Health Canada, Toxicology Research Division, Banting Bldg, Tunney's Pasture, Ottawa, Ontario, K1A 0L2, Canada.
Mar Drugs. 2010 May 6;8(5):1637-49. doi: 10.3390/md8051637.
Domoic acid produced by marine algae has been shown to cause acute and chronic neurologic sequelae in Californian sea lions following acute or low-dose exposure. Histological findings in affected animals included a degenerative cardiomyopathy that was hypothesized to be caused by over-excitation of the glutamate receptors (GluRs) speculated to be present in the sea lion heart. Thus tissues from five sea lions without lesions associated with domoic acid toxicity and one animal with domoic acid-induced chronic neurologic sequelae and degenerative cardiomyopathy were examined for the presence of GluRs. Immunohistochemistry localized mGluR 2/3, mGluR 5, GluR 2/3 and NMDAR 1 in structures of the conducting system and blood vessels. NMDAR 1 and GluR 2/3 were the most widespread as immunoreactivity was observed within sea lion conducting system structures. PCR analysis, cloning and subsequent sequencing of the seal lion GluRs showed only 80% homology to those from rats, but more than 95% homologous to those from dogs. The cellular distribution and expression of subtypes of GluRs in the sea lion hearts suggests that exposure to domoic acid may induce cardiac damage and functional disturbances.
海洋藻类产生的软骨藻酸已被证明会导致加州海狮在急性或低剂量暴露后出现急性和慢性神经后遗症。受影响动物的组织学发现包括退行性心肌病，据推测这种心肌病是由于谷氨酸受体（GluR）过度兴奋引起的，而这些受体被认为存在于海狮心脏中。因此，检查了五只没有与软骨藻酸毒性相关病变的海狮组织和一只患有软骨藻酸诱导的慢性神经后遗症和退行性心肌病的动物，以检测 GluR 的存在。免疫组织化学将 mGluR 2/3、mGluR 5、GluR 2/3 和 NMDAR 1 定位在传导系统和血管的结构中。NMDAR 1 和 GluR 2/3 的分布最广泛，因为在海狮传导系统结构中观察到了免疫反应。对海豹 GluRs 的 PCR 分析、克隆和随后的测序表明，与大鼠的同源性仅为 80%，但与狗的同源性超过 95%。海狮心脏中 GluR 亚型的细胞分布和表达表明，暴露于软骨藻酸可能会导致心脏损伤和功能障碍。
