Age-related neuronal loss in the submucosal plexus of the colon of Fischer 344 rats

The submucosal plexus (SMP) of the large intestine plays important roles in secretion and motility, functions that are compromised in the aged. To determine the effects of aging on intrinsic SMP neurons and their extrinsic inputs, whole mounts from the colon of ad libitum fed virgin male Fischer 344 rats ranging in age from 6 to 27 months were processed to visualize neurons and nerve fibers immunoreactive for either tyrosine hydroxylase (TH-IR) or calcitonin gene-related peptide (CGRP-IR). Significant age-related loss of SMP neurons occurred as early as 12 months of age and progressed in a roughly linear manner with age, dropping, for example, by 38% in the distal colon. In aging rats, the colonic SMP routinely contained markedly swollen TH-IR axons and terminals and exhibited a reduction of ganglionic neuropil, whereas CGRP-IR fibers evidenced only modest axonopathies. These findings point to selective deterioration of the SMP and its extrinsic inputs as one possible mechanism for the age-related decline in large intestinal function evidenced in the elderly.