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Neuroprotective effects of estradiol in the adult rat hippocampus: Interaction with insulin-like growth factor-I signalling

✍ Scribed by Iñigo Azcoitia; Amanda Sierra; Luis M. Garcia-Segura

Publisher
John Wiley and Sons
Year
1999
Tongue
English
Weight
251 KB
Volume
58
Category
Article
ISSN
0360-4012

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✦ Synopsis

We have previously shown that 17-␤-estradiol protects neurons in the dentate gyrus from kainic acidinduced death in vivo. To analyse whether this effect is mediated through estrogen receptors and through cross-talk between steroid and insulin-like growth factor (IGF) systems, we have concomitantly administered antagonists of estrogen receptor (ICI 182,780) or the IGF-I receptor (JB1) with estradiol. In addition, we have also administered IGF-I with or without the estrogen receptor antagonist. JB1 (20 µg/ml), ICI 182,780 (10 -7 M), and IGF-I (100 µg/ml) were delivered into the left lateral ventricle of young ovariectomized rats via an Alzet osmotic minipump (0.5 µl/hr) for 2 weeks. All rats received kainic acid (7 mg/Kg b.w.) or vehicle i.p. injections at day 7 after minipump implant. Also on day 7, rats treated i.c. v.with only ICI 182,780 or JB1 received a single i.p. injection of 17-␤-estradiol (150 µg/rat) or vehicle. On day 14 after minipump implant, the rats were killed, brains processed, and the number of surviving hilar neurons estimated by the optical disector technique. Both IGF-I and estradiol treatments resulted in over 90% survival of hilar neurons. The neuroprotective action of estradiol was blocked by ICI 182,780 and by JB1. Furthermore, IGF-I enhancement of neuronal survival was significantly reduced by ICI 182,780. These results indicate that in this model of hippocampal lesion, the neuroprotective effect of estradiol depends both on estrogen receptors and IGF-I receptors, while the protection exerted by IGF-I depends also on estrogen receptors. In conclusion, an interaction of estrogen receptor and IGF-I receptor signalling may mediate neuroprotection in the adult rat hippocampus.

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