Abstract
Mature brain derived neurotrophic factor (BDNF) plays critical roles in development of brain structure and function, including neurogenesis, axon growth, cell survival and processes associated with learning. Expression of this peptide is regulated by estradiol (E2). The zebra finch song system is sexually dimorphic – only males sing and the brain regions controlling song are larger and have more cells in males compared to females. Masculinization of this system is partially mediated by E2, and earlier work suggests that BDNF with its high affinity receptor TrkB may also influence this development. The present study evaluated expression of multiple forms of both BDNF and TrkB in the developing song system in juvenile males and females treated with E2 or a vehicle control. Using immunohistochemistry and Western blot analysis, BDNF was detected across the song nuclei of 25-day-old birds. Westerns allowed the pro- and mature forms of BDNF to be individually identified, and proBDNF to be quantified. Several statistically significant effects of sex existed in both the estimated total number of BDNF+ cells and relative concentration of proBDNF, varying across the regions and methodologies. E2 modulated BDNF expression, although the specific nature of the regulation depended on brain region, sex and the technique used. Similarly, TrkB (both truncated and full-length isoforms) was detected by Western blot in the song system of juveniles of both sexes, and expression was regulated by E2. In the context of earlier research on these molecules in the developing song system, this work provides a critical step in describing specific forms of BDNF and TrkB, and how they can be mediated by sex and E2. As individual isoforms of each can have opposing effects on mechanisms, such as cell survival, it will now be important to investigate in depth their specific functions in song system maturation.
Highlights
Brain-derived neurotrophic factor (BDNF) is critical for diverse aspects of brain development and function, including cell survival, axon guidance, synaptic connectivity, dendritic arborization, longterm potentiation, and memory consolidation
BDNF binds to two types of receptors in the brain, with highaffinity to tyrosine kinase B (TrkB; [4,5,6]) and with low-affinity to the p75 receptor [7,8]
Because potential effects of E2 on TrkB have not been reported, we investigated this protein in song nuclei using Western blot analyses to distinguish between the full length and truncated forms of TrkB
Summary
Brain-derived neurotrophic factor (BDNF) is critical for diverse aspects of brain development and function, including cell survival, axon guidance, synaptic connectivity, dendritic arborization, longterm potentiation, and memory consolidation. The peptide is synthesized via precursors, prepro- pro-BDNF, which is cleaved and secreted in the mature form. This secretion can occur in a regulated, activity dependent manner from either axons or dendrites ( having anterograde or retrograde action), or via more passive, constitutive mechanisms [1,2,3]. The full-length form (TrkB-FL) contains a cytoplasmic domain that activates a variety of signaling cascades [10]. It is through this receptor that the vast majority of the enhancing effects on neuronal structure and function are elicited. An alternatively spliced variant (truncated; TrkB-T) lacks this intracellular portion and generally inhibits BDNF action (reviewed in [11]; see below)
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