Pyramidal cells and cytochrome P450 epoxygenase products in the neurovascular coupling response to basal forebrain cholinergic input
| Autor: | Xin-Kang Tong, Edith Hamel, Claire H. Sandoe, Clotilde Lecrux, Ara Kocharyan |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Fluoroacetates Stimulation AMPA receptor Biology Pharmacology Nitric Oxide Receptors N-Methyl-D-Aspartate gamma-Aminobutyric acid Rats Sprague-Dawley 8 11 14-Eicosatrienoic Acid medicine Animals Citrates Evoked Potentials gamma-Aminobutyric Acid Basal forebrain Pyramidal Cells Glutamate receptor Amides Acetylcholine Rats Neurology nervous system Gene Expression Regulation Cyclooxygenase 2 Astrocytes Cerebrovascular Circulation Cholinergic NMDA receptor Original Article Neurology (clinical) Cardiology and Cardiovascular Medicine Neuroscience Proto-Oncogene Proteins c-fos Blood Flow Velocity medicine.drug |
| Zdroj: | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 32(5) |
| ISSN: | 1559-7016 |
| Popis: | Activation of the basal forebrain (BF), the primary source of acetylcholine (ACh) in the cortex, broadly increases cortical cerebral blood flow (CBF), a response downstream to ACh release. Although endothelial nitric oxide and cholinoceptive GABA (γ-aminobutyric acid) interneurons have been implicated, little is known about the role of pyramidal cells in this response and their possible interaction with astrocytes. Using c-Fos immunohistochemistry as a marker of neuronal activation and laser-Doppler flowmetry, we measured changes in CBF evoked by BF stimulation following pharmacological blockade of c-Fos-identified excitatory pathways, astroglial metabolism, or vasoactive mediators. Pyramidal cells including those that express cyclooxygenase-2 (COX-2) displayed c-Fos upregulation. Glutamate acting via NMDA, AMPA, and mGlu receptors was involved in the evoked CBF response, NMDA receptors having the highest contribution (∼33%). In contrast, nonselective and selective COX-2 inhibition did not affect the evoked CBF response (+0.4% to 6.9%, ns). The metabolic gliotoxins fluorocitrate and fluoroacetate, the cytochrome P450 epoxygenase inhibitor MS-PPOH and the selective epoxyeicosatrienoic acids (EETs) antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) all blocked the evoked CBF response by ∼50%. Together, the data demonstrate that the hyperemic response to BF stimulation is largely mediated by glutamate released from activated pyramidal cells and by vasoactive EETs, likely originating from activated astrocytes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|