Role of Chemokine Cxcl12a in Mediating the Stimulatory Effects of Ethanol on Embryonic Development of Subpopulations of Hypocretin/Orexin Neurons and Their Projections
Studies in zebrafish and rats show that embryonic ethanol exposure at low-moderate concentrations stimulates hypothalamic neurons expressing hypocretin/orexin (Hcrt) that promote alcohol consumption, effects possibly involving the chemokine Cxcl12 and its receptor Cxcr4. Our recent studies in zebraf...
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MDPI AG
2023-05-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/10/1399 |
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| author | Nushrat Yasmin Adam D. Collier Abdul R. Abdulai Olga Karatayev Boyi Yu Milisia Fam Sarah F. Leibowitz |
| author_facet | Nushrat Yasmin Adam D. Collier Abdul R. Abdulai Olga Karatayev Boyi Yu Milisia Fam Sarah F. Leibowitz |
| author_sort | Nushrat Yasmin |
| collection | DOAJ |
| description | Studies in zebrafish and rats show that embryonic ethanol exposure at low-moderate concentrations stimulates hypothalamic neurons expressing hypocretin/orexin (Hcrt) that promote alcohol consumption, effects possibly involving the chemokine Cxcl12 and its receptor Cxcr4. Our recent studies in zebrafish of Hcrt neurons in the anterior hypothalamus (AH) demonstrate that ethanol exposure has anatomically specific effects on Hcrt subpopulations, increasing their number in the anterior AH (aAH) but not posterior AH (pAH), and causes the most anterior aAH neurons to become ectopically expressed further anterior in the preoptic area (POA). Using tools of genetic overexpression and knockdown, our goal here was to determine whether Cxcl12a has an important function in mediating the specific effects of ethanol on these Hcrt subpopulations and their projections. The results demonstrate that the overexpression of Cxcl12a has stimulatory effects similar to ethanol on the number of aAH and ectopic POA Hcrt neurons and the long anterior projections from ectopic POA neurons and posterior projections from pAH neurons. They also demonstrate that knockdown of Cxcl12a blocks these effects of ethanol on the Hcrt subpopulations and projections, providing evidence supporting a direct role of this specific chemokine in mediating ethanol’s stimulatory effects on embryonic development of the Hcrt system. |
| first_indexed | 2024-03-11T03:51:15Z |
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| id | doaj.art-f469e0c8d22e4fa9b966437cbce64fe4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T03:51:15Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-f469e0c8d22e4fa9b966437cbce64fe42023-11-18T00:53:03ZengMDPI AGCells2073-44092023-05-011210139910.3390/cells12101399Role of Chemokine Cxcl12a in Mediating the Stimulatory Effects of Ethanol on Embryonic Development of Subpopulations of Hypocretin/Orexin Neurons and Their ProjectionsNushrat Yasmin0Adam D. Collier1Abdul R. Abdulai2Olga Karatayev3Boyi Yu4Milisia Fam5Sarah F. Leibowitz6Laboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY 10065, USALaboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY 10065, USALaboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY 10065, USALaboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY 10065, USALaboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY 10065, USALaboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY 10065, USALaboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY 10065, USAStudies in zebrafish and rats show that embryonic ethanol exposure at low-moderate concentrations stimulates hypothalamic neurons expressing hypocretin/orexin (Hcrt) that promote alcohol consumption, effects possibly involving the chemokine Cxcl12 and its receptor Cxcr4. Our recent studies in zebrafish of Hcrt neurons in the anterior hypothalamus (AH) demonstrate that ethanol exposure has anatomically specific effects on Hcrt subpopulations, increasing their number in the anterior AH (aAH) but not posterior AH (pAH), and causes the most anterior aAH neurons to become ectopically expressed further anterior in the preoptic area (POA). Using tools of genetic overexpression and knockdown, our goal here was to determine whether Cxcl12a has an important function in mediating the specific effects of ethanol on these Hcrt subpopulations and their projections. The results demonstrate that the overexpression of Cxcl12a has stimulatory effects similar to ethanol on the number of aAH and ectopic POA Hcrt neurons and the long anterior projections from ectopic POA neurons and posterior projections from pAH neurons. They also demonstrate that knockdown of Cxcl12a blocks these effects of ethanol on the Hcrt subpopulations and projections, providing evidence supporting a direct role of this specific chemokine in mediating ethanol’s stimulatory effects on embryonic development of the Hcrt system.https://www.mdpi.com/2073-4409/12/10/1399chemokineCxcl12hypocretinorexinethanolprenatal alcohol exposure |
| spellingShingle | Nushrat Yasmin Adam D. Collier Abdul R. Abdulai Olga Karatayev Boyi Yu Milisia Fam Sarah F. Leibowitz Role of Chemokine Cxcl12a in Mediating the Stimulatory Effects of Ethanol on Embryonic Development of Subpopulations of Hypocretin/Orexin Neurons and Their Projections Cells chemokine Cxcl12 hypocretin orexin ethanol prenatal alcohol exposure |
| title | Role of Chemokine Cxcl12a in Mediating the Stimulatory Effects of Ethanol on Embryonic Development of Subpopulations of Hypocretin/Orexin Neurons and Their Projections |
| title_full | Role of Chemokine Cxcl12a in Mediating the Stimulatory Effects of Ethanol on Embryonic Development of Subpopulations of Hypocretin/Orexin Neurons and Their Projections |
| title_fullStr | Role of Chemokine Cxcl12a in Mediating the Stimulatory Effects of Ethanol on Embryonic Development of Subpopulations of Hypocretin/Orexin Neurons and Their Projections |
| title_full_unstemmed | Role of Chemokine Cxcl12a in Mediating the Stimulatory Effects of Ethanol on Embryonic Development of Subpopulations of Hypocretin/Orexin Neurons and Their Projections |
| title_short | Role of Chemokine Cxcl12a in Mediating the Stimulatory Effects of Ethanol on Embryonic Development of Subpopulations of Hypocretin/Orexin Neurons and Their Projections |
| title_sort | role of chemokine cxcl12a in mediating the stimulatory effects of ethanol on embryonic development of subpopulations of hypocretin orexin neurons and their projections |
| topic | chemokine Cxcl12 hypocretin orexin ethanol prenatal alcohol exposure |
| url | https://www.mdpi.com/2073-4409/12/10/1399 |
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