Participation of L-Lactate and Its Receptor HCAR1/GPR81 in Neurovisual Development
During the development of the retina and the nervous system, high levels of energy are required by the axons of retinal ganglion cells (RGCs) to grow towards their brain targets. This energy demand leads to an increase of glycolysis and L-lactate concentrations in the retina. L-lactate is known to b...
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MDPI AG
2021-06-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/7/1640 |
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| author | Samuel Laroche Aurélie Stil Philippe Germain Hosni Cherif Sylvain Chemtob Jean-François Bouchard |
| author_facet | Samuel Laroche Aurélie Stil Philippe Germain Hosni Cherif Sylvain Chemtob Jean-François Bouchard |
| author_sort | Samuel Laroche |
| collection | DOAJ |
| description | During the development of the retina and the nervous system, high levels of energy are required by the axons of retinal ganglion cells (RGCs) to grow towards their brain targets. This energy demand leads to an increase of glycolysis and L-lactate concentrations in the retina. L-lactate is known to be the endogenous ligand of the GPR81 receptor. However, the role of L-lactate and its receptor in the development of the nervous system has not been studied in depth. In the present study, we used immunohistochemistry to show that GPR81 is localized in different retinal layers during development, but is predominantly expressed in the RGC of the adult rodent. Treatment of retinal explants with L-lactate or the exogenous GPR81 agonist 3,5-DHBA altered RGC growth cone (GC) morphology (increasing in size and number of filopodia) and promoted RGC axon growth. These GPR81-mediated modifications of GC morphology and axon growth were mediated by protein kinases A and C, but were absent in explants from <i>gpr81<sup>−/−</sup></i> transgenic mice. Living <i>gpr81<sup>−/−</sup></i> mice showed a decrease in ipsilateral projections of RGCs to the dorsal lateral geniculate nucleus (dLGN). In conclusion, present results suggest that L-lactate and its receptor GPR81 play an important role in the development of the visual nervous system. |
| first_indexed | 2024-03-10T09:55:55Z |
| format | Article |
| id | doaj.art-993978f8d0c64938ab697c93a10ca283 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T09:55:55Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-993978f8d0c64938ab697c93a10ca2832023-11-22T02:19:58ZengMDPI AGCells2073-44092021-06-01107164010.3390/cells10071640Participation of L-Lactate and Its Receptor HCAR1/GPR81 in Neurovisual DevelopmentSamuel Laroche0Aurélie Stil1Philippe Germain2Hosni Cherif3Sylvain Chemtob4Jean-François Bouchard5Neuropharmacology Laboratory, School of Optometry, Université de Montréal, Montreal, QC H3T 1P1, CanadaNeuropharmacology Laboratory, School of Optometry, Université de Montréal, Montreal, QC H3T 1P1, CanadaNeuropharmacology Laboratory, School of Optometry, Université de Montréal, Montreal, QC H3T 1P1, CanadaNeuropharmacology Laboratory, School of Optometry, Université de Montréal, Montreal, QC H3T 1P1, CanadaDepartment of Pediatrics, Research Center-CHU Sainte-Justine, Montreal, QC H3T 1C5, CanadaNeuropharmacology Laboratory, School of Optometry, Université de Montréal, Montreal, QC H3T 1P1, CanadaDuring the development of the retina and the nervous system, high levels of energy are required by the axons of retinal ganglion cells (RGCs) to grow towards their brain targets. This energy demand leads to an increase of glycolysis and L-lactate concentrations in the retina. L-lactate is known to be the endogenous ligand of the GPR81 receptor. However, the role of L-lactate and its receptor in the development of the nervous system has not been studied in depth. In the present study, we used immunohistochemistry to show that GPR81 is localized in different retinal layers during development, but is predominantly expressed in the RGC of the adult rodent. Treatment of retinal explants with L-lactate or the exogenous GPR81 agonist 3,5-DHBA altered RGC growth cone (GC) morphology (increasing in size and number of filopodia) and promoted RGC axon growth. These GPR81-mediated modifications of GC morphology and axon growth were mediated by protein kinases A and C, but were absent in explants from <i>gpr81<sup>−/−</sup></i> transgenic mice. Living <i>gpr81<sup>−/−</sup></i> mice showed a decrease in ipsilateral projections of RGCs to the dorsal lateral geniculate nucleus (dLGN). In conclusion, present results suggest that L-lactate and its receptor GPR81 play an important role in the development of the visual nervous system.https://www.mdpi.com/2073-4409/10/7/1640lactateGPR81HCAR1retinal ganglion cellsgrowth conedLGN |
| spellingShingle | Samuel Laroche Aurélie Stil Philippe Germain Hosni Cherif Sylvain Chemtob Jean-François Bouchard Participation of L-Lactate and Its Receptor HCAR1/GPR81 in Neurovisual Development Cells lactate GPR81 HCAR1 retinal ganglion cells growth cone dLGN |
| title | Participation of L-Lactate and Its Receptor HCAR1/GPR81 in Neurovisual Development |
| title_full | Participation of L-Lactate and Its Receptor HCAR1/GPR81 in Neurovisual Development |
| title_fullStr | Participation of L-Lactate and Its Receptor HCAR1/GPR81 in Neurovisual Development |
| title_full_unstemmed | Participation of L-Lactate and Its Receptor HCAR1/GPR81 in Neurovisual Development |
| title_short | Participation of L-Lactate and Its Receptor HCAR1/GPR81 in Neurovisual Development |
| title_sort | participation of l lactate and its receptor hcar1 gpr81 in neurovisual development |
| topic | lactate GPR81 HCAR1 retinal ganglion cells growth cone dLGN |
| url | https://www.mdpi.com/2073-4409/10/7/1640 |
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