Impact of seizures on developing dendrites: Implications for intellectual developmental disabilities

摘要

Childhood epilepsy can be severe and even catastrophic. In these instances, cognition can be impaired-leading to long-term intellectual disabilities. One factor that could potentially cause cognitive deficits is the frequent seizures that characterize intractable epilepsy. However, it has been difficult to separate the effects seizures may have from those of preexisting neuropathologies and/or the effects of ongoing anticonvulsant therapies. Therefore, important questions are: Do early life seizures produce the learning deficits? And if they do, how do they do it? Results from recent animal models studies reviewed here show that recurrent seizures in infancy stop the growth of CA1 hippocampal dendrites. We speculate that the molecular mechanisms responsible for seizure-induced growth suppression are homeostatic/ neuroprotective, used by the developing nervous system in an attempt to limit neuronal and network excitability and prevent the continued generation of seizures. However, by preventing the normal growth of dendrites, there is a reduction in CA1 glutamatergic synapses that supports long-lasting forms of synaptic plasticity thought to be the cellular basis of learning and memory. Therefore, dendrite growth suppression would reduce the neuroanatomic substrates for learning and memory, and in so doing could contribute in important ways to spatial learning and memory deficits that may be relevant to the cognitive deficits associated with childhood epilepsy.