To gain insights into the cognitive and developmental problems observed in pediatric neuroAIDS, the investigators propose to examine the effects of several cytokines and chemokines that are reported to be expressed in the CNS of HIV-1 infected patients. The investigators propose to use the cerebellar Purkinje cell culture system from embryonic rodents to determine the effects of recombinant cytokines and chemokines administered in three different modes; acute, chronic, and withdrawal. The effects will be determined by analysis of morphology, immunocytochemistry, electrophysiological recordings of various membrane ion channels and neurotransmitter receptor properties, as well as calcium imaging. By determining cytokine/chemokine-modulated changes in these parameters in developing neuronal system, the investigators wish to provide new insights into the potential roles of such factors in the CNS dysfunction in pediatric neuroAIDS.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD038231-04
Application #
6526360
Study Section
Special Emphasis Panel (ZRG1-AARR-5 (01))
Program Officer
Oster-Granite, Mary Lou
Project Start
1999-09-01
Project End
2003-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
4
Fiscal Year
2002
Total Cost
$282,813
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Gruol, Donna L (2015) IL-6 regulation of synaptic function in the CNS. Neuropharmacology 96:42-54
Gruol, Donna L; Nelson, Thomas E (2005) Purkinje neuron physiology is altered by the inflammatory factor interleukin-6. Cerebellum 4:198-205
Nelson, Thomas E; Netzeband, Jeffrey G; Gruol, Donna L (2004) Chronic interleukin-6 exposure alters metabotropic glutamate receptor-activated calcium signalling in cerebellar Purkinje neurons. Eur J Neurosci 20:2387-400
Nelson, Thomas E; Ur, Christina L; Gruol, Donna L (2002) Chronic interleukin-6 exposure alters electrophysiological properties and calcium signaling in developing cerebellar purkinje neurons in culture. J Neurophysiol 88:475-86
O'Barr, S A; Caguioa, J; Gruol, D et al. (2001) Neuronal expression of a functional receptor for the C5a complement activation fragment. J Immunol 166:4154-62