regulates Neural Progenitor Cell Proliferation in the Healthy Adult Brain

“…For example, following mechanical injury to the zebra finch telencephalon, activated astroglia initially promote a proinflammatory-like response through expression of the cytokines interleukin-1b and interleukin-6 increases (Duncan and Saldanha, 2011), but subsequently "switch" to a more neuroprotective response by 20 h through increased expression of aromatase, the enzyme that facilitates estradiol synthesis from T (Duncan and Saldanha, 2011). Likewise, peripheral LPS administration in zebra finches increases transcription of aromatase in the telencephalon by 24 h postinjection (Pedersen et al, 2017b). This increase in LPS-induced aromatase expression is reduced with central administration of the anti-inflammatory drug indomethacin (Pedersen et al, 2017a).…”