Could hippocampal neurogenesis be a future drug target for treating temporal lobe epilepsy?
The dentate gyrus, a region of the hippocampal formation, displays the highest level of plasticity in the brain and exhibits neurogenesis all through life. Dentate neurogenesis, believed to be essential for learning and memory function, responds to physiological stimuli as well as pathological situations. The role of dentate neurogenesis in the pathophysiology of temporal lobe epilepsy (TLE) has received increased attention lately because of its disparate response in the early and chronic stages of the disease. Acute seizures or status epilepticus immensely enhance dentate neurogenesis and lead to an aberrant migration of newly born neurons into the dentate hilus and the formation of epileptogenic circuitry in the injured hippocampus. Conversely, spontaneous recurrent seizures that arise during chronic TLE are associated with dramatically reduced dentate neurogenesis. In this review, we discuss the potential significance of enhanced but abnormal neurogenesis taking place shortly after brain injury or the status epilepticus towards the development of chronic epilepsy, and prospective implications of dramatically waned dentate neurogenesis occurring during chronic epilepsy for learning and memory function and depression in TLE. Furthermore, we confer whether hippocampal neurogenesis is a possible drug target for preventing TLE after brain injury or the status epilepticus, and for easing learning and memory impairments during chronic epileptic conditions. Additionally, we discuss some possible drugs and approaches that need to be evaluated in future in animal models of TLE to further understand the role of neurogenesis in the pathogenesis of TLE and whether modulation of neurogenesis is useful for treating TLE.
Department of Surgery (Neurosurgery) Duke University Medical Center, Durham, NC 27710, USA.
Ramkumar
R
Kuruba
Ashok K
AK
Shetty
D000818:Animals; D002908:Chronic Disease; D018891:Dentate Gyrus / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology; D006801:Humans; D012640:Seizures / Q000473:pathology