The microenvironment in chronic pancreatitis and pancreatic cancer induces neuronal plasticity

Abstract

Intrapancreatic microenvironment in CP and PCa induces neuroplastic alterations under in-vitro conditions, leading to increased neural density and hypertrophy. Thus, due to its neurotrophic attributes, the intrapancreatic microenviroment in CP and PCa seems to be a key player in the generation of pancreatic neuropathy and neuroplasticity.

Hyperglycemic tumor microenvironment induces perineural invasion in pancreatic cancer

“…14 The intrapancreatic microenvironment in patients with chronic pancreatitis and PanCa induces neurite outgrowth, complex branching patterns, perikaryonal hypertrophy, and increased glial density of DRGs in vitro, which play a key role in the generation of pancreatic neuropathy and neuroplasticity. 28 The present study described an interesting phenomenon in which regeneration of neurites is increased and the SCs migration outline is shrunk to a similar degree in newly formed hyperglycemic tumor microenvironments. The increased neurite regeneration is extended directly toward and interacts with PanCa cancer, which is also extended toward DRGs.…”

Simulating Pancreatic Neuroplasticity: <em>In Vitro</em> Dual-neuron Plasticity Assay

“…Depending on the concentration to be used in the assay, the final concentration of the extract or supernatant in the neuronal medium should be 100 µg/ml 5,8 .…”

“…Such indicators can easily be derived from adequate in vitro models in which isolated cell subtypes from the complex microenvironment of an in vivo system can be selectively cocultured in a heterotypic manner [4][5][6][7] . The modulation of molecular targets in such a heterotypic culture setting is on average technically less cumbersome, faster, and can therefore aid in the prefiltering of worthwhile targets for verification in in vivo studies.…”

“…Here, neurons derived from newborn rat dorsal root ganglia (DRG) or myenteric plexus (MP) were exposed to tissue extracts from surgically resected PCa or CP tissues specimens and compared to those cultured in normal human pancreas (NP) tissue extracts 5 . Instead of tissue extracts, one can also use cell line supernatants to study the impact of selected cell types on neuroplasticity.…”

Pathogenesis and Treatment of Pain in Chronic Pancreatitis

“…However, the study of these morphological alterations in a functional manner is limited by the still ongoing lack of animal models that exhibit similar neuroplastic-neuropathic alterations. Nonetheless, in recent in vitro models, stimulation of dorsal root ganglia neurons with pancreatic tissue extracts of resected CP patients could mimic the increased neural density and hypertrophy or neurons (14). In the same setting, the blockade of the neurotrophic factor neurturin, similar to the blockade of NGF or TGF-beta-1, could suppress the neurotrophic potential of CP extracts (17).…”