MK-801 upregulates NR2A protein levels and induces functional recovery of the lpsilateral hemidiaphragm following acute C2 hemisection in adult rats

被引:26
作者
Alilain, Warren J.
Goshgarian, Harry G.
机构
[1] Wayne State Univ, Sch Med, Dept Psychiat & Biobehav Sci, Cellular & Clin Neurobiol Program, Detroit, MI USA
[2] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Cellular & Clin Neurobiol Program, Detroit, MI USA
关键词
C2; hemisection; spinal cord injuries; motor recovery; phrenic nucleus; plasticity; long-term potentiation; N-methyl-D-aspartate (NMDA); MK-801; NMDA-receptor antagonist;
D O I
10.1080/10790268.2007.11753950
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: C2 hemisection results in paralysis of the ipsilateral hemidiaphragm. Recent data indicate that an upregulation of the N-methyl-D-aspartate (NMDA) receptor 2A subunit following chronic C2 hemisection is associated with spontaneous hemidiaphragmatic recovery following injury. MK-801, an antagonist of the NMDA receptor, upregulates the NR2A subunit in neonatal rats. Hypothesis: We hypothesized that administration of MK-801 to adult, acute C2-hemisected rats would result in an increase of NR2A in the spinal cord. Furthermore, we hypothesized that upregulation of NR2A would be associated with recovery of the ipsilateral hemidiaphragm as in the chronic studies. Design: To develop a dose-response curve, adult rats were treated with varying doses of MK-801 and their spinal cords harvested and assessed for NR2A as well as AMPA GluR1 and GluR2 subunit protein levels. In the second part of this study, C2-hemisected animals received MK-801. Following treatment, the animals were assessed for recovery of the hemidiaphragm through electromyographic recordings and their spinal cords assessed for NR2A, GluRl, and GluR2. Results: Treatment with MK-801 leads to an increase of the NR2A subunit in the spinal cords of adult noninjured rats. There were no changes in the expression of GluR1 and GluR2 in these animals. Administration of MK-801 to C2-hemisected rats resulted in recovery of the ipsilateral hemidiaphragm, an increase of NR2A, and a decrease of GluR2. Conclusion: Our findings strengthen the evidence that the NR2A subunit plays a substantial role in mediating recovery of the paralyzed hemidiaphragm following C2 spinal cord hemisection.
引用
收藏
页码:346 / 354
页数:9
相关论文
共 53 条
[1]  
ALILAIN WJ, 2005, SOC NEROSC ANN M WAS
[2]  
ALILAIN WJ, 2005, J SPINAL CORD MED, V28, P366
[3]   Pegylated brain-derived neurotrophic factor shows improved distribution into the spinal cord and stimulates locomotor activity and morphological changes after injury [J].
Ankeny, DP ;
McTigue, DM ;
Guan, Z ;
Yan, Q ;
Kinstler, O ;
Stokes, BT ;
Jakeman, LB .
EXPERIMENTAL NEUROLOGY, 2001, 170 (01) :85-100
[4]   BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia [J].
Baker-Herman, TL ;
Fuller, DD ;
Bavis, RW ;
Zabka, AG ;
Golder, FJ ;
Doperalski, NJ ;
Johnson, RA ;
Watters, JJ ;
Mitchell, GS .
NATURE NEUROSCIENCE, 2004, 7 (01) :48-55
[5]  
Bennett MVL, 1996, COLD SPRING HARB SYM, V61, P373
[6]   Neurotrophic factors increase axonal growth after spinal cord injury and transplantation in the adult rat [J].
Bregman, BS ;
McAtee, M ;
Dal, HN ;
Kuhn, PL .
EXPERIMENTAL NEUROLOGY, 1997, 148 (02) :475-494
[7]   Enhancement of long-term potentiation at CA1-subiculum synapses in MK-801-treated rats [J].
Buck, N ;
Cali, S ;
Behr, J .
NEUROSCIENCE LETTERS, 2006, 392 (1-2) :5-9
[8]   DIFFERENTIAL-EFFECTS OF MK-801 ON BRAIN-DERIVED NEUROTROPHIC FACTOR MESSENGER-RNA LEVELS IN DIFFERENT REGIONS OF THE RAT-BRAIN [J].
CASTREN, E ;
BERZAGHI, MD ;
LINDHOLM, D ;
THOENEN, H .
EXPERIMENTAL NEUROLOGY, 1993, 122 (02) :244-252
[9]   Synaptic innervation density is regulated by neuron-derived BDNF [J].
Causing, CG ;
Gloster, A ;
Aloyz, R ;
Bamji, SX ;
Chang, E ;
Fawcett, J ;
Kuchel, G ;
Miller, FD .
NEURON, 1997, 18 (02) :257-267
[10]   BRAIN-STEM NETWORK CONTROLLING DESCENDING DRIVE TO PHRENIC MOTONEURONS IN RAT [J].
DOBBINS, EG ;
FELDMAN, JL .
JOURNAL OF COMPARATIVE NEUROLOGY, 1994, 347 (01) :64-86