Bilateral fetal striatal grafts in the 3-nitropropionic acid-induced hypoactive model of Huntington's disease

被引:27
作者
Borlongan, CV
Koutouzis, TK
Poulos, SG
Saporta, S
Sanberg, PR
机构
[1] Univ S Florida, Coll Med, Div Neurol Surg, Tampa, FL 33612 USA
[2] Univ S Florida, Coll Med, Program Neurosci, Dept Surg, Tampa, FL 33612 USA
[3] Univ S Florida, Coll Med, Program Neurosci, Dept Neurol, Tampa, FL 33612 USA
[4] Univ S Florida, Coll Med, Program Neurosci, Dept Psychiat, Tampa, FL 33612 USA
[5] Univ S Florida, Coll Med, Program Neurosci, Dept Psychol, Tampa, FL 33612 USA
[6] Univ S Florida, Coll Med, Program Neurosci, Dept Pharmacol, Tampa, FL 33612 USA
[7] Univ S Florida, Coll Med, Dept Anat, Tampa, FL 33612 USA
关键词
3-nitropropionic acid; Huntington's disease; neural transplantation; locomotor activity; rat model;
D O I
10.1016/S0963-6897(97)00170-X
中图分类号
Q813 [细胞工程];
学科分类号
摘要
We investigated the 3-nitropropionic acid (3-NP)-induced hypoactive model of Huntington's disease (HD) to demonstrate whether fetal tissue transplantation can ameliorate behavioral deficits associated with a more advanced stage of HD, Twelve-week-old Sprague-Dawley rats were introduced to the 3-NP dosing regimen (10 mg/kg, i.p., once every 4 days for 28 consecutive days), and were then tested for general spontaneous locomotor activity in the Digiscan locomotor apparatus, All rats displayed significant hypoactivity compared to their pre-3-NP injection locomotor activity, Randomly selected rats then received bilateral intrastriatal solid grafts of fetal striatal (lateral ganglionic eminence, LGE) tissues from embryonic day 14 rat fetuses, Approximately 1/3 of each LGE in hibernation medium was infused into each lesioned host striatum, In control rats, medium alone mas infused intrastriatally. A 3-mo posttransplant maturation period was allowed prior to locomotor activity testing. Animals receiving fetal LGE grafts exhibited a significant increase in locomotor activity compared to their post-3-NP injection activity or to the controls' posttransplant activity, Surviving striatal grafts mere noted in functionally recovered animals, This observation supports the use of fetal striatal transplants to correct the akinetic stage of HD, To the best of our knowledge, this is the first study that has investigated the effects of fetal striatal transplantation in a hypoactive model of HD, (C) 1998 Elsevier Science Inc.
引用
收藏
页码:131 / 135
页数:5
相关论文
共 20 条
[1]  
BEAL MF, 1993, J NEUROSCI, V13, P4181
[2]   SYSTEMIC 3-NITROPROPIONIC ACID - BEHAVIORAL DEFICITS AND STRIATAL DAMAGE IN ADULT-RATS [J].
BORLONGAN, CV ;
KOUTOUZIS, TK ;
RANDALL, TS ;
FREEMAN, TB ;
CAHILL, DW ;
SANBERG, PR .
BRAIN RESEARCH BULLETIN, 1995, 36 (06) :549-556
[3]  
Borlongan CV, 1996, NEURODEGENERATION, V5, P189
[4]   BEHAVIORAL PATHOLOGY INDUCED BY REPEATED SYSTEMIC INJECTIONS OF 3-NITROPROPIONIC ACID MIMICS THE MOTORIC SYMPTOMS OF HUNTINGTONS-DISEASE [J].
BORLONGAN, CV ;
KOUTOUZIS, TK ;
FREEMAN, TB ;
CAHILL, DW ;
SANBERG, PR .
BRAIN RESEARCH, 1995, 697 (1-2) :254-257
[5]   AGE-DEPENDENT VULNERABILITY OF THE STRIATUM TO THE MITOCHONDRIAL TOXIN 3-NITROPROPIONIC ACID [J].
BROUILLET, E ;
JENKINS, BG ;
HYMAN, BT ;
FERRANTE, RJ ;
KOWALL, NW ;
SRIVASTAVA, R ;
ROY, DS ;
ROSEN, BR ;
BEAL, MF .
JOURNAL OF NEUROCHEMISTRY, 1993, 60 (01) :356-359
[6]   Paucity of P-zones in striatal grafts prohibit commencement of clinical trials in Huntington's disease [J].
Brundin, P ;
Fricker, RA ;
Nakao, N .
NEUROSCIENCE, 1996, 71 (03) :895-897
[7]  
Bruyn G., 1968, HDB CLINICAL NEUROLO, V6, P298
[8]   DEVELOPMENT OF THE HUMAN STRIATUM - IMPLICATIONS FOR FETAL STRIATAL TRANSPLANTATION IN THE TREATMENT OF HUNTINGTONS-DISEASE [J].
FREEMAN, TB ;
SANBERG, PR ;
ISACSON, O .
CELL TRANSPLANTATION, 1995, 4 (06) :539-545
[9]  
Fricker R. A., 1994, Society for Neuroscience Abstracts, V20, P473
[10]   SYSTEMIC 3-NITROPROPIONIC ACID - LONG-TERM EFFECTS ON LOCOMOTOR BEHAVIOR [J].
KOUTOUZIS, TK ;
BORLONGAN, CV ;
SCORCIA, T ;
CREESE, I ;
CAHILL, DW ;
FREEMAN, TB ;
SANBERG, PR .
BRAIN RESEARCH, 1994, 646 (02) :242-246