Implications of decreased hippocampal neurogenesis in chronic temporal lobe epilepsy.
Temporal lobe epilepsy (TLE), characterized by spontaneous recurrent motor seizures (SRMS), learning and memory impairments, and depression, is associated with neurodegeneration, abnormal reorganization of the circuitry, and loss of functional inhibition in the hippocampal and extrahippocampal regions. Over the last decade, abnormal neurogenesis in the dentate gyrus (DG) has emerged as another hallmark of TLE. Increased DG neurogenesis and recruitment of newly born neurons into the epileptogenic hippocampal circuitry is a characteristic phenomenon occurring during the early phase after the initial precipitating injury such as status epilepticus. However, the chronic phase of the disease displays substantially declined DG neurogenesis, which is associated with SRMS, learning and memory impairments, and depression. This review focuses on DG neurogenesis in the chronic phase of TLE and first confers the extent and mechanisms of declined DG neurogenesis in chronic TLE. The available data on production, survival and neuronal fate choice decision of newly born cells, stability of hippocampal stem cell numbers, and changes in the hippocampal microenvironment in chronic TLE are considered. The next section discusses the possible contribution of declined DG neurogenesis to the pathophysiology of chronic TLE, which includes its potential effects on spontaneous recurrent seizures, cognitive dysfunction, and depression. The subsequent section considers strategies that may be useful for augmenting DG neurogenesis in chronic TLE, which encompass stem cell grafting, administration of distinct neurotrophic factors, physical exercise, exposure to enriched environment, and antidepressant therapy. The final section suggests possible ramifications of increasing the DG neurogenesis in chronic epilepsy.
Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Bharathi
B
Hattiangady
Ashok K
AK
Shetty
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002908:Chronic Disease; D004833:Epilepsy, Temporal Lobe / Q000473:pathology*; D006624:Hippocampus / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000473:pathology / Q000502:physiology