University of Kentucky
Understanding Glutamate Neurotransmission Before, During, and After Status Epilepticus in Young and Aging Rats
Institution
University of Kentucky
Faculty Advisor/ Mentor
Michelle Stephens; Pete Huettl; Francois Pomerleau; Greg Gerhardt
Abstract
Temporal lobe epilepsy results from uncontrolled excitability of neurons, often in the hippocampus. The primary neurotransmitter affecting neuronal excitability in the adult hippocampus is glutamate, which is known to be altered during aging, manifesting as a loss of learning and memory capabilities. We believe that age-associated dysregulation of glutamate could also be a contributing factor to the increased onset and severity of seizure disorders in the elderly population. Our objective was to gain a better understanding of changes in glutamate regulation during aging, and how this may affect seizure severity in an animal model of human aging. We implanted novel microelectrode arrays into the hippocampus of young, late-middle aged and aged rats to measure real-time glutamate neurotransmission in awake rats. The aged hippocampus had significantly elevated basal glutamate compared to young rats (n = 30, p<0.05). Increased glutamate is known to be toxic to neurons. We also measured glutamate before, during, and after experimentally induced seizures. Based on our preliminary observations, the intensity of the seizure behavior correlates with age, showing that aged rats experience prolonged and more intense seizures. Additionally, during the seizures, we have repeatedly observed rapid and periodic glutamate oscillations indicating that glutamate is playing a critical role in seizure pathology. In the future, we will continue to examine the role of glutamate in a kindled model of epilepsy. This research will provide valuable insight into the potential role that glutamate plays in human epilepsy, especially in the elderly population, and may lead to the development of improved diagnostics and therapeutics.
Understanding Glutamate Neurotransmission Before, During, and After Status Epilepticus in Young and Aging Rats
Temporal lobe epilepsy results from uncontrolled excitability of neurons, often in the hippocampus. The primary neurotransmitter affecting neuronal excitability in the adult hippocampus is glutamate, which is known to be altered during aging, manifesting as a loss of learning and memory capabilities. We believe that age-associated dysregulation of glutamate could also be a contributing factor to the increased onset and severity of seizure disorders in the elderly population. Our objective was to gain a better understanding of changes in glutamate regulation during aging, and how this may affect seizure severity in an animal model of human aging. We implanted novel microelectrode arrays into the hippocampus of young, late-middle aged and aged rats to measure real-time glutamate neurotransmission in awake rats. The aged hippocampus had significantly elevated basal glutamate compared to young rats (n = 30, p<0.05). Increased glutamate is known to be toxic to neurons. We also measured glutamate before, during, and after experimentally induced seizures. Based on our preliminary observations, the intensity of the seizure behavior correlates with age, showing that aged rats experience prolonged and more intense seizures. Additionally, during the seizures, we have repeatedly observed rapid and periodic glutamate oscillations indicating that glutamate is playing a critical role in seizure pathology. In the future, we will continue to examine the role of glutamate in a kindled model of epilepsy. This research will provide valuable insight into the potential role that glutamate plays in human epilepsy, especially in the elderly population, and may lead to the development of improved diagnostics and therapeutics.