Vulnerability of the Dentate Gyrus to Aging and Intracerebroventricular Administration of Kainic Acid

Abstract

The hippocampal formation is highly vulnerable to the aging process, demonstrating functional alterations in circuitry with aging. Aging may also change the sensitivity of the hippocampal formation to excitotoxic lesions. In this study, using young adult, middle aged, and aged Fischer 344 rats, we evaluated morphometric changes in the dentate gyrus as a function of age and also in response to an administration of an excitotoxin (kainic acid) into the right lateral ventricle. The dentate gyrus was measured for changes in the area of dentate hilus and the dentate granule cell layer, alterations in the width of the dentate granule cell layer, and degree of dentate hilar cell loss. With aging, the hilar area increased in size while the area and width of the dentate granule cell layer remained constant. However, the most striking change with aging was a significant reduction in the number of dentate hilar neurons. Intracerebroventricular kainic acid produced consistent lesions in the entire ipsilateral CA3 region, and the size of CA3 lesion was identical in all three ages of animals. Following the lesion, areas of both the dentate hilus and the granule cell layer were significantly decreased in only young adult and middle aged animals whereas the width of the dentate granule cell layer was significantly increased only in the middle aged group. In contrast, dentate hilar neurons were significantly reduced in all ages of animals with the maximum reductions in neuron number observed in the aged group. Thus, aging in the dentate gyrus is characterized by a significantly decreased number of dentate hilar neurons and also a significantly increased susceptibility of dentate hilar neurons to excitotoxic damage.