IGF2 knockout mice are resistant to kainic acid-induced seizures and neurodegeneration.
Insulin-like growth factor 2 (Igf2), a member of the insulin gene family, is important for brain development and has known neurotrophic properties. Though Igf2, its receptors, and binding proteins, are expressed in the adult CNS, their role in the adult brain is less well-understood. Here we studied how Igf2 deficiency affects brains of adult Igf2 knockout (Igf2(-/-)) mice following neurotoxic insult produced by the glutamate analog kainic acid (KA). Igf2(-/-) mice exhibited attenuated epileptiform activity in response to KA and were less susceptible to hippocampal neurodegeneration compared with Igf2(+/+) mice. Other brain areas protected by the lack of Igf2 included the amygdala complex, septal nuclei, and thalamic region. Apoptosis, as determined by TUNEL and Hoechst 33342 staining, was accordingly less for Igf2(-/-) mice. Hippocampal slices from Igf2(-/-) mice also were protected against the effects epileptogenic effects of KA compared to Igf2(+/+) mice suggesting that neuroprotection afforded by a lack of Igf2 may be developmental in origin and experiments demonstrating enhanced synaptic inhibition in slices taken from Igf2(-/-) mice support this hypothesis. Taken together, these results suggest that Igf2 may be important for mechanisms and circuits that contribute to neurodegeneration and epilepsy.
Dikkes
Pieter
P
Children's Hospital/Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
B Jaffe
David
D
Guo
Wei-Hui
WH
Chao
Christina
C
Hemond
Peter
P
Yoon
Kihoon
K
Zurakowski
David
D
Lopez
Mary Frances
MF
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007608:Kainic Acid / Q000633:toxicity; D008032:Limbic System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009498:Neurotoxins / Q000633:toxicity; D009924:Organ Culture Techniques
C513121:IGF2 protein, mouse; D009498:Neurotoxins; D007335:Insulin-Like Growth Factor II; D007608:Kainic Acid