INTERACTIONS BETWEEN MPTP-INDUCED AND AGE-RELATED NEURONAL DEATH IN A MURINE MODEL OF PARKINSONS-DISEASE

被引:14
作者
TATTON, WG
GREENWOOD, CE
SENIUK, NA
SALO, PT
机构
[1] UNIV TORONTO,DEPT PSYCHIAT,TORONTO M5S 1A8,ONTARIO,CANADA
[2] UNIV TORONTO,DEPT NUTR SCI,TORONTO M5S 1A8,ONTARIO,CANADA
关键词
D O I
10.1017/S0317167100041494
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Abiotrophy is hypothesized to explain the onset and time course of deficits in Parkinson's disease (PD) Abiotrophy includes: 1) exposure to agent(s) causing the death of dopaminergic nigrostriatal neurons (DNSns), 2) gradual death of DNSns with age, 3) summation of 1) and 2) until DNSn numbers fall below a threshold for detectable neurological deficits. Murine DNSn death following methyl-phenyl-tetrahydropyridine (MPTP) exposure occurs according to an exponential relationship while age-related death of DNSns occurs according to a second exponential relationship. Summing the two exponential losses overestimates experimental DNSn death showing a simple abiotrophic model is not sufficient. Aged murine DNSns greatly increase their dopamine synthesis and the density of their striatal axon terminals which may explain the above threshold. Murine DNSns die gradually after MPTP exposure and L-deprenyl treatment rescues MPTP-damaged DNSns by a previously undiscovered action, altering the abiotrophic interactions and possibly explaining the slowed progression of PD found with deprenyl treatment.
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页码:124 / 133
页数:10
相关论文
共 77 条
[1]   MICROGLIAL RESPONSE TO 6-HYDROXYDOPAMINE-INDUCED SUBSTANTIA NIGRA LESIONS [J].
AKIYAMA, H ;
MCGEER, PL .
BRAIN RESEARCH, 1989, 489 (02) :247-253
[2]   USE OF TISSUE-CULTURE MODELS TO STUDY NEURONAL REGULATORY TROPHIC AND TOXIC FACTORS IN THE AGED BRAIN [J].
AZMITIA, EC ;
WHITAKERAZMITIA, PM ;
BARTUS, R .
NEUROBIOLOGY OF AGING, 1988, 9 (5-6) :743-758
[3]   CYTOLOGICAL AND CYTOCHEMICAL (RNA) STUDIES ON RUBRAL NEURONS AFTER UNILATERAL RUBROSPINAL TRACTOTOMY - THE IMPACT OF GM1 GANGLIOSIDE ADMINISTRATION [J].
BARRON, KD ;
BANERJEE, M ;
DENTINGER, MP ;
SCHEIBLY, ME ;
MANKES, R .
JOURNAL OF NEUROSCIENCE RESEARCH, 1989, 22 (03) :331-337
[4]  
BARRON KV, 1986, NERVE ORGAN TISSUE R, P3
[5]  
BERNHEIMER H, 1973, J NEUROL SCI, V20, P415, DOI 10.1016/0022-510X(73)90175-5
[6]   POTENTIATION OF ANTI AKINETIC EFFECT AFTER L-DOPA TREATMENT BY AN INHIBITOR OF MAO-B, DEPRENIL [J].
BIRKMAYER, W ;
RIEDERER, P ;
YOUDIM, MBH ;
LINAUER, W .
JOURNAL OF NEURAL TRANSMISSION, 1975, 36 (3-4) :303-326
[7]   ASTROCYTES AS A PRIMARY LOCUS FOR THE CONVERSION MPTP INTO MPP [J].
BROOKS, WJ ;
JARVIS, MF ;
WAGNER, GC .
JOURNAL OF NEURAL TRANSMISSION, 1989, 76 (01) :1-12
[8]   A PRIMATE MODEL OF PARKINSONISM - SELECTIVE DESTRUCTION OF DOPAMINERGIC-NEURONS IN THE PARS COMPACTA OF THE SUBSTANTIA NIGRA BY N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE [J].
BURNS, RS ;
CHIUEH, CC ;
MARKEY, SP ;
EBERT, MH ;
JACOBOWITZ, DM ;
KOPIN, IJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (14) :4546-4550
[9]   ETIOLOGY OF PARKINSONS-DISEASE [J].
CALNE, DB ;
LANGSTON, JW .
LANCET, 1983, 2 (8365) :1457-1459
[10]   PRIMATE MODEL OF PARKINSONISM - SELECTIVE LESION OF NIGROSTRIATAL NEURONS BY 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE PRODUCES AN EXTRAPYRAMIDAL SYNDROME IN RHESUS-MONKEYS [J].
CHIUEH, CC ;
BURNS, RS ;
MARKEY, SP ;
JACOBOWITZ, DM ;
KOPIN, IJ .
LIFE SCIENCES, 1985, 36 (03) :213-218