Methamphetamine-induced Loss Of Striatal Dopamine Innervation In Bdnf Heterozygote Mice Does Not Further Reduce D-3 Receptor Concentrations
1-methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine mptp; behavioral; caudate putamen; differential regulation; dopamine; haloperidol treatment; monkey; motor neurons; mutant mice; Neurosciences & Neurology; neurotrophic factor; nucleus accumbens; parkinsons-disease; parkinsons-disease; sensitization; Striatum; substantia-nigra; transporter; tyrosine hydroxylase
Depletion of dopamine (DA) reduces D, receptor number, but D-3 receptor expression is also regulated by brain-derived neurotrophic factor (BDNF). We took advantage of transgenic heterozygous BDNF mutant mice (+/-) to determine if reduced BDNF and loss of DA fibers produced by methamphetamine were additive in their impact on D-3 receptor number. We assessed selective markers of the dopaminergic system including caudate-putamen DA concentrations and quantitative autoradiographic measurement of tyrosine hydroxylase (TH) levels, DA transporter (DAT), and DA D-3 receptor binding between vehicle and methamphetamine-treated BDNF +/- and their wildtype (WT) littermate control mice. Caudate-putamen DA concentrations, TH and DAT levels were significantly reduced following methamphetamine treatment in both WT and BDNF +/- mice. The extent of methamphetamine-induced reduction in TH and DAT was greater for the WT than BDNF +/- mice and DAT levels were also decreased to a greater extent in nucleus accumbens of WT as compared to BDNF +/- mice. Lower D-3 receptor existed in caudate-putamen and nucleus accumbens in BDNF +/- mice and these differences were not affected by methamphetamine treatment. Taken together, these results not only substantiate the importance of BDNF in controlling D-3 receptor expression, but also indicate that a methamphetamine-induced depletion of DA fibers fails to produce an additive effect with lowered BDNF for control of D-3 receptor expression. In addition, the reduction of D-3 receptor expression is associated with a decreased neurotoxic response to methamphetamine in BDNF +/- mice. (C) 2004 Wiley-Liss, Inc.
Joyce J N; Renish L; Osredkar T; Walro J M; Kucera J; Dluzen D E
Synapse
2004
2004-04
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/syn.10309" target="_blank" rel="noreferrer noopener">10.1002/syn.10309</a>
Rat Alpha(1)-macroglobulin Enhances Nerve Growth Factor-promoted Neurite Outgrowth, Trka Phosphorylation, And Gene Expression Of Pheochromocytoma Pc12 Cells
alpha-2-macroglobulin receptor; alpha-macroglobulins; alpha(2)-macroglobulin; Biochemistry & Molecular Biology; caudate putamen; cerebral cortical-neurons; choline-acetyltransferase; delayed-response genes; immediate-early genes; myelin-associated glycoprotein; nerve growth factor receptor; neurite-promoting factor; Neurosciences & Neurology; ngf receptor; protein; signal; signal-transduction; transduction
Monoamine-activated human alpha(2)-macroglobulin (alpha(2)M) has been previously demonstrated to inhibit TrkA-, TrkB-, and TrkC-mediated signal transduction. Rat alpha(1),-macroglobulin (alpha(1)M) and alpha(2)M are structural homologues of human alpha(2)M, but rat alpha(1)M is distinctly different from rat alpha(2)M in many ways and its role in the mammalian nervous system is unknown. In this report, monoamine-activated rat alpha(1)M was demonstrated to enhance in a dose-dependent manner nerve growth factor (NGF)-promoted neurite outgrowth in pheochromocytoma PC12 cells. Monoamine-activated alpha(1)M by itself, however, was neither neurotrophic nor mitogenic to PC12 cells. To investigate further its possible mode of action, the ability of monoamine-activated alpha(1)M and normal alpha(1)M to bind and to activate the NGF receptor (TrkA) was investigated. Monoamine-activated alpha(1)M formed a more stable complex with TrkA than normal alpha(1)M, but the binding of mono-amina-activated alpha(1)M to TrkA was adversely affected by prior stimulation of TrkA with NGF. In addition, monoamine-activated alpha(1)M enhanced the NGF-promoted TrkA phosphorylation and up-regulated the expression of NGF-inducible immediate-early genes (c-jun and NGFI-A) and delayed-response genes (SCG10 and transin) in PC12 cells; normal alpha(1)M, in contrast, produced little or no effect, This study demonstrates that alpha(1)M, the constitutive form of ar-macroglobulin in the rat, possesses the ability to promote NGF-mediated differentiation in PC12 cells, possibly via its direct action on TrkA receptors and TrkA-mediated signal transduction and gene expression.
Lee P G; Koo P H
Journal of Neurochemistry
2000
2000-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1046/j.1471-4159.2000.0740081.x" target="_blank" rel="noreferrer noopener">10.1046/j.1471-4159.2000.0740081.x</a>