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Baoji Xu Associate Professor of Pharmacology |
My laboratory is interested in elucidating the mechanism by which neurotrophins regulate the formation, maintenance, and function of neural circuits in the brain. Deficiencies in neurotrophins have been linked to neurodegenerative diseases, obesity, mental retardation, mood disorders, and other neurological disorders. Neurotrophins are a family of small and secreted growth factors, which include brain-derived neurotrophic factor (BDNF), nerve growth factor, neurotrophin-3, and neurotrophin-4/5. My laboratory uses a combination of mouse genetic, biochemical, molecular, histological, and behavioral approaches to identify the neural and molecular pathways mediating the diverse functions of neurotrophins. We have discovered that BDNF synthesized in dendrites controls activity-dependent modifications of dendritic spines, which are the postsynaptic sites for the vast majority of excitatory synapses. We have also found that neurotrophins are required for the formation and maintenance of the striatum. Their deficiencies likely contribute to selective degeneration of striatal neurons in Huntington's disease. Much of the current work in the laboratory focuses on the regulation of dendritic BDNF synthesis and its role in synaptic plasticity and learning, molecular mechanisms underlying the development and maintenance of the striatum and its relevance to Huntington's disease, molecular and neural substrates underlying the effect of BDNF on body weight, and development of therapeutic strategies for neurological disorders using BDNF or its mimetics.
Selected Publications:
Waterhouse EG, An JJ, Baydyuk M, Liao GY, Zheng K, Xu B.
BDNF promotes differentiation and maturation of adult-born neurons through GABA-ergic transmission
J Neurosci
32:14318, 2012
Liao GY, An JJ, Gharami K, Waterhouse EG, Vanevski F, Jones KR, Xu B.
Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin.
Nat Med.
18(4):564-71, 2012
Kaneko M, Xie Y, An JJ, Stryker MP, Xu B.
Dendritic BDNF synthesis is required for late-phase
spine maturation and recovery of cortical responses following sensory deprivation.
J Neurosci.
32(14):4790-802, 2012
Zheng K, An JJ, Yang F, Xu W, Xu ZQ, Wu
J, Hokfelt TG, Fisahn A, Xu B, Lu B.
TrkB signaling in parvalbumin-positive
interneurons is critical for gamma-band network
synchronization in hippocampus. Proc Natl Acad
Sci U S A. 108(41):17201-6, 2011
Baydyuk M, Russell T, Liao GY, Zang K, An JJ, Reichardt
LF, Xu B.
TrkB receptor controls striatal formation by regulating
the number of newborn striatal neurons.
Proc Natl Acad Sci U S A.
108:1669-74, 2011
Baydyuk M, Nguyen MT, Xu
B.
Chronic deprivation of TrkB signaling leads to selective
late-onset nigrostriatal dopaminergic degeneration.
Exp Neurol.
228:118-25, 2011
Xie Y, Hayden MR, Xu B.
BDNF Overexpression in the Forebrain Rescues
Huntington's Disease Phenotypes in YAC128 Mice.
J Neurosci.
30:14708-18, 2010
Lau AG, Irier HA, Gu J,
Tian D, Ku L, Liu G, Xia M, Fritsch B, Zheng JQ,
Dingledine R, Xu B, Lu B, Feng Y.
Distinct 3'UTRs
differentially regulate activity-dependent translation
of brain-derived neurotrophic factor (BDNF).
Proc Natl Acad Sci U S A.
107:15945-50, 2010
Fu X, Zang K, Zhou Z,
Reichardt LF, Xu B.
Retrograde neurotrophic
signaling requires a protein interacting with receptor
tyrosine kinases via C2H2 zinc fingers.
Mol Biol Cell.
21:36-49, 2010
Waterhouse EG, Xu B.:
New insights into the role of brain-derived neurotrophic
factor in synaptic plasticity.
Mol
Cell Neurosci., 2009
An JJ, Gharami K, Liao GY, Woo NH, Lau AG, Vanevski F,
Torre ER, Jones KR, Feng Y, Lu B, Xu B.:
Distinct role of long 3' UTR BDNF mRNA in spine
morphology and synaptic plasticity in hippocampal
neurons.
Cell. 134:175-87, 2008
Liao GY, Xu B.:
Cre recombinase-mediated gene deletion in layer 4 of
murine sensory cortical areas.
Genesis. 46:289-93, 2008
Gharami K, Xie Y, An JJ, Tonegawa S, Xu B.:
Brain-derived neurotrophic factor over-expression in the
forebrain ameliorates Huntington's disease phenotypes in
mice.
J Neurochem. 105:369-79, 2008
Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR,
Tecott LH, Reichardt LF.:
Brain-derived neurotrophic factor regulates energy
balance downstream of melanocortin-4 receptor.
Nat Neurosci. 6:736-42, 2003
Rico B, Xu B, Reichardt LF.:
TrkB receptor signaling is required for establishment of
GABAergic synapses in the cerebellum.
Nat Neurosci. 5:225-33, 2002
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Baoji Xu