The new neurons generated as a result of neural damage due to epilepsy show a reduced excitability that could alleviate the disorder, researchers have found. The researchers said their results suggest that therapies for epilepsy aimed at inducing neurogenesis could prove effective in alleviating the disorder.
In an article in the December 21, 2006, issue of the journal Neuron, published by Cell Press, Olle Lindvall and colleagues at Lund University Hospital and Stem Cell Center described studies in rats examining neurons generated after an epileptic event has been triggered in the animals.
In their experiments, the researchers compared the properties of new neurons generated in rats allowed to exercise by running on a wheel with those in rats in which epileptic seizures were induced by electrical brain stimulation. Specifically, the researchers analyzed the electrical properties of a type of new cells, called granule cells, in the structure called the dentate gyrus of the hippocampus. This structure is known to be a "gate" for propagation of seizures in the hippocampus, a center for learning and memory.
The scientists’ analysis showed that the new neurons in both the runners and the epileptic animals had all the characteristics of mature dentate gyrus cells. However, they found that neurons born into an epileptic environment, compared to the physiological running environment, showed reduced excitatory connectivity to other neurons, as well as increased inhibitory connectivity. Such differences could mean the newly generated neurons "could have significant beneficial effect on the epileptic syndrome," concluded the researchers.
"Our study demonstrates that both a physiological stimulus and an insult to the adult brain trigger the formation of new dentate granule cells, which are functionally integrated into hippocampal neural circuitry," concluded Lindvall and colleagues. They wrote that "following insult, the functional connectivity of new neurons seems to develop in order to mitigate the dysfunction in the epileptic brain. These data provide further evidence for a therapeutic potential of endogenous neurogenesis."
The researchers include Katherine Jakubs, Avtandil Nanobashvili, Sara Bonde, Christine T. Ekdahl, Zaal Kokaia, Merab Kokaia, and Olle Lindvall of Lund University Hospital and Stem Cell Center in Lund, Sweden.
This work was supported by Swedish Research Council, EU project LSHBCT-2003-503005 (EUROSTEMCELL), and Söderberg, Crafoord, and Kock Foundations. Lund Stem Cell Center is supported by a Center of Excellence grant in Life Sciences from Swedish Foundation for Strategic Research.
Jakubs et al.: "Environment Matters: Synaptic Properties of Neurons Born in the Epileptic Adult Brain Develop to Reduce Excitability." Publishing in Neuron 52, 1047–1059, December 21, 2006 DOI 10.1016/j.neuron.2006.11.004. www.neuron.org
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