title: Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer's Disease.
abstract: The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs) are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer's disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2) on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer's disease.
authors.affiliation: Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand. a.kwakowsky@auckland.ac.nz.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kwakowsky
authors.affiliation: School of Biomedical Sciences, Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research, The University of Queensland, Brisbane 4072, QLD, Australia. milnemichael834@gmail.com.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Milne
authors.affiliation: Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand. h.waldvogel@auckland.ac.nz.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Waldvogel
authors.affiliation: Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand. rlm.faull@auckland.ac.nz.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Faull
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D066187:Basal Forebrain / Q000378:metabolism*; D059329:Cholinergic Neurons / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000503:physiopathology*; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D004958:Estradiol
keywords: Alzheimer’s disease; basal forebrain cholinergic neurons 4; estradiol 1; neurotrophin receptors 3; neurotrophins 2