Open Access

ARTICLE

Mouse cerebellar Purkinje cell damage induced by diphenylhydantoin acute intoxication

by Orlando J. CASTEJÓN

Biological Research Institute and Faculty of Medicine, Zulia University, Maracaibo, Venezuela.

*Address correspondence to:Orlando J. Castejón,

BIOCELL 2015, 39(2-3), 33-40. https://doi.org/10.32604/biocell.2015.39.033

Abstract

Twenty one days old Swiss albino mice that received diphenylhydantoin (25 mg/kg, i.p., daily for 15 days) progressively developed gait alterations, changes of behavior and cerebellar ataxia. Cerebellar slices were processed by conventional transmission electron microscopy. The body of Purkinje cells exhibited fragmented limiting plasma membranes, dilated nuclear envelopes, swelling and disassembly of nuclear pores, enlargement of rough and smooth endoplasmic reticulum and a notable detachment of membrane associated ribosomes, together with distorted vacuoles of smooth endoplasmic reticulum, bizarre shaped and swollen mitochondria with dilated cristae, as well as disrupted limiting lysosomal membranes. Degenerated axosomatic synapses apparently corresponding to basket cell axonal endings were recognized. Degenerated Purkinje cell axon initial segments exhibited vacuolar degeneration of myelin sheath, dilated axoplasmic tubular bundles, fragmented axonal membranes, 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 dendroplasm. 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 findings are postulated as pathogenic mechanisms of mouse cerebellar ataxia.

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