Neuroinflammation and neurosteroidogenesis: Reciprocal modulation during injury to the adult zebra finch brain

Abstract

Estrogens like estradiol (E2) via their receptors are pluripotent steroid hormones that exert a profound influence on the developing and adult brain in many vertebrates. In songbirds and mammals, acute brain injury resulting from mechanical damage, anoxia and ischemia rapidly upregulates aromatase and E2 synthesis. Interestingly, this E2 provision occurs due to the induction of aromatase expression in reactive astrocytes in areas surrounding brain injury. The resultant increase in E2 is neuroprotective with established influences on apoptosis, gliosis, cytogenesis, neurogenesis and neuroinflammation. Correspondingly, E2 decreases secondary damage following acute brain trauma and may improve recovery. Until very recently however, the signals responsible for the induction of astrocytic aromatase expression in reactive astrocytes were unknown. In the current review, we discuss what is known about the role of astrocytic E2 in neuroprotection with a particular emphasis on a recently discovered interaction between neuroinflammatory and steroidogenic signaling in the zebra finch. We first describe the role of acute inflammatory signaling in the regulation of astrocytic aromatase and central E2 levels. Next, we discuss the emerging role of central E2 in the control of chronic neuroinflammation. Finally, we provide a framework for further work investigating the important role of the interaction between inflammatory and steroidogenic signaling in the protection of neural circuits and behavior following traumatic brain injury (TBI). We also highlight dimorphisms that point to important aspects of sex-specific pathways that underlie the interactions of neuroinflammation and neurosteroidogenesis.