Chronic exposure to the chemokine CCL3 enhances neuronal network activity in rat hippocampal cultures.
We examined the effect of chronic CCL3 treatment on the properties of cultured rat hippocampal neurons to gain an understanding of the neuronal effects of CCL3 during neuroinflammatory disorders. Western blot assays showed that chronic exposure to CCL3 altered the level of specific neuronal and glial proteins and that CCL3 had no effect on neuronal survival. CCL3 treatment also altered intracellular Ca(2+) dynamics and increased Ca(2+) levels in hippocampal neurons, measured by fura-2 imaging techniques. Additionally, chronic CCL3 increased NMDA-evoked Ca(2+) signals in the hippocampal neurons and increased NMDA receptor levels. These CCL3-induced neuroadaptive changes could play an important role in the CNS dysfunction associated with CNS disorders with a neuroinflammatory component.
Kuijpers
M
M
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA.
van Gassen
K L I
KL
de Graan
P N E
PN
Gruol
D
D
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D054405:Chemokine CCL3 / Q000494:pharmacology*; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D009415:Nerve Net / Q000187:drug effects*; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009924:Organ Culture Techniques; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D055366:Synaptic Potentials / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D054405:Chemokine CCL3; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D011810:Quinoxalines; D017470:Receptors, Glutamate; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; D015763:2-Amino-5-phosphonovalerate; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D010751:Phosphopyruvate Hydratase; D002118:Calcium