Adenosine A2A receptors in bone marrow-derived cells but not in forebrain neurons are important contributors to 3-nitropropionic acid-induced striatal damage as revealed by cell-type-selective inactivation
| Autor: | Anti Kalda, Joel Linden, Joana E. Coelho, Liqun Yu, Qing-Yuan Huang, Catherine J. Wei, Hai-Ying Shen, Jiang-Fan Chen |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Cell type Receptor Adenosine A2A Transgene Adenosine A2A receptor Bone Marrow Cells Striatum Biology Neuroprotection Mice Prosencephalon medicine Animals Receptor Mice Knockout Neurons General Neuroscience Articles Nitro Compounds Adenosine Corpus Striatum Cell biology Adenosine A2 Receptor Antagonists Mice Inbred C57BL Forebrain Female Propionates Neuroscience medicine.drug |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 26(44) |
| ISSN: | 1529-2401 |
| Popis: | Endogenous adenosine acting at the adenosine A2Areceptor (A2AR) can modify brain injury in a variety of neurological disorder models. However, both A2AR activation and inactivation have been shown to be neuroprotective in different situations, raising the intriguing possibility that A2ARs in distinct cellular elements may have different and even opposing effects. In this study, we developed three novel transgenic models to dissect out cell-type-specific actions of A2ARs on striatal damage by the mitochondrial toxin 3-nitropropionic acid (3-NP). Whereas global inactivation of A2ARs exacerbated 3-NP-induced neurological deficit behaviors and striatal damage, selective inactivation of A2ARs in forebrain neurons (using the Cre/loxP strategy) did not affect neurological deficit or striatal damage after the acute systemic treatment of 3-NP and intrastriatal injection of malonate. However, selective inactivation of A2ARs in bone marrow-derived cells (BMDCs) by transplanting bone marrow cells from global A2AR knock-out (KO) mice into wild-type C57BL/6 mice produced a similar phenotype of global A2AR KO mice, i.e., exacerbation of 3-NP-induced striatal damage. Thus, cell-type-selective inactivation of A2ARs reveals that A2ARs in BMDCs but not in forebrain neurons are an important contributor to striatal damage induced by mitochondrial dysfunction. |
| Databáze: | OpenAIRE |
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