Ravi Madhu, Lacson Atilano, Pybus Margo, Ball Mark C
Animal Health and Assurance, Alberta Agriculture, Forestry and Rural Economic Development, Edmonton, AB T6H 4P2, Canada.
Department Laboratory Medicine and Pathology at Alberta Precision Laboratories, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Animals (Basel). 2022 Jun 25;12(13):1633. doi: 10.3390/ani12131633.
Lafora disease is an autosomal recessive glycogen-storage disorder resulting from an accumulation of toxic polyglucosan bodies (PGBs) in the central nervous system, which causes behavioral and neurologic symptoms in humans and other animals. In this case study, brains collected from two young adult free-ranging moose () cows that were seemingly blind and found walking in circles were examined by light and electron microscopy. Microscopic analysis of the hippocampus of the brain revealed inclusion bodies resembling PGBs in the neuronal perikaryon, neuronal processes, and neuropil. These round inclusions measuring up to 30 microns in diameter were predominantly confined to the hippocampus region of the brain in both animals. The inclusions tested α-synuclein-negative by immunohistochemistry, α-synuclein-positive with PAS, GMS, and Bielschowsky's staining; and diastase-resistant with central basophilic cores and faintly radiating peripheral lines. Ultrastructural examination of the affected areas of the hippocampus showed non-membrane-bound aggregates of asymmetrically branching filaments that bifurcated regularly, consistent with PGBs in both animals. Additionally, α-synuclein immunopositivity was noted in the different regions of the hippocampus with accumulations of small granules ultrastructurally distinct from PGBs and morphologically compatible with alpha-synucleinopathy (Lewy body). The apparent blindness found in these moose could be related to an injury associated with secondary bacterial invasion; however, an accumulation of neurotoxicants (PGBs and α-synuclein) in retinal ganglions cells could also be the cause. This is the first report demonstrating Lafora disease with concurrent alpha-synucleinopathy (Lewy body neuropathy) in a non-domesticated animal.
拉福拉病是一种常染色体隐性糖原贮积症，由有毒性的聚葡萄糖体（PGBs）在中枢神经系统中蓄积所致，可在人类和其他动物身上引发行为和神经症状。在本病例研究中，对两头看似失明且转圈行走的成年自由放养驼鹿母鹿的大脑进行了光镜和电镜检查。对大脑海马体的显微镜分析显示，在神经元胞体、神经突和神经纤维网中存在类似PGBs的包涵体。这些圆形包涵体直径达30微米，主要局限于两只动物大脑的海马体区域。免疫组化检测显示这些包涵体α-突触核蛋白呈阴性，PAS、GMS和 Bielschowsky染色显示α-突触核蛋白呈阳性；对淀粉酶有抗性，中央有嗜碱性核心，外周有微弱放射状线条。对海马体病变区域的超微结构检查显示，存在不对称分支细丝的无膜结合聚集体，这些细丝规则分叉，与两只动物体内的PGBs一致。此外，在海马体的不同区域发现了α-突触核蛋白免疫阳性，超微结构显示有小颗粒聚集，与PGBs不同，形态上与α-突触核蛋白病（路易体病）相符。这些驼鹿出现的明显失明可能与继发细菌感染相关的损伤有关；然而，视网膜神经节细胞中神经毒物（PGBs和α-突触核蛋白）的蓄积也可能是原因。这是首次报道在非家养动物中出现拉福拉病并发α-突触核蛋白病（路易体神经病）的情况。
