Impaired activation of celiac ganglion neurons in vivo after damage to their sympathetic nerve terminals

Abstract

Because damage to sympathetic nerve terminals occurs in a variety of diseases, we tested the hypothesis that nerve terminal damage per se is sufficient to impair ganglionic neurotransmission in vivo. First, we measured the effect of nerve terminal damage produced by the sympathetic nerve terminal toxin 6-hydroxydopamine (6-OHDA) on ganglionic levels of several neurotrophins thought to promote neurotransmission. 6-OHDA-induced nerve terminal damage did not decrease the expression of neurotrophin-4 or brain-derived neurotrophic factor mRNA in the celiac ganglia but did decrease the ganglionic content of both nerve growth factor protein (nadir = -63%) and the mRNA of the alpha-3 subunit of the nicotinic cholinergic receptor (nadir = -49%), a subunit required for neurotransmission. Next, we tested whether this degree of receptor deficiency was sufficient to impair activation of celiac ganglia neurons. Impaired fos mRNA responses to nicotine administration in the celiac ganglia of 6-OHDA-pretreated rats correlated temporally with suppressed expression of functional nicotinic receptors. We verified by Fos protein immunohistochemistry that this ganglionic impairment was specific to principal ganglionic neurons. Last, we tested whether centrally initiated ganglionic neurotransmission is also impaired following nerve terminal damage. The principal neurons in rat celiac ganglia were reflexively activated by 2-deoxy-glucose-induced glucopenia, and the Fos response in the celiac ganglia was markedly inhibited by pretreatment with 6-OHDA. We conclude that sympathetic nerve terminal damage per se is sufficient to impair ganglionic neurotransmission in vivo and that decreased nicotinic receptor production is a likely mediator. Keywords 6-hydroxydopamine; neurotransmission; nerve growth factor; nicotinic acetylcholine receptor; fos mRNA; Fos protein Studies of the effects of damage to sympathetic nerve fibers on their cell bodies have traditionally relied on the extreme experimental maneuver of complete axotomy. Such studies have proven valuable both for demonstrating the proof of principle that axonal damage can produce cell body dysfunction and for exploring the mechanisms involved. It is possible to extrapolate from these earlier studies that a less severe neural insult, such as damage restricted to nerve terminals, would also impair ganglionic function, but this hypothesis has not been directly tested. Furthermore, cell body dysfunction induced by axotomy has no influence on neurotransmitter release from nerve terminals because by definition axotomy severs all connection between the cell body and its terminals. In contrast, impaired cell body function following incomplete nerve terminal damage can have functional consequences by impairing neurotransmitter release from spared terminals. Thus, we thought it important to determine the

Neuronal degeneration in autonomic nervous system of Dystonia musculorum mice

“…This investigation also demonstrated the sympathetic denervation of sweat glands in footpads and parasympathetic denervation of irises in eyes of dt/dt mutants. The terminal endings of the sympathetic nerve commonly degenerate more quickly than the proximal portions of the degenerating sympathetic ganglia neurons [ 29 ]. Skin denervation studies have established an early sign of neuropathy before ganglionopathy is detected [ 30 ].…”

Short-term diabetic hyperglycemia suppresses celiac ganglia neurotransmission, thereby impairing sympathetically mediated glucagon responses

“…The extraction, reverse transcription, and RT-PCR analysis of ganglia were performed as we have previously described in detail (32). The extraction, reverse transcription, and RT-PCR analysis of ganglia were performed as we have previously described in detail (32).…”

Nicotinic Acetylcholine Receptor Involvement in Inflammatory Bowel Disease and Interactions with Gut Microbiota

“…Small and large intestines [26,27,43,45,46] Celiac ganglia c α3, α7 α3 * ,f , α7 f Distal esophagus, stomach, proximal duodenum, liver, biliary system, spleen, adrenal glands [47,48] Superior mesenteric ganglia c α7 α7 f Duodenum, jejunum, ileum, cecum, appendix, ascending colon, proximal transverse colon [47] Inferior mesenteric ganglia c,d α3, α5, β4 α3β4 * Distal transverse, descending, and sigmoid, colon, rectum, upper anal canal [49] Inferior hypogastric plexus c,d α3, β4, α7 unknown Urogential organs, pelvic viscera [50,51] Myenteric plexus c,d,e α3, α5, α7, β2, β4 α3β2 *, α3β4 *, α7…”