Diminished gastric prokinetic response to ghrelin in a rat model of spinal cord injury

Besecker, Emily Swartz; White, Amanda R; Holmes, Gregory M.

doi:10.1111/nmo.13258

Cited by 8 publications

(5 citation statements)

References 58 publications

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“…These data suggest that T3-SCI provokes unparalleled structural and functional changes with variable duration. Our accumulating evidence suggests that SCI provokes impairments in the vagal afferent signaling necessary for proper GI reflexes (Besecker et al, 2018;Holmes, 2012;Tong et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…The apparent reduction of GI chemosensory signaling to medullary neural circuits (Besecker et al, 2018;Tong et al, 2011) raises the question of pathophysiological remodeling of vagal afferent fibers following SCI. Using molecular techniques and in vivo electrophysiological recordings of the vagal afferent fibers innervating the stomach, we tested the hypothesis that acute and chronic high-thoracic (spinal level T3) SCI attenuate gastric mechanosensitivity.…”

Section: Introductionmentioning

confidence: 99%

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Gastric vagal afferent neuropathy following experimental spinal cord injury

Besecker

Blanke

Deiter

et al. 2020

Experimental Neurology

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Dramatic impairment of gastrointestinal (GI) function accompanies high-thoracic spinal cord injury (T3-SCI). The vagus nerve contains mechano-and chemosensory fibers as well as the motor fibers necessary for the central nervous system (CNS) control of GI reflexes. Cell bodies for the vagal afferent fibers are located within the nodose ganglion (NG) and the majority of vagal afferent axons are unmyelinated C fibers that are sensitive to capsaicin through activation of transient receptor potential vanilloid-1 (TRPV1) channels. Vagal afferent fibers also express receptors for GI hormones, including cholecystokinin (CCK). Previously, T3-SCI provokes a transient GI inflammatory response as well as a reduction of both gastric emptying and centrallymediated vagal responses to GI peptides, including CCK. TRPV1 channels and CCK-A receptors (CCKar) expressed in vagal afferents are upregulated in models of visceral inflammation. The present study investigated whether T3-SCI attenuates peripheral vagal afferent sensitivity through plasticity of TRPV1 and CCK receptors.Vagal afferent response to graded mechanical stimulation of the stomach was significantly attenuated by T3-SCI at 3-day and 3-week recovery. Immunocytochemical labeling for CCKar and TRPV1 demonstrated expression on dissociated gastric-projecting NG neurons. Quantitative assessment of mRNA expression by qRT-PCR revealed significant elevation of CCKar and TRPV1 in the whole NG following T3-SCI in 3-day recovery, but levels returned to normal after 3-weeks. Three days after injury, systemic administration of CCK-8s showed a significantly diminished gastric vagal afferent response in T3-SCI rats compared to control rats while systemic capsaicin infusion revealed a significant elevation of vagal response in T3-SCI vs control rats.These findings demonstrate that T3-SCI provokes peripheral remodeling and prolonged alterations in the response of vagal afferent fibers to the physiological signals associated with digestion.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gastric vagal afferent neuropathy following experimental spinal cord injury

Besecker

Blanke

Deiter

et al. 2020

Experimental Neurology

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“…Importantly, GHSR signaling does not specifically recruit any of the referred signaling proteins and, consequently, the referred functional studies may involve indirect actions of ghrelin on the DMNV. Electrophysiological recordings in rat brain slices indicated that ghrelin increases the frequency but does not affect the amplitude of spontaneous glutamatergic currents of DMNV neurons, an indication that such effect is mainly indirect ( Besecker et al, 2018 , Swartz et al, 2014 ). GHSR mRNA is present in the Amb of rats and mice, as revealed by ISH ( Bron et al, 2013 , Scott et al, 2012 , Zigman et al, 2006 ), and fluorescent cells were observed in the Amb of the GHSR-eGFP mice ( Mani et al, 2014 ).…”

Section: Evidences Unmasking Direct Targets Of Ghrelin At the Vagus N...mentioning

confidence: 96%

The controversial role of the vagus nerve in mediating ghrelin's actions: gut feelings and beyond

Perelló

Cornejo

Francesco

et al. 2022

IBRO Neuroscience Reports

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“…Neuroendocrine activity is regulated by neural and humoral factors, including autonomic nerve activity (Besecker et al, 2018 ; Breit et al, 2018 ; Bonaz, 2022 ). For example, both intrapancreatic ganglia and extrapancreatic nerves have an important influence on pancreatic endocrine function (Li et al, 2019 ).…”

Section: Neural Regulation Of Neuroendocrine Activitymentioning

confidence: 99%