Heart-Type Fatty Acid Binding Protein Regulates Dopamine D2Receptor Function in Mouse Brain
Open Access
- 24 February 2010
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 30 (8), 3146-3155
- https://doi.org/10.1523/jneurosci.4140-09.2010
Abstract
Fatty acid binding proteins (FABPs) are essential for energy production and long-chain polyunsaturated fatty acid-related signaling in the brain and other tissues. Of various FABPs, heart-type fatty acid binding protein (H-FABP, FABP3) is highly expressed in neurons of mature brain and plays a role in arachidonic acid incorporation into brain and heart cells. However, the precise function of H-FABP in brain remains unclear. We previously demonstrated that H-FABP is associated with the dopamine D(2) receptor long isoform (D2LR) in vitro. Here, we confirm that H-FABP binds to dopamine D(2) receptor (D2R) in brain extracts and colocalizes immunohistochemically with D2R in the dorsal striatum. We show that H-FABP is highly expressed in acetylcholinergic interneurons and terminals of glutamatergic neurons in the dorsal striatum of mouse brain but absent in dopamine neuron terminals and spines in the same region. H-FABP knock-out (KO) mice showed lower responsiveness to methamphetamine-induced sensitization and enhanced haloperidol-induced catalepsy compared with wild-type mice, indicative of D2R dysfunction. Consistent with the latter, aberrant increased acetylcholine (ACh) release and depolarization-induced glutamate (Glu) release were observed in the dorsal striatum of H-FABP KO mice. Furthermore, phosphorylation of CaMKII (Ca(2+)/calmodulin-dependent protein kinase II) and ERK (extracellular signal-regulated kinase) was significantly increased in the dorsal striatum. We confirmed elevated ERK phosphorylation following quinpirole-mediated D2R stimulation in H-FABP-overexpressing SHSY-5Y human neuroblastoma cells. Together, H-FABP is highly expressed in ACh interneurons and glutamatergic terminals, thereby regulating dopamine D2R function in the striatum.Keywords
This publication has 62 references indexed in Scilit:
- Differential Excitability and Modulation of Striatal Medium Spiny Neuron DendritesJournal of Neuroscience, 2008
- Fabp7 Maps to a Quantitative Trait Locus for a Schizophrenia EndophenotypePLoS Biology, 2007
- Absence of dopamine D2 receptors unmasks an inhibitory control over the brain circuitries activated by cocaineProceedings of the National Academy of Sciences of the United States of America, 2007
- Constitutively active calcineurin mediates delayed neuronal death through Fas‐ligand expression via activation of NFAT and FKHR transcriptional activities in mouse brain ischemiaJournal of Neurochemistry, 2007
- Modulation of D2R-NR2B Interactions in Response to CocaineNeuron, 2006
- Depolarization‐induced suppression of inhibition mediated by endocannabinoids at synapses from fast‐spiking interneurons to medium spiny neurons in the striatumEuropean Journal of Neuroscience, 2006
- Supplementation with a combination of ω-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophreniaSchizophrenia Research, 2003
- Blockade of “reverse tolerance” to cocaine and amphetamine by MK-801Life Sciences, 1989
- Immunohistochemical Localization of Ca2+/Calmodulin‐Dependent Protein Kinase II in Rat Brain and Various TissuesJournal of Neurochemistry, 1988
- Further evidence for the involvement of D2, but not D1 dopamine receptors in dopaminergic control of striatal cholinergic transmissionLife Sciences, 1982