The effect of physiological stress as a risk factor of neurolathyrism

Kimino Minagawa, Toshio Kumai, Shinichi Yamada, Ayano Suzuki, Kuniko Kusama-Eguchi
2018 Proceedings for Annual Meeting of The Japanese Pharmacological Society  
Neurolathyrism is a motor neuron disease with hind-leg paraparesis caused by the deterioration in upper and lower motor neurons. The disease is caused by the overconsumption of grass pea a draught-tolerant food, which has long been a staple food in some countries in Africa and Eurasian subcontinent. Grass pea contains a neurotoxic amino acid, β-N-oxalyl-Ldiaminopropionic acid (ODAP) an AMPA-type glutamatergic receptor agonist. Historically the outbreaks of NL have took place in the
more » ... in the concentration camp during the world war II, at the time of Spanish civil war and at severe food shortages such as Ethiopian famine around 1997-1998 the biggest incidence being 66% in the first case. We have reported a rodent model of NL by treating rat pups repeatedly with ODAP after loading them with mild stress. The incidence was as much as 20-30% was obtained only in the early period after birth of growing and the stress condition. Considering the enhanced social stress such as prisonization, war and famine, associated stress responses should be the important factors to cause NL-like motor symptoms. The hypothalamo-pituitary-adrenal (HPA) axis is a major responder in mammals to physiological stress. To investigate whether the response of the HPA axis is involved in NL pathology, we examined the expression of adrenocorticotropic hormone (ACTH), corticosterone (CORT). We measured plasma ACTH and serum CORT by enzyme immunoassay (EIA) of postnatal day 2 rats, the most frequent period of onset of hind-leg paraparesis. The plasma ACTH and serum CORT concentrations were increased by 2.5-fold in maternal separation rats respectively as compared with naive rats. Glucocorticoid receptor (GR) mediates stress response of glucocorticoid. We measured GR mRNA using real-time RT-PCR. Our preliminary data showed a slight decrease in the expression of GR mRNA in the spinal cord of the hind-leg paraparetic rat compared to the non-paraparetic ODAP-treated rat. Furthermore, we demonstrated that pretreatment of dexamethasone, a synthetic glucocorticoid, enhanced the incidence of paraparesis by ODAP-treatment. These results suggested that increased HPA-axis is the important factor of the motor neuron toxicity of ODAP through the glucocorticoid receptor-mediated mechanism. Poster session WCP2018
doi:10.1254/jpssuppl.wcp2018.0_po2-1-85 fatcat:qkjyyhii2vczpprl5prjvnzw4u