Abstract of Master’s Dissertation
No.1
CourseMPH

NameThesis

Excitatory amino acids, possible causative agents of nodding syndrome in easternTitle

AfricaYasushi Miyauchi

Abstract of Master’s Dissertation

Background :Nodding syndrome (NS) is a progressive disease characterized by nodding symptoms clinicallywith children in eastern Africa. The burden with NS children is heavy not only mentally but
financially for themselves and their family. However, the cause and curative of NS have been
unknown yet.

NS is one type of epilepsy and kainic acid-treated model in experimental

animals is well known for epilepsy model of human. In this study, I examined similarities ofclinical symptoms and histological cerebral changes in kainic acid-treated rat compared withNS pathogenesis. In addition, I considered the possibility kainic acid agonist may be causative
substance for NS.
Objectives :Objectives of this study is to investigate a possibility of excitatory amino acids as causative
agents of NS. Rats were treated with excitatory amino acids and the similarities between theseanimal models and human NS were examined in terms of clinical symptoms andhistopathological changes. In particular, the association of kainic acid with NS was examined.
Methods :After kainic acid and quisqualic acid were administered in rats, clinical signs in rats wereobserved.

Histological lesions were investigated in kainic acid- or quisqualic acid-treated rat

brains and expression of tau protein, GFAP and Iba-1 in kainic acid-treated rat brains wereexamined at 24 hours, 8 days and/or 29 days post-administration.
＊ The abstract, containing background, objectives, methods, results and conclusion should notexceed 300-500words and printed double sided on A4 paper)

Abstract of Master’s Dissertation
No.2
CourseMPH

Name

Yasushi Miyauchi

Further study was conducted by literatures reviewing to find candidate substances that exhibit
kainic acid receptor agonist and additionally, estimation of human toxicity was conducted forthe substance.
Results :Kainic acid induced epileptic symptoms including nodding accompanied by drooling in rats
and bilateral neuronal cell death in the hippocampus, piriform cortex, amygdaloid nucleus andthalamic nucleus of rat brain. In the regions observed neuronal cell death, the overexpressionof phosphorylated tau protein in neurons and the increasing of gliosis with time were seen
immunohistochemically.

These results showed the similarities in clinical symptoms andhistological cerebral lesions with the NS and kainic acid-treated rat epilepsy model.

On theother hand, in this study, quisqualic acid-treated rats shown hypolocomotion, but induced noepileptic symptoms and histological cerebral lesions.
Tricholomic acid, contained in mouldy maize (Ustilago maydis) was suggested to be apotential candidate for kainic acid receptor agonist by searching the previous reports. Inaddition, from estimation study of human toxicity, the human exposure oral dose showing
epileptic symptoms of kainic acid was at 0.2 -2 mg/kg and the intake of tricholomic acid wasestimated at 0.6 mg/kg when the child ingests U. maydis.
Conclusion :In kainic acid-treated rat epilepsy model, similarities in clinical symptoms and histologicalchanges to NS were shown. The possibility that tricholomic acid, one of kainic acid receptor
agonist, shows epileptic symptoms in children is indicated.