Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents

Abstract

Background Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. Methods Young 6-8 weeks old male rats were treated intraperitoneally with either 2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1 μl/g bw saline, daily for 6 weeks. Short-term and long-term memories were assessed using a radial arm maze (RAM) testing paradigm. Results Toxic exposures had an influence on short-term working memory with fewer correct arm entries (F 2, 19 = 4.57 p <0.05), higher working memory errors (WME) (F 2, 19 = 5.09, p <0.05) and longer RAM navigation time (F2, 19 = 3.91, p <0.05) for NaOCN relative to NaCN and saline treatments. The long-term working memory was significantly impaired by cyanide with fewer correct arm entries (F 2, 19 = 7.45, p <0.01) and increased working memory errors (F 2, 19 = 9.35 p <0.05) in NaCN relative to NaOCN or vehicle treated animals. Reference memory was not affected by either cyanide or cyanate. Conclusion Our study findings provide an experimental evidence for the biological plausibility that cassava cyanogens may induce cognition deficits. Differential patterns of memory deficits may reflect the differences in toxicity mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate.

Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet

“…This finding is consistent with previous studies that showed dramatic weight loss in rodents fed SAA-deficient diet or evidence of stunting in children who rely on cassava as staple food (Banea-Mayambu et al, 2000, Stephenson et al, 2010, Tor-Agbidye et al, 1998). Poor gain in body weight in animals treated with NaOCN is consistent with previous findings (Alter et al, 1974, Kimani et al, 2013b). Seizures were observed only in rodents fed SAA and treated with NaCN, and mostly after the first week of the experimentation suggesting that SAA dietary deficiency may modulate the acute toxicity of cyanide.…”

Determinants of cognitive performance in children relying on cyanogenic cassava as staple food

“…Possible mechanisms include nutritional deficiencies and/or direct toxicity effects of cassava cyanogens. For example, low serum proteins may alter cyanide detoxification capabilities resulting in increased production of cyanate, a metabolite capable of inducing both motor and cognition deficits (Ohnishi et al, 1975, Tellez et al, 1979, Tor-Agbidye et al, 1999, Kimani et al, 2013). However, further studies are still needed to rule out a vast array of nutrient deficiencies to explain neurological deficits in konzo-affected areas (Nyaradi et al, 2013).…”

“…Reports on the possible existence of pervasive cognitive deficits among children from konzo-affected areas (Katumbay et al, 2000, Boivin et al, 2013) justify the need for a thorough investigation to determine whether they share common biomarkers and/or mechanisms with the classical paralysis known as konzo. Possible common mechanisms may include the direct effect of cyanide or cyanate, neurotoxic metabolites of linamarin, the main cassava cyanogenic compound (Spencer, 1999, Kimani et al, 2013); the metabolic interference of thiocyanate (SCN), the downstream detoxification product of cyanide, with the uptake of iodine at the thyroid gland level (Erdogan et al, 2001) or glutamergic transmission (Spencer, 1999); a nutritional deficiency in select nutrients (Thilly et al, 1990, Thilly et al, 1993, Adamolekun, 2010); or a combination of the aforementioned factors (Elnour et al, 2000, Erdogan et al, 2001, Bonmarin et al, 2002, Di Filippo et al, 2008, Nyaradi et al, 2013). In this study, we sought to determine whether cognitive deficits observed among children from the most affected area of the DRC (Bonmarin et al, 2002, Boivin et al, 2013) were explained by changes in thyroid function while assessing the role of traditionally known risk factors for konzo e.g.…”

Cyanide and the human brain: perspectives from a model of food (cassava) poisoning

“…Experimental studies suggest that neurocognitive deficits may be caused by cassava cyanogens and/or their metabolites, including cyanate. Whether the motor and cognitive deficits observed in children from konzo areas share the same pathogenic mechanisms has yet to be determined …”

“…Whether the motor and cognitive deficits observed in children from konzo areas share the same pathogenic mechanisms has yet to be determined. 35,[50][51][52]…”