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Neurotransmitter receptors are involved in
transducing information in the central and peripheral nervous systems. My
laboratory studies receptors and their associated proteins and biochemical
signaling systems. We are especially interested in receptors that are
utilized for fast transmission, such as the nicotinic acetylcholine receptor.
Such receptors are composed of multiple subunits and the effects of each of
these subunits on the function and pharmacology of the assembled receptor is
incompletely understood.
The major project
underway in the laboratory involves neuronal nicotinic receptors. These
receptors are ligand-gated ion channels important in the brain in memory and
learning as well as mediating most of the neurotransmission in the peripheral
nervous system. Many subunits exist that can form these receptors and the
properties of the resulting receptors depend on their subunit composition.
Studies are underway to elucidate which combinations form in native tissues
(brain and peripheral ganglia) and by what mechanisms they regulate following
chronic exposure to nicotine (e.g. smoking). Several antibodies have been developed to
study these receptors, their subunit combinations, and their regulation both in vivo and in
vitro. Studies are underway trying to understand the
neurophysiological importance of subunit type and order in this pentameric
receptor. Using molecular approaches, receptors are being generated with
each of the five subunits being in a defined position to try to understand the
functional, pharmacological, and regulatory significance of each of the
subunits.
See Society for Neuroscience Abstract
Selected Publications:
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Mao D, Perry DC, Yasuda RP, Wolfe BB, Kellar KJ.:
The alpha4beta2alpha5 nicotinic cholinergic receptor in rat brain is
resistant to up-regulation by nicotine in vivo.
J Neurochem. 104:446-56, 2008
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Ortinski PI, Turner JR, Barberis A, Motamedi G, Yasuda
RP, Wolfe BB, Kellar KJ, Vicini S.:
Deletion of the GABA(A) receptor alpha1 subunit increases tonic GABA(A)
receptor current: a role for GABA uptake transporters.
J Neurosci. 26:9323, 2006
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Lu C, Fu Z, Karavanov I, Yasuda RP, Wolfe BB, Buonanno A,
Vicini S.:
NMDA receptor subtypes at autaptic synapses of cerebellar granule neurons.
J Neurophysiol. 96:2282-94, 2006
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Mao D, Yasuda RP, Fan H, Wolfe BB, Kellar KJ.:
Heterogeneity of nicotinic cholinergic receptors in rat superior cervical
and nodose Ganglia. Mol Pharmacol.
70:1693-9,
2006
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Marritt AM, Cox BC, Yasuda RP, McIntosh JM, Xiao Y, Wolfe
BB, Kellar KJ.:
Nicotinic cholinergic receptors in the rat retina: simple and mixed
heteromeric subtypes.
Mol Pharmacol. 68:1656-1668, 2005
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Brown KM, Wolfe BB, Wrathall JR.:
Rapid functional recovery after spinal cord injury in young rats.
J Neurotrauma. 22:559-574, 2005
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Brown KM, Wrathall JR, Yasuda RP, Wolfe BB.:
Glutamate receptor subunit expression after spinal cord injury in young
rats. Brain Res Dev Brain Res. 152:61-68, 2004
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Jarabek BR, Yasuda RP, Wolfe BB.:
Regulation of proteins affecting NMDA receptor-induced excitotoxicity in a
Huntington's mouse model. Brain 127: 505-516, 2004
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Carter TL, Rissman RA, Mishizen-Eberz AJ, Wolfe BB,
Hamilton RL, Gandy S, Armstrong DM.:
Differential preservation of AMPA receptor subunits in the hippocampi of
Alzheimer's disease patients according to Braak stage. Experimental Neurology, 187:299-309, 2004
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Mishizen-Eberz AJ, Rissman RA, Carter TL, Ikonomovic MD,
Wolfe BB, Armstrong DM.:
Biochemical and molecular studies of NMDA receptor subunits NR1/2A/2B in
hippocampal subregions throughout progression of Alzheimer's disease
pathology. Neurobiol Dis 15: 80-92, 2004
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Rissman RA, Mishizen-Eberz AJ, Carter TL, Wolfe BB, De
Blas AL, Miralles CP, Ikonomovic MD, Armstrong DM.:
Biochemical analysis of GABA(A) receptor subunits alpha 1, alpha 5, beta 1,
beta 2 in the hippocampus of patients with Alzheimer's disease
neuropathology. Neurosci 120:695-704,2003
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Al-Hallaq RA, Jarabek BR, Fu Z, Vicini S, Wolfe BB,
Yasuda RP.:
Association of NR3A with the N-methyl-D-aspartate receptor NR1 and NR2
subunits. Mol Pharmacol 62:1119-1127, 2002
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Brown KM, Wrathall JR, Yasuda RP, Wolfe BB.:
Quantitative measurement of glutamate receptor subunit protein expression in
the postnatal rat spinal cord. Dev Brain Res 137: 127-133, 2002
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Yeh J, Ferreira M, Ebert S, Yasuda RP, Kellar KJ, Wolfe
BB.:
Axotomy and nerve growth factor regulate levels of neuronal nicotinic
acetylcholine receptor alpha3 subunit protein in the rat superior cervical
ganglion. J Neurochem 79:258-265, 2001
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Al-Hallaq RA, Yasuda RP, Wolfe BB.:
Enrichment of N-methyl-D-aspartate NR1 splice variants and synaptic proteins
in rat postsynaptic densities. J Neurochem 77:110-119, 2001
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Yeh JJ, Yasuda RP, Dávila-García MI, Xiao Y, Ebert S,
Gupta T, Kellar KJ, Wolfe BB.:
Neuronal nicotinic acetylcholine receptor alpha3 subunit protein in rat
brain and sympathetic ganglion measured using a subunit-specific antibody:
regional and ontogenic expression. J Neurochem 77:336-346, 2001
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Adams MM, Smith TD, Moga D, Gallagher M, Wang Y, Wolfe
BB, Rapp PR, Morrison JH.:
Hippocampal dependent learning ability correlates with N-methyl-D-aspartate
(NMDA) receptor levels in CA3 neurons of young and aged rats. J Comp Neurol 432:230-243, 2001
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Prybylowski KL, Grossman SD, Wrathall JR, Wolfe BB.:
Expression of splice variants of the NR1 subunit of the N-methyl-D-aspartate
receptor in the normal and injured rat spinal cord. J Neurochem 76:797-805, 2001
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Prybylowski KL, Wolfe BB.:
Developmental differences in alternative splicing of the NR1 protein in rat
cortex and cerebellum. Dev Brain Res 123:143-150, 2000
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Wang Y, TesFaye E, Yasuda RP, Mash DC, Armstrong DM,
Wolfe BB.:
Effects of post-mortem delay on subunits of ionotropic glutamate receptors
in human brain. Mol Brain Res 80:123-131, 2000
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Prybylowski K, Rumbaugh G, Wolfe BB, Vicini S.:
Increased exon 5 expression alters extrasynaptic NMDA receptors in
cerebellar neurons. J Neurochem 75:1140-1146, 2000
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Grossman SD, Wolfe BB, Yasuda RP, Wrathall JR.:
Changes in NMDA receptor subunit expression in response to contusive spinal
cord injury. J Neurochem 75:174-184, 2000
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