Myenteric Neuroplasticity Due to Experimental Colitis

Project: Research project

Description

DESCRIPTION (provided by applicant): The motor disturbances that are present
during inflammation of the bowel reflect a significant interaction between
inflammatory mediators and the enteric nervous system. The neural mechanisms of
inflammation-induced dysmotility are currently unknown. Using a guinea pig
model of experimental colitis, the specific aims of this proposal are to test
two hypotheses. The first hypothesis is that inflammation causes an increased
excitability in intrinsic primary afferent neurons, which leads to an imbalance
in the peristaltic reflex circuit. This hypothesis will be explored by
addressing two questions: 1) Do the electrical or synaptic properties of
functionally identified myenteric neurons change during experimental colitis?
2) Is the neurogenic propulsive motor activity of the intact guinea pig colon
altered during inflammation? The second hypothesis is that changes in the
peristaltic reflex circuit, induced by inflammation, persist following
histopathological recovery. To test this hypothesis two question will be
addressed: 1) Do changes in the electrical or synaptic properties functionally
identified myenteric neurons persist or arise following histological recovery
from inflammation: 2) Do changes to the neurogenic propulsive motor activity of
the intact colon persist or arise following recovery from inflammation? In
conducting these studies, we will implement integrated combinations of
techniques, including intracellular recording and labeling of neurons,
retrograde axonal tracing, immunohistochemistry, and motility assays. These
results will advance our understanding of the mechanisms of neuro-immune
integration and motility disturbances associated with inflammatory bowel
disease and functional bowel disorders.
StatusActive
Effective start/end date9/1/01 → …

Funding

  • National Institutes of Health: $40,196.00
  • National Institutes of Health: $46,192.00

Fingerprint

Neuronal Plasticity
Colitis
Inflammation
Neurons
Reflex
Motor Activity
Guinea
Enteric Nervous System
Afferent Neurons
Guinea Pigs
Colon
Immunohistochemistry

ASJC

  • Medicine(all)