Systemic administration of kainic acid in adult rat stimulates expression of the chemokine receptor CCR5 in the forebrain.
As chemokines and their receptors are primarily expressed by glial cells in brain parenchyma, a model of glial cell proliferation may be useful to study the regulation of their expression in the brain. The well-established kainic acid seizure model was used in this study, focusing on the expression of the CCR5 chemokine receptor. Adult Sprague-Dawley rats were injected intraperitoneally with kainic acid (12 mg/kg), and in situ hybridization of CCR5 mRNA was performed at 12 h, 1, 3, or 7 days, posttreatment. Autoradiographic films and wet photographic emulsions demonstrated the very low expression of CCR5 mRNA in normal brain parenchyma, as well as in the microvasculature and ventricular/choroid plexus systems. After kainic acid treatment, brain CCR5 mRNA expression increased progressively from 12 h to 7 days, especially in the olfactory system, amygdaloid complex, thalamus, hippocampal formation, septum, and neocortex. This increase paralleled that of activated microglial cells as shown, using the microglial marker, OX-42. Moreover, CCR5 mRNA ISH combined with neuron-specific enolase immunocytochemistry showed that, in addition to its glial expression, CCR5 mRNA is expressed in neurons in the normal brain and, to a lesser extent, after kainate treatment due to neuronal losses. Finally, CCR5 protein is detected by immunocytochemistry in neurodegenerative areas in numerous glial cells, as well as in neurons, as clearly shown in the hippocampal formation. In summary, the chemokine receptor CCR5 is expressed by neuronal and non-neuronal cell types in the normal brain and is upregulated in both cell types after an insult.
Mennicken
Françoise
F
Department of Psychiatry, Douglas Hospital Research Centre, McGill University, LaSalle-Verdun, Québec, Canada.
Chabot
Jean-Guy
JG
Quirion
Rémi
R
D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018925:Chemokines / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019713:Receptors, CCR5 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D018925:Chemokines; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D009498:Neurotoxins; D012333:RNA, Messenger; D019713:Receptors, CCR5; D051926:Basigin; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid