Effect of unilateral perinatal hypoxic-ischemic brain injury in the rat on striatal muscarinic cholinergic receptors and high-affinity choline uptake sites: a quantitative autoradiographic study.
The binding characteristics and distribution of M1 and M2 muscarinic cholinergic receptors and high-affinity choline uptake sites were studied in the striatum of the rat at 3-4 and 9-12 weeks of age after exposure to unilateral perinatal hypoxic-ischemic brain injury. High-affinity choline uptake sites were labeled with [3H]hemicholinium-3, M1 receptors with [3H]pirenzepine, and M2 receptors with [3H]AF-DX 116. Saturation experiments revealed a significant decrease in the maximal binding capacity (Bmax) for [3H]pirenzepine-labeled M1 receptors in the lesioned caudate/putamen complex in immature rats with moderate brain injury, in comparison with controls. In contrast, the Bmax value for [3H]hemicholinium-3-labeled high-affinity choline uptake sites was significantly increased. No changes in dissociation constants (KD) were observed. These changes were most pronounced in the dorsolateral region of striatum. Striatal regional distribution of [3H]AF-DX 116 was not affected. In mature rats, binding of [3H]pirenzepine returned to control values, whereas [3H]hemicholinium binding showed a persistent increase (23%). The increase in [3H]hemicholinium-3 binding, as a specific marker of cholinergic nerve terminals, is consistent with our prior morphologic studies demonstrating relative preservation of cholinergic neurons and neuropil, and supports the concept that striatal cholinergic systems are resistant to hypoxic-ischemic injury.
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
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Kostic
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Przedborski
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Jackson-Lewis
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JL
Cadet
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Burke
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001345:Autoradiography; D001667:Binding, Competitive; D002545:Brain Ischemia / Q000378:metabolism*; D002794:Choline / Q000493:pharmacokinetics*; D003342:Corpus Striatum / Q000378:metabolism*; D006426:Hemicholinium 3 / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D010890:Pirenzepine / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014018:Tissue Distribution
D011976:Receptors, Muscarinic; D006426:Hemicholinium 3; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D002794:Choline