Skip to main content
Log in

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

  • Original Paper
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. 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. 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 (F 2, 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. 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Amizet L, Pruvot G, Remy S, Kfoury M (2011) Occupational cyanide poisoning. BMJ Case Rep. doi:10.1136/bcr.09.2011.4865

    PubMed  Google Scholar 

  • Banea-Mayambu JP, Tylleskar T, Gitebo N, Matadi N, Gebre-Medhin M, Rosling H (1997) Geographical and seasonal association between linamarin and cyanide exposure from cassava and the upper motor neurone disease konzo in former Zaire. Trop Med Int Health 2:1143–1151

    Article  CAS  PubMed  Google Scholar 

  • Banea-Mayambu JP, Tylleskar T, Tylleskar K, Gebre-Medhin M, Rosling H (2000) Dietary cyanide from insufficiently processed cassava and growth retardation in children in the Democratic Republic of Congo (formerly Zaire). Ann Trop Paediatr: Int Child Health 20:34–40

    Article  CAS  Google Scholar 

  • Blanche PA, Yuet WK, David GN (1974) Toxic effects of high-dose cyanate administration in Rodents. Blood 43:69–77

    Google Scholar 

  • Boivin MJ, Okitundu D, Makila-Mabe Bumoko G, Sombo MT, Mumba D, Tylleskar T, Page CF, Tamfum Muyembe JJ, Tshala-Katumbay D (2013) Neuropsychological effects of konzo: a neuromotor disease associated with poorly processed cassava. Paediatr 131:e1231–e1239

    Article  Google Scholar 

  • Carlsson L, Mlingi N, Ronquist G, Rosling H (1995) A specific and sensitive method for determination of linamarin in urine. Nat toxins 3:378–382

    Article  CAS  PubMed  Google Scholar 

  • Chin RG, Calderon Y (2000) Acute cyanide poisoning: a case report. J Emerg Med 18:441–445

    Article  CAS  PubMed  Google Scholar 

  • Cliff J, Nacala D (1997) Long term follow-up of konzo patients. Trans Royal Soc Trop Med 91:447–449

    Article  CAS  Google Scholar 

  • Cliff J, Muquingue H, Nhassico D, Nzwalo H, Bradbury JH (2011) Konzo and continuing cyanide intoxication from cassava in Mozambique. Food Chem Toxicol 49:631–635

    Article  CAS  PubMed  Google Scholar 

  • Crist RD, Grisolia S, Bettis CJ, Grisolia J (1973) Carbamoylation of proteins following administration to rats of carbamoyl phosphate and cyanate and effects of memory. Eur J Biochem 32:109–116

    Google Scholar 

  • Dudchenko PA (2004) An overview of the tasks used to test working memory in rodents. Neurosci and Behav Rev 28:699–709

    Article  Google Scholar 

  • Essers AJA, Alsen P, Rosling H (1992) Insufficient processing of cassava induced intoxications and the paralytic disease konzo in a rural area of Mozambique. Ecol Food and Nutr 27:17–27

    Article  Google Scholar 

  • Fando J, Grisolia S (1974) Carbamylation of brain proteins with cyanate in vitro and in vivo. Eur J Biochem 47:389–396

    Google Scholar 

  • Frey U, Mathies H, Reymann KG (1991) The effect of dopaminergic D1 receptor blockade during tetanization on the expression of long term potentiation in the rat CA1 region in vitro. Neurosci Lett 129:111–116

    Article  CAS  PubMed  Google Scholar 

  • Hayes WT (1967) The 90-dose LD50 and a chronicity factor as measures of toxicity. Toxicol and Appl Pharmacol 11:327–335

    Article  CAS  Google Scholar 

  • Hodges H (1996) Maze procedures: the radial-arm and water maze compared. Cogn Brain Res 3:167–181

    Article  CAS  Google Scholar 

  • Kassa RM, Kasensa NL, Monterroso VH, Kayton RJ, Klimek JE, David LL, Lunganza KR, Kayembe KT, Bentivoglio M, Juliano SL, Tshala-Katumbay DD (2011) On the biomarkers and mechanisms of konzo, a distinct upper motor neuron disease associated with food (cassava) cyanogenic exposure. Food Chem Toxicol 49:571–578

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kuramoto T, Nakanishi S, Ochiai M, Nakagama H, Voigt B, Serikawa T (2012) Origins of albino and hooded rats: implications from molecular genetic analysis across modern laboratory rat strains. PLoS ONE 7:e43059

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mathangi DC, Namasivayam A (2000a) Effect of cassava consumption on open-field behavior and brain neurotransmitters in albino rats. Physiol & Behav 70:89–93

    Article  CAS  Google Scholar 

  • Mathangi DC, Namasivayam A (2000b) Effect of chronic cyanide intoxication on memory in Albino Rats. Food and Chem Toxicol 38:51–55

    Article  CAS  Google Scholar 

  • Mills EM, Gunasekar PG, Pavlakovic G, Isom GE (1996) Cyanide-induced apoptosis and oxidative stress in differentiated PC 12 cells. J Neurochem 67:1039–1046

    Article  CAS  PubMed  Google Scholar 

  • Nunn PB, Lyddiard JR, Christopher Perera KP (2011) Brain glutathione as a target for aetiological factors in neurolathyrism and konzo. Food Chem Toxicol 49:662–667

    Article  CAS  PubMed  Google Scholar 

  • Nzwalo H, Cliff J (2011) Konzo: from poverty, cassava, and cyanogen intake to toxico-nutritional neurological disease. PLoS Negl Trop Dis 5:e1051

    Article  PubMed Central  PubMed  Google Scholar 

  • Okafar PN, Okorowkwo CO, Maduagwu EN (2002) Occupational and dietary exposures of humans to cyanide poisoning from large-scale cassava processing and ingestion of cassava foods. Food and Chem Toxicol 40:1001–1005

    Article  Google Scholar 

  • Olton DS (1985) The radial arm maze as a tool in behavioral pharmacology. Physiol & Behav 40:793–797

    Article  Google Scholar 

  • Olton DS, Samuelson RJ (1976) Remembrance of placed passed: spatial memory in rats. J Exp Psychol: Anim Behav Proc 2:97–116

    Google Scholar 

  • Rosling H (1994) Measuring effects in humans of dietary cyanide exposure from cassava. Acta Hortic 375:271–283

    CAS  Google Scholar 

  • Rosling H, Tylleskar T (1995) Konzo an epidemic upper motor neuron disease associated to cassava and agro-ecological collapse in Africa. In: Tropical Neurology. Sauders, London, pp 353–364

  • Rosling H, Gessain A, de Thé G, Ebondo N, Banea M, Bikangi N, Kinjanja K, Nunga M (1988) Tropical and epidemic spastic paraparesis are different. Lancet 8596:1222–1223

    Article  Google Scholar 

  • Speiser Z, Amitz-Zonder J, Ashkenazi R, Gitter S, Cohen S (1990) Central catecholaminergic dysfunction and behavioural disorders following hypoxia in adult rats. Behav and Brain Res 37:19–27

    Article  CAS  Google Scholar 

  • Spencer PS (1999) Food toxins, AMPA receptors, and motor neuron diseases. Drug Metab Rev 31:561–587

    Article  CAS  PubMed  Google Scholar 

  • Swenne I, Eriksson UJ, Christoffersson R, Kagedal B, Lundquist P, Nilsson L, Tylleskar T, Rosling H (1996) Cyanide detoxification in rats exposed to acetonitrile and fed a low protein diet. Fundam Appl Toxicol 32:66–71

    Article  CAS  PubMed  Google Scholar 

  • Sykes AH (1981) Early studies on the toxicology of cyanide. In: Vennesland B, Conn EE, Knowles CJ, Westley J, Wissing F (eds) Cyanide in biology. Academic Press, London, pp 1–9

  • Tewe OO, Maner JH (1982) Cyanide protein and iodine interaction in the physiology and metabolism of rats. Food Chem 9:195–204

    Article  CAS  Google Scholar 

  • Tor-Agbidye J, Palmer VS, Lasarev MR, Craig AM, Blythe LL, Sabri MI, Spencer PS (1999) Bioactivation of cyanide to cyanate in sulfur amino acid deficiency: relevance to neurological disease in humans subsisting on cassava. Toxicol Sci 50:228–235

    Article  CAS  PubMed  Google Scholar 

  • Tshala-Katumbay D, Lukusa VM, Eeg-Olofsson K (2000) EEG findings in Konzo: a spastic para/tetraparesis of acute onset. Clin Electroencephalogr 31:196–200

    Google Scholar 

  • Tshala-Katumbay D, Eeg-Olofsson K, Tylleskar T, Kazadi-Kayembe T (2001) Impairments, disabilities and handicap pattern in konzo - a non-progressive spastic para/tetraparesis of acute onset. Disabil and Rehabil 23:731–736

    Article  CAS  Google Scholar 

  • Tylleskär T, Banea M, Bikangi N, Fresco L, Persson LÅ, Rosling H (1991) Epidemiological evidence from Zaire for a dietary aetiology of konzo, an upper motor neuron disease. Bull World Health Organ 69:581–590

    PubMed Central  PubMed  Google Scholar 

  • Way JL (1984) Cyanide intoxication and its mechanism of antagonism. Ann Rev Pharmacol Toxicol 24:451–481

    Google Scholar 

  • Wenk G, Sweeney J, Hughey D, Carson J, Olton D (1986) Choline acetyltransferase inhibition does not impair radial maze performance in rats. Pharmacol, Biochem Behav 25:521–526

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Partially supported by the International Society for Neurochemistry/Committee for Aid and Education in Neurochemistry and the NIEHS and FIC grant R21ES017225 and R01ES019841 from the National Institutes of Health, Bethesda, MD.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Kimani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kimani, S., Sinei, K., Bukachi, F. et al. Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents. Metab Brain Dis 29, 105–112 (2014). https://doi.org/10.1007/s11011-013-9459-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-013-9459-2

Keywords

Navigation