Abstract
Acute seizure (AS) activity in old age has an increased predisposition for evolving into temporal lobe epilepsy (TLE). Furthermore, spontaneous seizures and cognitive dysfunction after AS activity are often intense in the aged population than in young adults. This could be due to an increased vulnerability of inhibitory interneurons in the aged hippocampus to AS activity. We investigated this issue by comparing the survival of hippocampal GABA-ergic interneurons that contain the neuropeptide Y (NPY) or the calcium binding protein parvalbumin (PV) between young adult (5-months old) and aged (22-months old) F344 rats at 12 days after three-hours of AS activity. Graded intraperitoneal injections of the kainic acid (KA) induced AS activity and a diazepam injection at 3 hours after the onset terminated AS-activity. Measurement of interneuron numbers in different hippocampal subfields revealed that NPY+ interneurons were relatively resistant to AS activity in the aged hippocampus in comparison to the young adult hippocampus. Whereas, PV+ interneurons were highly susceptible to AS activity in both age groups. However, as aging alone substantially depleted these populations, the aged hippocampus after three-hours of AS activity exhibited 48% reductions in NPY+ interneurons and 70% reductions in PV+ interneurons, in comparison to the young hippocampus after similar AS activity. Thus, AS activity-induced TLE in old age is associated with far fewer hippocampal NPY+ and PV+ interneuron numbers than AS-induced TLE in the young adult age. This discrepancy likely underlies the severe spontaneous seizures and cognitive dysfunction observed in the aged people after AS activity.
Highlights
Epilepsy, characterized by intermittent and unpredictable occurrence of seizures, affects over 50 million people worldwide [1] and over two million people in the United States [2]
The density of neuropeptide Y (NPY)+ interneurons in all subfields appeared greater in young rats (Fig. 1 [A2–A4] than in aged rats (Fig. 2 [A2–A4]), which is consistent with the previous reports [18,38]
To analyze the effects of age and Acute seizure (AS) activity, and the potential role of interaction between age and AS activity in the overall reduction of NPY+ interneurons, two-way ANOVA analysis was performed for NPY+ neuron numbers from all four groups
Summary
Epilepsy, characterized by intermittent and unpredictable occurrence of seizures, affects over 50 million people worldwide [1] and over two million people in the United States [2]. More than a third of epileptic patients are over 65 years of age, as old age is the most common time for presenting seizures [3,4,5]. This may be due to an increased excitability of principal hippocampal neurons seen with age [6211]. From this perspective, the survival and connectivity of inhibitory interneurons in the aged hippocampus have received notice. Maintenance of a critical number of GABA-synthesizing interneurons in different subfields of the hippocampus appears essential for stabilizing excitatory influences and synchronizing principal excitatory neuron populations in the hippocampus [12,15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
