Persistent hippocampal neurogenesis and epilepsy

Abstract

The dogma of no neuronal production, or neurogenesis, in the adult mammalian brain slowly has been laid to rest over the past five decades. Resounding experimental evidence indicates that neural stem cells and neurogenesis persist in at least two regions of the adult mammalian brain, the hippocampal dentate gryus and striatal subventricular zone of the lateral ventricles (Ming & Song, 2005). In the adult mammalian dentate gyrus, neural stem cells in a proliferative zone under the granule cell layer give rise to dentate granule cells (DGCs) throughout life. Although important questions about the biological function of adult neurogenesis remain unanswered, a growing body of data suggests that adult neurogenesis adds an additional layer of plasticity into the hippocampal circuitry (Bruel-Jungerman et al., 2007). This plasticity likely plays a role in specific forms of hippocampus-dependent learning and memory. The recognition of persistent neurogenesis in the adult mammalian brain has led to studies of how injury influences neurogenesis. Interestingly, nearly all types of brain insults appear to stimulate neurogenesis in the adult neurogenic zones (Parent, 2003). These findings have led to two distinct areas of inquiry with respect to epileptogenic brain injuries. The more obvious question is the following: Are neural stem cells that persist in the adult capable of repairing the injured brain if stimulated appropriately? If so, do they accomplish this through compensatory effects on neural networks or by replacing lost cells? General interest and advances in neural stem cell biology have led to related investigations of whether transplanted neural progenitors may serve similar therapeutic functions. The other main question regarding postnatal or adult hippocampal neurogenesis and epilepsy involves the idea that abnormally occurring neurogenesis is critically involved in aberrant plasticity during epileptogenesis. Simply stated, if new neurons integrate abnormally into existing circuits after an epileptogenic insult, do they contribute to the development of epilepsy or associated morbidities such as memory dysfunction or depression? These ideas relate to both acute changes in neurogenesis after injury and chronic dysfunction of the neural stem cell niche or environment.