Mouse Cerebellar Ataxia Following Acute Diphenylhydantoin Intoxication. VI. Purkinje Cell Cytotoxic Edema
Twenty one days postnatal swiss albino mice received intraperitoneal injection of 5.5 diphenylhydantoin (DPH) at 25 mg/kg daily for 15 days developing progressively gait alterations, changes of behavior and cerebellar ataxia. Cerebellar slices were processed by conventional transmission electron microscopy. Purkinje cell body exhibited fragmented limiting plasma membrane, dilated nuclear envelope, swollen and disassembly of nuclear pores, enlargement of rough and smooth endoplasmic reticulum and notably detachment of membrane associated ribosomes, distorted vacuoles of smooth endoplasmic reticulum, bizarre shaped and swollen mitochondria with dilated mitochondrial cristae, and disrupted limiting lysosomal membrane. Degenerated axosomatic synapses apparently corresponding to basket cell axonal endings were distinguished. Degenerated Purkinje cell axon initial segment exhibited vacuolar degeneration of myelin sheath, dilated axoplasmic tubular bundles, fragmented axolemma, swollen mitochondria, and disassembly of cytoskeletal structures. Some edematous and clear secondary and tertiary dendrites exhibited areas of dilated cisterns of smooth endoplasmic reticulum, clear and dark multivesicular bodies, and coated vesicles. Other dendritic ramifications exhibited an electron dense dendroplasmic. Degenerated and large climbing fiber endings were observed making axodendritic synapses with edematous Purkinje dendrites. These presynaptic endings appeared depleted or containing few synaptic vesicles. These synapses did not exhibit pre- and postsynaptic densities. At the molecular layer, the edematous synaptic varicosities of parallel fibers containing pleomorphic synaptic vesicles and dense extravesicular substance were observed making asymmetric synaptic contacts with swollen Purkinje dendritic spines. These abnormal findings are postulated as pathogenic mechanisms of mouse cerebellar ataxia.
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Document Type: Research Article
Publication date: 01 December 2016
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