• Open Access

Vulnerability of hippocampal GABA-ergic interneurons to kainate-induced excitotoxic injury during old age

Authors

  • Ashok K. Shetty,

    Corresponding author
    1. Medical Research and Surgery Services, Veterans Affairs Medical Center, Durham, NC, USA
    2. Department of Surgery (Division of Neurosurgery), Duke University Medical Center, Durham, NC, USA
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  • Bharathi Hattiangady,

    1. Medical Research and Surgery Services, Veterans Affairs Medical Center, Durham, NC, USA
    2. Department of Surgery (Division of Neurosurgery), Duke University Medical Center, Durham, NC, USA
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  • Muddanna S. Rao

    1. Medical Research and Surgery Services, Veterans Affairs Medical Center, Durham, NC, USA
    2. Department of Surgery (Division of Neurosurgery), Duke University Medical Center, Durham, NC, USA
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Correspondence to: Ashok K. SHETTY, Ph.D., Professor, Division of Neurosurgery, DUMC Box 3807, Duke University Medical Center, Durham, NC 27710, USA.
Tel.: 919-286-0411, ext. 7096
Fax: 919-286-4662
E-mail: ashok.shetty@duke.edu

Abstract

Hippocampal inhibitory interneurons expressing glutamate decarboxylase-67 (GAD-67) considerably decline in number during old age. Studies in young adult animals further suggest that hippocampal GAD-67+ interneuron population is highly vulnerable to excitotoxic injury. However, the relative susceptibility of residual GAD-67+ interneurons in the aged hippocampus to excitotoxic injury is unknown. To elucidate this, using both adult and aged F344 rats, we performed stereological counting of GAD-67+ interneurons in different layers of the dentate gyrus and CA1 & CA3 sub-fields, at 3 months post-excitotoxic hippocampal injury inflicted through an intracerebroventricular administration of kainic acid (KA). Substantial reductions of GAD-67+ interneurons were found in all hippocampal layers and sub-fields after KA-induced injury in adult animals. Contrastingly, there was no significant change in GAD-67+ interneuron population in any of the hippocampal layers and sub-fields following similar injury in aged animals. Furthermore, the stability of GAD-67+ interneurons in aged rats after KA was not attributable to milder injury, as the overall extent of KA-induced hippocampal principal neuron loss was comparable between adult and aged rats. Interestingly, because of the age-related disparity in vulnerability of interneurons to injury, the surviving GAD-67+ interneuron population in the injured aged hippocampus remained comparable to that observed in the injured adult hippocampus despite enduring significant reductions in interneuron number with aging. Thus, unlike in the adult hippocampus, an excitotoxic injury to the aged hippocampus does not result in significantly decreased numbers of GAD-67+ interneurons. Persistence of GAD-67+ interneuron population in the injured aged hippocampus likely reflects an age-related change in the response of GAD-67+ interneurons to excitotoxic hippocampal injury. These results have implications towards understanding mechanisms underlying the evolution of initial precipitating injury into temporal lobe epilepsy in the elderly population.

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