Abstract
The neurotrophins are neuropeptides that are potent regulators of neurite growth and survival. Although mainly studied in the brain and nervous system, recent reports have shown that neurotrophins are expressed in multiple target tissues and cell types throughout the body. Additionally, dysregulation of neurotrophins has been linked to several disease conditions including Alzheimer's, Parkinson's, Huntington's, psychiatric disorders, and cancer. Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family that elicits its actions through the neurotrophic tyrosine receptor kinase type 2 (Ntrk2). Together BDNF and Ntrk2 are capable of activating the adhesion, angiogenesis, apoptosis, and proliferation pathways. These pathways are prominently involved in reproductive physiology, yet a cross-species examination of BDNF and Ntrk2 expression in the mammalian uterus is lacking. Herein we demonstrated the conserved nature of BDNF and Ntrk2 across several mammalian species by mRNA and protein sequence alignment, isolated BDNF and Ntrk2 transcripts in the uterus by Real-Time PCR, localized both proteins to the glandular and luminal epithelium, vascular smooth muscle, and myometrium of the uterus, determined that the major isoforms expressed in the human endometrium were pro-BDNF, and truncated Ntrk2, and finally demonstrated antibody specificity. Our findings suggest that BDNF and Ntrk2 are transcribed, translated, and conserved across mammalian species including human, mouse, rat, pig, horse, and the bat.
Highlights
Brain derived neurotrophic factor (BDNF) is one member of the neurotrophin family of secreted growth factors which comprises nerve growth factor (NGF), neurotrophin-3 (Ntf3), and neurotrophin-4/5 (Ntf5)
Using complementary molecular techniques, we demonstrated the conservation of the coding region of BDNF and neurotrophic tyrosine receptor kinase type 2 (Ntrk2) across several mammalian species, the mRNA expression of both genes within the uterus, and the uterine localization of both proteins in two species that menstruate, and four that do not
We have shown that several protein isoforms of each gene were present in the human uterus, and that the antibodies employed in this study were specific to BDNF and Ntrk2 respectively
Summary
Brain derived neurotrophic factor (BDNF) is one member of the neurotrophin family of secreted growth factors which comprises nerve growth factor (NGF), neurotrophin-3 (Ntf3), and neurotrophin-4/5 (Ntf). The neurotrophins are classically known for their participation in the development, growth, function, and survival of neurons in both the central and peripheral nervous system [1]. They induce a myriad of actions by signalling through the neurotrophic tyrosine receptor kinase family (Ntrk1 – formerly TrkA, Ntrk2 – formerly TrkB, Ntrk3 – formerly TrkC, and NGFR – formerly p75NTR). Studied in the nervous system, the interaction between BDNF and the full length Ntrk receptor has been shown to activate adhesion, angiogenesis, apoptosis, and proliferation pathways via the ras-mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and the phospholipase Cc1Ca2+ pathway [1,2,3]. In addition to participating in many physiological processes, the neurotrophins have been linked to numerous pathologies (Alzheimer’s, Parkinson’s, Huntington’s, cancer) and psychiatric disorders (bipolar, schizophrenia, depression) [1,4,5]
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