title: Neuroplasticity in the smooth muscle of the myenterically and extrinsically denervated rat jejunum.
abstract: The objective of this study was to examine the effects of two different denervation procedures on the distribution of nerve fibers and neurotransmitter levels in the rat jejunum. Extrinsic nerves were eliminated by crushing the mesenteric pedicle to a segment of jejunum. The myenteric plexus and extrinsic nerves were eliminated by serosal application of the cationic surfactant benzyldimethyltetradecylammonium chloride (BAC). The effects of these two denervation procedures were evaluated at 15 and 45 days. The level of norepinephrine in whole segments of jejunum was initially reduced by more than 76% after both denervation procedures, but by 45 days the level of norepinephrine was the same as in control tissue. Tyrosine hydroxylase (noradrenergic nerve marker) immunostaining was absent at 15 days, but returned by 45 days. However, the pattern of noradrenergic innervating axons was altered in the segment deprived of myenteric neurons. Immunohistochemical studies showed protein gene product 9.5 (PGP 9.5)-immunoreactive fibers in whole-mount preparations of the circular smooth muscle in the absence of the myenteric plexus and extrinsic nerves. At 45 days, the number of nerve fibers in the circular smooth muscle increased. Vasoactive intestinal polypeptide (VIP)-immunoreactive fibers, a subset of the PGP 9.5 nerve fibers, were present in the circular smooth muscle at both time points examined. Choline acetyltransferase (CAT) activity and VIP and leucine enkephalin levels were measured in separated smooth muscle and submucosa-mucosal layers of the denervated jejunum. VIP and leucine-enkephalin levels were no different from control in tissue that was extrinsically denervated alone. However, the levels of these peptides were elevated two-fold in the smooth muscle 15 and 45 days after myenteric and extrinsic denervation. In the submucosa-mucosa, VIP and leucine enkephalin levels also were elevated two-fold at 15 days, but comparable to control at 45 days. CAT activity was equal to control in the smooth muscle but elevated two-fold in the submucosa-mucosa at both times. These results provide evidence for innervation of the circular smooth muscle by the submucosal plexus. Moreover, these nerve fibers originating from the submucosal plexus proliferate in the absence of the myenteric plexus. Furthermore, the myenteric neurons appear to be essential for normal innervation of the smooth muscle by the sympathetic nerve fibers. It is speculated that the sprouting of the submucosal plexus induced by myenteric plexus ablation is mediated by increased production of trophic factors in the hyperplastic smooth muscle.
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison 53706.
authors.forename: M S
authors.initials: MS
authors.lastname: Luck
authors.forename: J L
authors.initials: JL
authors.lastname: Dahl
authors.forename: M G
authors.initials: MG
authors.lastname: Boyeson
authors.forename: P
authors.initials: P
authors.lastname: Bass
mesh_terms: D000818:Animals; D001548:Benzalkonium Compounds; D015415:Biomarkers; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004743:Enkephalin, Leucine / Q000032:analysis; D007583:Jejunum / Q000294:innervation*; D009130:Muscle, Smooth / Q000294:innervation*; D009197:Myenteric Plexus / Q000293:injuries / Q000502:physiology*; D009409:Nerve Crush; D009419:Nerve Tissue Proteins / Q000032:analysis; D009473:Neuronal Plasticity; D009638:Norepinephrine / Q000032:analysis; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013563:Sympathectomy, Chemical; D013869:Thiolester Hydrolases / Q000032:analysis; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D043222:Ubiquitin Thiolesterase; D014660:Vasoactive Intestinal Peptide / Q000032:analysis
chemical_list: D001548:Benzalkonium Compounds; D015415:Biomarkers; D009419:Nerve Tissue Proteins; C005883:zephiramine; D014660:Vasoactive Intestinal Peptide; D004743:Enkephalin, Leucine; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D009638:Norepinephrine