DOPAMINERGIC GRAFTS IMPLANTED INTO THE NEONATAL OR ADULT STRIATUM - COMPARATIVE EFFECTS ON ROTATION AND PAW REACHING DEFICITS INDUCED BY SUBSEQUENT UNILATERAL NIGROSTRIATAL LESIONS IN ADULTHOOD

被引:41
作者
ABROUS, DN [1 ]
TORRES, EM [1 ]
DUNNETT, SB [1 ]
机构
[1] UNIV CAMBRIDGE, DEPT EXPTL PSYCHOL, CAMBRIDGE, ENGLAND
关键词
D O I
10.1016/0306-4522(93)90237-A
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We have examined whether dopaminergic mesencephalic grafts implanted into neonates can provide more extensive protection against deficits induced by a subsequent unilateral lesion of the mesotelencephalic dopaminergic pathway than when the grafts are implanted in adulthood. A dopamine-rich neuronal cell suspension obtained from embryonic day 14 mesencephali was injected unilaterally into the neostriatum of otherwise intact neonatal or adult rats at one day or two months of age, respectively. Two months later, the ipsilateral mesotelencephalic dopaminergic pathway was destroyed by unilateral injection of 6-hydroxydopamine. The behavioural effects of the grafts were evaluated in tests of drug-induced rotation and skilled paw reaching. After completion of the behavioural testing, animals were killed and brains were processed for tyrosine hydroxylase immunohistochemistry. In rats receiving transplants as adults, grafts were compact and located in the neostriatum. In contrast, in rats receiving transplants neonatally, fewer dopaminergic neurons survived and they were dispersed over a large area of the host neostriatum and nucleus accumbens. After lesioning, all animals manifested strong rotation in response to amphetamine: this was not initially prevented by the grafts, made at either age, up to three months following the lesion, but was reduced in both groups of grafted rats by seven months after lesioning. This prolonged period for the development of recovery contrasts markedly with the rapid recovery obtained when similar grafts are implanted into the denervated neostriatum of adult rats that had received a prior 6-hydroxydopamine lesion. The development of apomorphine rotation, thought to reflect the development of receptor supersensitivity following lesions, was partially blocked to a similar extent by the grafts in both age groups. In contrast to their effects in the rotation tests, the dopaminergic grafts had no detectable effect on the profound contralateral deficit induced by the lesions in the paw-reaching test, whether implanted into neonatal or adult brains. Thus, whereas the age of the host at the time of implantation can markedly influence the gross morphological organization of dopaminergic grafts implanted into the neostriatum, the functional effects were similar, whether the grafts were implanted into neonatal or adult hosts.
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页码:657 / 668
页数:12
相关论文
共 69 条
[1]   ESTIMATION OF NUCLEAR POPULATION FROM MICROTOME SECTIONS [J].
ABERCROMBIE, M .
ANATOMICAL RECORD, 1946, 94 (02) :239-247
[2]  
ABOUS DN, 1992, NEUROSCIENCE, V53, P157
[3]   INTRAACCUMBENS IMPLANTS OF EMBRYONIC DOPAMINERGIC-NEURONS REVERSE THE BEHAVIORAL SUPERSENSITIVITY TO OPIATES EVOKED BY LESION OF THE MESOLIMBIC DOPAMINERGIC PATHWAY [J].
ABROUS, DN ;
STINUS, L ;
LEMOAL, M ;
HERMAN, JP .
BRAIN RESEARCH, 1990, 525 (01) :155-159
[4]  
ABROUS DN, 1992, EXP BRAIN RES, V91, P181
[5]   EFFECTS OF INTRACEREBRAL DOPAMINERGIC GRAFTS ON BEHAVIORAL DEFICITS INDUCED BY NEONATAL 6-HYDROXYDOPAMINE LESIONS OF THE MESOTELENCEPHALIC DOPAMINERGIC PATHWAY [J].
ABROUS, DN ;
CHOULLI, K ;
ROUGEPONT, F ;
SIMON, H ;
LEMOAL, M ;
HERMAN, JP .
NEUROSCIENCE, 1993, 54 (02) :499-511
[6]   DEVELOPMENT OF INTRACEREBRAL DOPAMINERGIC GRAFTS - A COMBINED IMMUNOHISTOCHEMICAL AND AUTORADIOGRAPHIC STUDY OF ITS TIME COURSE AND ENVIRONMENTAL-INFLUENCES [J].
ABROUS, N ;
GUY, J ;
VIGNY, A ;
CALAS, A ;
LEMOAL, M ;
HERMAN, JP .
JOURNAL OF COMPARATIVE NEUROLOGY, 1988, 273 (01) :26-41
[7]  
ANNETT LE, 1990, PROG BRAIN RES, V82, P535
[8]   RE-INNERVATION OF THE DENERVATED STRIATUM BY SUBSTANTIA NIGRA TRANSPLANTS - FUNCTIONAL CONSEQUENCES AS REVEALED BY PHARMACOLOGICAL AND SENSORIMOTOR TESTING [J].
BJORKLUND, A ;
DUNNETT, SB ;
STENEVI, U ;
LEWIS, ME ;
IVERSEN, SD .
BRAIN RESEARCH, 1980, 199 (02) :307-333
[9]   MECHANISMS OF ACTION OF INTRACEREBRAL NEURAL IMPLANTS - STUDIES ON NIGRAL AND STRIATAL GRAFTS TO THE LESIONED STRIATUM [J].
BJORKLUND, A ;
LINDVALL, O ;
ISACSON, O ;
BRUNDIN, P ;
WICTORIN, K ;
STRECKER, RE ;
CLARKE, DJ ;
DUNNETT, SB .
TRENDS IN NEUROSCIENCES, 1987, 10 (12) :509-516
[10]  
BJORKLUND A, 1983, ACTA PHYSIOL SCAND, P9