Aging of the gut's nervous system: Onsets and rates of loss of both vagal endings and myenteric neurons differ between organs in the Fischer 344 rat

Robert Jay Phillips, Purdue University

Abstract

To explore the effects of aging on the vagal innervation of the GI tract, male Fischer 344 rats at 3 and 24 months of age were injected in the left nodose ganglion with 3 μl of either 4% wheat germ agglutinin-horseradish peroxidase (to label sensory endings) or 1% cholera toxin subunit B-horseradish peroxidase (to label motor endings). The ventral side of the stomach and duodenum were prepared as wholemounts and processed with tetramethyl benzidine. In addition, to study age-related changes in the myenteric plexus, the stomach, small intestine, and large intestine from 3-, 12-, 21-, 24- and 27-month-old rats were prepared as wholemounts and processed with Cuprolinic Blue (to stain the neurons). Vagal sensory endings, motor terminal profiles, and myenteric neurons were counted and mapped with a sampling grid. The densities of the vagal and myenteric innervation of the stomach were stable between the ages of 3 and 24 months, however, a decrease in the number of myenteric neurons was noted at 27 months. In the small and large intestine, myenteric cell loss occurred at 12 months of age, progressed with age, and appeared to be governed by several general principles: (a) the rate of cell loss was organ-specific, with an oral-to-anal gradient in severity, (b) the rate of cell loss differed between regions within an organ, and (c) for given regions, cell losses progressed linearly with increasing age. These and additional findings suggest that a positive relationship may exist between the density of extrinsic innervation and myenteric neuron survival, however, whether this results from the extrinsic innervation protecting, and/or other factor(s) rescuing, myenteric neurons from attrition remains to be determined.

Degree

Ph.D.

Advisors

Powley, Purdue University.

Subject Area

Neurology|Psychobiology

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