Seasonal regression of brain regions involved in the control of birdsong provides a striking and unique opportunity to investigate the mechanisms regulating neuronal degeneration and protection associated with naturally occurring variation in steroid hormones, and the functional consequences of neuroprotection for a learned sensorimotor behavior.
The aims i n this proposal address fundamental issues of hormones as neuroprotective agents in adult brains. These include the role of indirect genomic signaling pathways in hormonal neuroprotection (Aims 1-4), the role of kinase cascades in mediating transynaptic neuroprotective effects of hormones (Aim 3), and whether steroids can have neuroprotective effects in a manner independent of hormone receptors (Aim 2). The birdsong system excels as a model for studies of hormonal mechanisms of neuroprotection. It is a well-defined and tractable neural circuit that shows extreme seasonal patterns of hormone-regulated neuronal regression and protection. These processes of neural degeneration and protection occur with breeding-related hormonal cycles and thus can be studied in vivo without invasive manipulations. This research will advance the field by 1) providing the first evidence in the song system that kinase cascades are """"""""indirect"""""""" genomic contributors to hormonal neuroprotection (Aims 1-4);2) investigating the mechanisms by which hormones act transynaptically to have neuroprotective effects, and whether kinase cascades mediate this effect (Aim 3);and 3) determining whether the contribution of kinase cascades to the neuroprotective effect of steroids requires hormone receptor activation (Aim 2), an issue of continuing uncertainty.
Steroid hormones have potential for use as neuroprotective agents in the treatment of brain injury and a variety of neurodegenerative and mental health disorders. They are also of increasing concern as drugs of abuse. This work will examine the fundamental mechanisms by which these potent hormones act to protect the brain.
|Brenowitz, Eliot A; Remage-Healey, Luke (2016) It takes a seasoned bird to be a good listener: communication between the sexes. Curr Opin Neurobiol 38:12-7|
|Cohen, Rachel E; Macedo-Lima, Matheus; Miller, Kimberly E et al. (2016) Adult Neurogenesis Leads to the Functional Reconstruction of a Telencephalic Neural Circuit. J Neurosci 36:8947-56|
|Brenowitz, Eliot A; Larson, Tracy A (2015) Neurogenesis in the adult avian song-control system. Cold Spring Harb Perspect Biol 7:|
|Larson, Tracy A; Lent, Karin L; Bammler, Theo K et al. (2015) Network analysis of microRNA and mRNA seasonal dynamics in a highly plastic sensorimotor neural circuit. BMC Genomics 16:905|
|Brenowitz, Eliot A (2015) Transsynaptic trophic effects of steroid hormones in an avian model of adult brain plasticity. Front Neuroendocrinol 37:119-28|
|Small, Thomas W; Brenowitz, Eliot A; Wojtenek, Winfried et al. (2015) Testosterone Mediates Seasonal Growth of the Song Control Nuclei in a Tropical Bird. Brain Behav Evol 86:110-21|
|Brenowitz, Eliot A; Zakon, Harold H (2015) Emerging from the bottleneck: benefits of the comparative approach to modern neuroscience. Trends Neurosci 38:273-8|
|Larson, Tracy A; Thatra, Nivretta M; Lee, Brian H et al. (2014) Reactive neurogenesis in response to naturally occurring apoptosis in an adult brain. J Neurosci 34:13066-76|
|Brenowitz, E A (2013) Testosterone and brain-derived neurotrophic factor interactions in the avian song control system. Neuroscience 239:115-23|
|Larson, Tracy A; Wang, Tsu-Wei; Gale, Samuel D et al. (2013) Postsynaptic neural activity regulates neuronal addition in the adult avian song control system. Proc Natl Acad Sci U S A 110:16640-4|
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