The goal of the proposed research is to determine if cellular or chemical factors encountered during maturation affect the expression of neurochemical membrane receptors on astroglia. There is overwhelming evidence which demonstrates that astroglia isolated from immature brain and grown in culture exhibit a variety of receptor systems which respond to neurochemical messages. Recent studies reported from this laboratory suggest that there are at least two pharmacologically-distinct populations of astroglia which can be distinguished on the basis of their expresion of beta-adrenergic receptors. These results were obtained using a novel technique which enables us to examine receptors via receptor autoradiography on immunocytochemically-identified cells. Our system includes a microcomputer-based video image digitizer which enables us to quantify autoradiographic data. Using this approach, it will be possible to examine a number of important questions concerning the pharmacological properties of astrocytes which had not previously been approachable. The following three general questions will be addressed in this proposal. First, do astroglia continue to express membrane receptors following maturation in vitro or in vivo? Second, do immature astroglia or mature astrocytes vary in their expression of membrane receptors as a function of the brain region from which they are prepared? Third, do specific populations of neurons, identified immunocytochemically, affect the expression of astroglial membrane receptors? An examination of these questions should provide valuable information concerning the manner through which neurons and astrocytes communicate during normal and abnormal brain function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020212-03
Application #
3400456
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1983-12-01
Project End
1987-03-31
Budget Start
1985-12-01
Budget End
1987-03-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Khakh, Baljit S; McCarthy, Ken D (2015) Astrocyte calcium signaling: from observations to functions and the challenges therein. Cold Spring Harb Perspect Biol 7:a020404
Song, Yurong; Zhang, Qian; Kutlu, Burak et al. (2013) Evolutionary etiology of high-grade astrocytomas. Proc Natl Acad Sci U S A 110:17933-8
Agulhon, Cendra; Boyt, Kristen M; Xie, Alison Xiaoqiao et al. (2013) Modulation of the autonomic nervous system and behaviour by acute glial cell Gq protein-coupled receptor activation in vivo. J Physiol 591:5599-609
Agulhon, Cendra; Fiacco, Todd A; McCarthy, Ken D (2010) Hippocampal short- and long-term plasticity are not modulated by astrocyte Ca2+ signaling. Science 327:1250-4
Petravicz, Jeremy; Fiacco, Todd A; McCarthy, Ken D (2008) Loss of IP3 receptor-dependent Ca2+ increases in hippocampal astrocytes does not affect baseline CA1 pyramidal neuron synaptic activity. J Neurosci 28:4967-73
Agulhon, Cendra; Petravicz, Jeremy; McMullen, Allison B et al. (2008) What is the role of astrocyte calcium in neurophysiology? Neuron 59:932-46
Casper, Kristen B; McCarthy, Ken D (2006) GFAP-positive progenitor cells produce neurons and oligodendrocytes throughout the CNS. Mol Cell Neurosci 31:676-84
Howe, D G; McCarthy, K D (2000) Retroviral inhibition of cAMP-dependent protein kinase inhibits myelination but not Schwann cell mitosis stimulated by interaction with neurons. J Neurosci 20:3513-21
Shao, Y; McCarthy, K D (1997) Responses of Bergmann glia and granule neurons in situ to N-methyl-D-aspartate, norepinephrine, and high potassium. J Neurochem 68:2405-11
Porter, J T; McCarthy, K D (1996) Hippocampal astrocytes in situ respond to glutamate released from synaptic terminals. J Neurosci 16:5073-81

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