Activity-dependent NFATc3 nuclear accumulation in pericytes from cortical parenchymal microvessels.
The calcium-dependent transcription factor NFATc3, which is a member of the nuclear factor of activated T cells (NFAT) family of transcription factors, is critical for embryonic vascular development and differentiation. Despite its potential importance, nothing is known about NFATc3 regulation in the brain microcirculation. In the present study, we sought to investigate the role that glutamate, possibly through astrocytic communication, plays in the control of NFATc3 regulation in pericytes from parenchymal microvessels. Coronal cortical slices from neonatal rats were subjected to electrical field stimulation or were treated with the metabotropic glutamate receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD). NFATc3, glial fibrillary acidic protein (an astrocyte-specific marker), and platelet-derived growth factor-beta-receptor (a pericyte-specific marker) were detected by immunofluorescence. Electrical field stimulation induced NFATc3 nuclear accumulation in pericytes. This response was dependent on neuronal activity and group I metabotropic glutamate receptor (mGluR) activation. In addition, t-ACPD significantly increased NFATc3 nuclear accumulation in both astrocytes and pericytes. NFATc3 nuclear accumulation in pericytes was prevented when astrocytic function was abolished with the gliotoxin L-alpha-aminoadipate or by the inhibition of calcineurin, cyclooxygenase, and nitric oxide synthase. This is the first study to report NFATc3 expression in pericytes from parenchymal microvessels and in astrocytes from native tissue. Our results suggest a model by which glutamate, via mGluR activation, may regulate gene transcription in pluripotent vascular pericytes.
Filosa
Jessica A
JA
Department of Psychiatry, University of Cincinnati, Cincinnati, OH 45237, USA. jessica.filosa@uc.edu
Nelson
Mark T
MT
Gonzalez Bosc
Laura V
LV
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply; D004558:Electric Stimulation; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D020286:Pericytes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists; D015398:Signal Transduction / Q000502:physiology
D050778:NFATC Transcription Factors; D018094:Receptors, Metabotropic Glutamate; C445503:transcription factor NF-AT c3; D018698:Glutamic Acid