Recipient Organization
UNIVERSITY OF MISSOURI
(N/A)
COLUMBIA,MO 65211
Performing Department
V Biomedical Sciences
Non Technical Summary
People who are on bedrest for long periods of time, and astronauts returning from space undergo cardiovascular deconditioning. One of the problems associated with deconditioning is that people are less able to maintain their blood pressure on standing, and have a tendency to faint. The reasons for this are not clear. A strong possibility is that the reflexes that normally keep blood pressure are impaired. We have identified potential changes in brain regions involved in cardiovascular regulation in an animal model of cardiovascular deconditioning. This project will evaluate potential changes in neurons in the paraventricular nucleus (PVN), which is critical in controlling blood volume and blood pressure. We hypothesized that these neurons are more responsive to inhibition and less responsive to excitation. We will identify specifically PVN neurons involved in cardiovascular regulation using anatomical tract tracing techniques. We can then dissociate these neurons and
evaluate their intrinsic properties.
Animal Health Component
30%
Research Effort Categories
Basic
70%
Applied
30%
Developmental
(N/A)
Goals / Objectives
The overall objective of this proposal is to understand impairments in CNS regulatory mechanisms that contribute to the negative cardiovascular consequences of cardiovascular deconditioning. Specifically, we will examine individual PVN neurons involved in control of the sympathetic nervous system and how they are altered in hindlimb unloaded rats. We will test the hypothesis that cardiovascular deconditioning results in altered properties of PVN neurons involved in autonomic regulation so they are more responsive to inhibitory stimuli and less responsive to excitatory stimuli.
Project Methods
This project will focus on the intrinsic properties of neurons in the PVN that project to the region of the spinal cord that contains sympathetic preganglionic neurons. We will identify these neurons by injecting a fluorescent retrograde tracer, Fluorogold, into the spinal cord and allowing time for the tracer to be retrogradely transported to the PVN. Thus, any neurons that fluoresce can be assumed to project to the spinal cord. We will dissociate neurons from the PVN of control and HU rats. The neurons will then be visualized under a microscope, and spinally projecting neurons identified by their fluorescence. Identified neurons will be patch clamped to evaluate intrinsic properties of the neurons, including basic membrane and firing properties. We also will examine responses to excitatory and inhibitory agonists, as well as expression of the enzyme neuronal nitric oxide synthase (nNOS). These experiments will provide information regarding specific changes in PVN
neurons involved in control of sympathetic activity in response to cardiovascular deconditioning. These alterations likely have important implications for reflex control of the cardiovascular system and regulation of body fluid balance in deconditioned individuals.