Viral-Induced Dysfunction of Sensory Neurons

Ziegler, Richard

Abstract

Normal behavior depends upon the proper functioning of the nervous system. Intact neural circuits possessing correct intracellular and intercellular neuronal communications are largely responsible for this functioning. Alteration or disruption of this communication can lead to mental disease. These alterations may be the result of genetic defects, trauma, toxic substances, or infectious agents which either destroy groups or populations of neurons or cause improper communication within or between neurons. Viruses are well known for their ability to infect neurons and kill them during the process of viral replication. Poliovirus infections are a classic example. This loss of neurons results in neural dysfunction with concomitant disease. The ability of viruses to cause neural dysfunction by altering neuronal function is not well documented. This proposal is designed to determine whether noncytolytic virus infections of neurons can cause neuronal dysfunction and thereby play a role in mental disease. Specifically, we are requesting funds for a pilot study to determine if representative neurotrophic viruses, 1) measles virus, 2) mumps virus, 3) a neurotrophic retrovirus can alter specific aspects of neuronal function, i.e. ligand and voltage-gated ionic channels and neuropeptide metabolism. The functional properties that will be examined include generation of action potentials, neurochemical receptor-mediated membrane excitation, neurochemical modulation of ionic channels and neuropeptide content and release. All of these parameters are important for normal functioning of the brain and therefore good mental health. These studies will be performed in vitro with rat or mouse sensory neurons as our """"""""model"""""""" neurons. The proposal is not designed to prove a specific noncytolytic virus is involved in a specific mental health problem but to demonstrate they have this potential. Future proposals may address this question.