192-IMMUNOGLOBULIN G-SAPORIN PRODUCES GRADED BEHAVIORAL AND BIOCHEMICAL-CHANGES ACCOMPANYING THE LOSS OF CHOLINERGIC NEURONS OF THE BASAL FOREBRAIN AND CEREBELLAR PURKINJE-CELLS

被引:162
作者
WAITE, JJ
CHEN, AD
WARDLOW, ML
WILEY, RG
LAPPI, DA
THAL, LJ
机构
[1] UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093
[2] VET ADM MED CTR,DEPT NEUROL,SAN DIEGO,CA 92161
[3] DEPT VET AFFAIRS MED CTR,NEUROL SERV,NASHVILLE,TN 37212
[4] WHITTIER INST DIABET & ENDOCRINOL,DEPT MOLEC & CELLULAR GROWTH BIOL,LA JOLLA,CA 92037
关键词
D O I
10.1016/0306-4522(94)00479-O
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Immunolesions of the cholinergic basal forebrain were produced in rats using various intraventricular doses of the immunotoxin 192 immunoglobulin G-saporin: 0.34, 1.34, 2.0, 2.7 and 4.0 mu g/rat. A battery of behavioral tests, chosen on the basis of reported sensitivity to conventional medial septal or nucleus basalis lesions, was administered. Dose-dependent impairments were found in acquisition, spatial acuity and working memory in the water maze. Dose-dependent hyperactivity in the open field and in swimming speed was observed. The highest dose group (4.0 mu g) exhibited motoric disturbances which were particularly apparent in swimming and in clinging to an inclined screen. Response ana habituation to acoustic startle were diminished in the three higher dose groups. Histological results from acetylcholinesterase and low-affinity nerve growth factor receptor staining showed that the lesion was selective for cholinergic neurons bearing p75 nerve growth factor receptors in the basal forebrain nuclei. However, some Purkinje cells in the superficial layers of the cerebellum were also destroyed at the higher doses of immunotoxin. The activity of choline acetyltranferase, used as a marker of cholinergic deafferentation in regions innervated by the basal forebrain nuclei, was decreased with Increasing doses to a plateau level of about 90% (average depletion) for the two highest dose groups. These two groups were the only ones to exhibit consistent and severe behavioral impairments on all behavioral tests performed. Thus, for a relatively selective cholinergic basal forebrain lesion, almost a 90% reduction in choline acetyltransferase activity is needed to produce substantial behavioral deficits. It appears that either a considerable safety factor exists or robust compensatory mechanisms can ameliorate behavioral deficits from a major, but incomplete loss of cholinergic basal forebrain innervation.
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收藏
页码:463 / 476
页数:14
相关论文
共 40 条
[21]   SPATIAL-LEARNING IN RATS - CORRELATION WITH CORTICAL CHOLINE-ACETYLTRANSFERASE AND IMPROVEMENT WITH NGF FOLLOWING NBM DAMAGE [J].
MANDEL, RJ ;
GAGE, FH ;
THAL, LJ .
EXPERIMENTAL NEUROLOGY, 1989, 104 (03) :208-217
[22]  
MANDEL RJ, 1989, J PHARMACOL EXP THER, V251, P612
[23]   NUCLEUS BASALIS MAGNOCELLULARIS AND MEMORY - DIFFERENTIAL-EFFECTS OF 2 NEUROTOXINS [J].
MARKOWSKA, AL ;
WENK, GL ;
OLTON, DS .
BEHAVIORAL AND NEURAL BIOLOGY, 1990, 54 (01) :13-26
[24]   LEARNING-DEFICITS AFTER UNILATERAL AF64A LESIONS IN THE RAT BASAL FOREBRAIN - ROLE OF CHOLINERGIC AND NONCHOLINERGIC SYSTEMS [J].
NAKAMURA, S ;
TANI, Y ;
MAEZONO, Y ;
ISHIHARA, T ;
OHNO, T .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1992, 42 (01) :119-130
[25]   SPATIAL-LEARNING IMPAIRMENTS IN RATS WITH SELECTIVE IMMUNOLESION OF THE FOREBRAIN CHOLINERGIC SYSTEM [J].
NILSSON, OG ;
LEANZA, G ;
ROSENBLAD, C ;
LAPPI, DA ;
WILEY, RG ;
BJORKLUND, A .
NEUROREPORT, 1992, 3 (11) :1005-1008
[26]  
OVERSTREET DH, 1991, NEUROMETHODS, V19, P315
[27]   DISSOCIABLE EFFECTS ON SPATIAL MAZE AND PASSIVE-AVOIDANCE ACQUISITION AND RETENTION FOLLOWING AMPA-INDUCED AND IBOTENIC ACID-INDUCED EXCITOTOXIC LESIONS OF THE BASAL FOREBRAIN IN RATS - DIFFERENTIAL DEPENDENCE ON CHOLINERGIC NEURONAL LOSS [J].
PAGE, KJ ;
EVERITT, BJ ;
ROBBINS, TW ;
MARSTON, HM ;
WILKINSON, LS .
NEUROSCIENCE, 1991, 43 (2-3) :457-472
[28]  
Paxinos G., 1986, BRAIN NAVIGATOR, Vsecond
[29]   PURKINJE-CELLS OF ADULT-RAT CEREBELLUM EXPRESS NERVE GROWTH-FACTOR RECEPTOR IMMUNOREACTIVITY - LIGHT MICROSCOPIC OBSERVATIONS [J].
PIORO, EP ;
CUELLO, AC .
BRAIN RESEARCH, 1988, 455 (01) :182-186
[30]   COMPARATIVE EFFECTS OF QUISQUALIC AND IBOTENIC ACID-INDUCED LESIONS OF THE SUBSTANTIA INNOMINATA AND GLOBUS PALLIDUS ON THE ACQUISITION OF A CONDITIONAL VISUAL-DISCRIMINATION - DIFFERENTIAL-EFFECTS ON CHOLINERGIC MECHANISMS [J].
ROBBINS, TW ;
EVERITT, BJ ;
RYAN, CN ;
MARSTON, HM ;
JONES, GH ;
PAGE, KJ .
NEUROSCIENCE, 1989, 28 (02) :337-352