Effect of kainic acid treatment on insulin-like growth factor-2 receptors in the IGF2-deficient adult mouse brain

被引:13
作者
Dikkes, P.
Hawkes, C.
Kar, S.
Lopez, M. F.
机构
[1] Childrens Hosp, Dept Med, Boston, MA 02115 USA
[2] Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA
[3] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA 02115 USA
[5] McGill Univ, Dept Neurol & Neurosurg, Verdun, PQ H4H 1R3, Canada
[6] Univ Alberta, Dept Psychiat, Edmonton, AB T6G 2B7, Canada
关键词
hippocampus; insulin; insulin-like growth factor; kainic acid; receptor autoradiography;
D O I
10.1016/j.brainres.2006.11.022
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Insulin-like growth factor-2 (IGF2) is a member of the insulin gene family with known neurotrophic properties. The actions of IGF2 are mediated via the IGF type 1 and type 2 receptors as well as through the insulin receptors, all of which are widely expressed throughout the brain. Since IGF2 is up-regulated in the brain after injury, we wanted to determine whether the absence of IGF2 can lead to any alteration on brain morphology and/ or in the response of its receptor binding sites following a neurotoxic insult. No morphological differences were observed between the brains of IGF2 knockout (IGF2(-/-)) and wild-type control (IGF2'1') mice. However, our in vitro receptor autoradiography results indicate that IGF2(-/-) mice had lower endogenous levels of [I-125] IGF1 and [I-125] insulin receptor binding sites in the hippocampus and cerebellum as compared to IGF2(+/+) mice, while endogenous [I-125]IGF2 receptor binding showed a decrease only in the cerebellum. Seven days after kainic acid administration, the [I-125]insulin receptor binding sites were significantly decreased in all brain regions of the IGF2(+/+) mice, while the levels of [I-125]IGF1 and [I-125]IGF2 binding sites were decreased only in select brain areas. The IGF2(-/-) mice, on the other hand, showed increased [I-125]IGF1 and [I-125]IGF2 and [I-125]insulin receptor binding sites in selected regions such as the hippocampus and cerebellum. These results, taken together, suggest that deletion of IGF2 gene does not affect gross morphology of the brain but does selectively alter endogenous [I-125]IGF1, [I-125]IGF2 and [I-125] insulin receptor binding sites and their response to neurotoxicity. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:77 / 87
页数:11
相关论文
共 64 条
[1]   INSULIN AND INSULIN-LIKE GROWTH-FACTOR RECEPTORS IN THE NERVOUS-SYSTEM [J].
ADAMO, M ;
RAIZADA, MK ;
LEROITH, D .
MOLECULAR NEUROBIOLOGY, 1989, 3 (1-2) :71-100
[2]   BRAIN NEURONS DEVELOP IN A SERUM AND GLIAL FREE ENVIRONMENT - EFFECTS OF TRANSFERRIN, INSULIN, INSULIN-LIKE GROWTH FACTOR-I AND THYROID-HORMONE ON NEURONAL SURVIVAL, GROWTH AND DIFFERENTIATION [J].
AIZENMAN, Y ;
DEVELLIS, J .
BRAIN RESEARCH, 1987, 406 (1-2) :32-42
[3]   INSULIN AND INSULIN-LIKE GROWTH-FACTORS IN THE CNS [J].
BASKIN, DG ;
WILCOX, BJ ;
FIGLEWICZ, DP ;
DORSA, DM .
TRENDS IN NEUROSCIENCES, 1988, 11 (03) :107-111
[4]   INSULIN-LIKE GROWTH FACTOR-II IS INDUCED DURING WOUND REPAIR FOLLOWING HYPOXIC-ISCHEMIC INJURY IN THE DEVELOPING RAT-BRAIN [J].
BEILHARZ, EJ ;
BASSETT, NS ;
SIRIMANNE, ES ;
WILLIAMS, CE ;
GLUCKMAN, PD .
MOLECULAR BRAIN RESEARCH, 1995, 29 (01) :81-91
[6]   ELECTROGRAPHIC, CLINICAL AND PATHOLOGICAL ALTERATIONS FOLLOWING SYSTEMIC ADMINISTRATION OF KAINIC ACID, BICUCULLINE OR PENTETRAZOLE - METABOLIC MAPPING USING THE DEOXYGLUCOSE METHOD WITH SPECIAL REFERENCE TO THE PATHOLOGY OF EPILEPSY [J].
BENARI, Y ;
TREMBLAY, E ;
RICHE, D ;
GHILINI, G ;
NAQUET, R .
NEUROSCIENCE, 1981, 6 (07) :1361-1391
[7]   SPECIFIC ASSAY FOR INSULIN-LIKE GROWTH-FACTOR (IGF)-II USING THE IGF BINDING-PROTEINS EXTRACTED FROM HUMAN CEREBROSPINAL-FLUID [J].
BINOUX, M ;
LASSARRE, C ;
GOURMELEN, M .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1986, 63 (05) :1151-1155
[8]   LOCALIZATION OF BINDING-SITES FOR INSULIN-LIKE GROWTH FACTOR-I (IGF-I) IN THE RAT-BRAIN BY QUANTITATIVE AUTORADIOGRAPHY [J].
BOHANNON, NJ ;
CORP, ES ;
WILCOX, BJ ;
FIGLEWICZ, DP ;
DORSA, DM ;
BASKIN, DG .
BRAIN RESEARCH, 1988, 444 (02) :205-213
[9]  
Breese CR, 1996, J COMP NEUROL, V369, P388
[10]   INSULIN-LIKE GROWTH FACTOR-I INCREASES BRAIN GROWTH AND CENTRAL-NERVOUS-SYSTEM MYELINATION IN TRANSGENIC MICE [J].
CARSON, MJ ;
BEHRINGER, RR ;
BRINSTER, RL ;
MCMORRIS, FA .
NEURON, 1993, 10 (04) :729-740