Ultrastructure of synaptic junctions in the cerebellar cortex in experimental valproate encephalopathy and after terminating chronic application of the antiepileptic.
The aim of the study was to analyse in TEM the evolution of changes in structural elements of synaptic junctions of the cerebellar cortex in rats in valproate encephalopathy induced by chronic 12-month administration of sodium valproate - VPA (once daily intragastrically, in a dose of 200 mg/kg b.w.) and after withdrawal of this antiepileptic for 1 and 3 months. After 9 and 12 months of the experiment, synaptic endings of both the symmetrical and asymmetrical synapses in the neuropil of the cerebellar cortex, especially in the molecular layer, showed signs of severe damage (mainly swelling) and even disintegration. They were mostly observed in axodendritic endings and axospinal endings on the dendritic spines of Purkinje cells, being manifested in the presence of large vacuolar structures, electron lucent areas and swollen mitochondria within the cytoplasm. A reduced number of axonal synaptic vesicles (with more type F vesicles preserved) could be seen. One and 3 months after the end of chronic application of VPA, the synaptic junctions did not show morphological exponents of the repair processes. The alterations observed in the synapticjunctions of the cerebellar cortex may suggest disorders in neurotransmission processes, such as exhaustion and damage caused by ischaemia due to damage to the blood-brain barrier induced by VPA and/or its toxic metabolites.
Sobaniec-Lotowska
Maria E
ME
Department of Clinical Pathomorphology, Medical Academy, Białystok, Poland. mariasl@zeus.amb.edu.pl
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D002525:Cerebellar Cortex / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D008297:Male; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D014635:Valproic Acid / Q000009:adverse effects*
D000927:Anticonvulsants; D014635:Valproic Acid