The results of the two experimental studies done on neuronal tissue culture cells clearly support the observations on damage to the olfactory mucosa, olfactory neurons, tract and bulbs observed in the above mouse models.
Ochratoxin A (OTA)
OTA has been demonstrated to be teratogenic in animal studies. Oral dosing of pregnant hamsters at concentration from 2.0 to 20 mg/kg caused malformations of the brain and head of fetuses as follows: mirognathia, hydrocephalus, short tail, syndactyly , cleft lip and heart defects (Hood et al, 1976).
An oral dose of 2.75 mg/kg bw to pregnant Wistar rats resulted in maternal toxicity and fetal malformations as follows: external and internal hydrocephaly, incomplete closure of skull, omphalocele, microphthalmia, enlarged renal pelvis and renal hypoplasia. Skeletal defects include the skull bones, sternebrae, vertebrae and ribs.
Patil et al, 2006. Intraperitoneal injection of 2-4 mg/kg bw of pregnant mice caused craniofacial malformations. Ochratoxin A exacerbated the fetal effects of T-1 toxin (Hood et al, 1978).
Hood RD, Kuczuk MH, Szczech GM. 1978. Effects in mice of simultaneous prenatal exposure to ochratoxin A and T-2 toxin. Teratology 17:25-9.
Hood RD, Naughton MJ, Hayes AW. 1976. Prenatal effects of ochratoxin A in hamsters. Toxicol 13:11-4.
Patil RD, Dwivedi P, Sharma AK. 2006. Critical period and minimum single oral dose of ochratoxin A for inducing developmental toxicity in pregnant Wistar rats. Reprod Toxicol 22:679-87.
Acute neurotoxic effects of OTA in Swiss mice has been examined (Sava et al, 2006). Intraperitoneal injection of 3.5 mg/kg bw (10 % of LD50 of 3.95 mg/kg) caused multiple indications of cerebral damage. The following areas of brain were dissected and tested for presence of damage: cerebellum (CB); pons/medulla (PM; Midbrain (MB); caudate/putamen; Hippocampus (HP); and cerebral cortex (CX). All regions of the brain had toxic findings that included inhibition of repair of oxidative DNA repair; elevated lipid peroxidation products, upregulation of superoxide dismustase, and a decrease in dopamine and its metabolites in the CD region. Thus, OTA caused acute depletion of striatal (CD) dopamine on a background of increased oxidative stress and transient inhibition of oxidative DNA repair.
In a subsequent experiment, OTA caused a time and dose dependent decrease in viability of both proliferating and differentiating neural stem/progenitor cells isolated from mouse brain (Sava et al, 2007). This resulted from oxidative damage as shown in the previous study. The authors conclude these results lead to speculation that OTA exposure may contribute to impaired hippocampal neurogenesis in vivo, resulting in depression and memory deficits, conditions reported to be linked to mycotoxin exposure in humans.
Sava V, Reunova 0, Velasquez A, Harbison R, Sanchez-Ramos J. 2006. Acute neurotoxic effects of fungal metabolite ochratoxin A. Neurotoxicol 27:82-92.
Sava S, Velasqquez A, Song S, Sancehz-Ramos J. 2007. Adult hippocampal neural/progenitor cells in vitro are vulnerable to the mycotoxins ochratoxin A. Toxicol Sci 98:2007.
Aflatoxin B1 (AFB1)
Toxic encephalopathy was originally described in children with Reye's syndrome associated with consumption of Aflatoxin B1 and/or salicylates (Trauner, 1984: Dvorackova et al, 1977) and subsequently in cases of aflatoxicosis in canines and Chinese children (Dereszynski etl, 2008; Lye et al, 1995). Thus, these observations suggest that Aflatoxins may be neurotoxic. The peer-reviewed papers briefly reviewed herein are highly suggestive that these mycotoxins are toxic to various aspects of brain chemistry and, thus, brain function.
Intranasal instillation of AFB1 in rats results in damage to the nasal mucosa resembling that seen with Satratoxin G and Roridin A. The pathology included disorganized undulating olfactory epithelium, with injured neuronal and sustentacular cells.
Selective destruction of mucous cells also occurred.
Radioactively (tritium) labeled AFB1 was present in the olfactory tract and olfactory bulbs. (Larsson and Tjalve, 2000).
Furthermore, depletion of glutathione stores leads to distribution of AFB1 to other organ systems, including the upper and lower respiratory tract in fetal, infant and adult mice (Larsson and Tjalve, 1992).
If you wish to do an entrez pubmed search of Larsson and Aflatoxin B1, you will find similar results on animals other than mice and rats.
Cytochrome P450 enzymes and other enzymes that activate xenobiotics as well as AFB1 are present in the nasal mucosa and bronchial cells (Van Vleet RT, Mace K, Coulombe RA. 2002; Zhang et al, 2005).
AFB1 also alters the levels of various biogenic amines (neurotransmitters) and their precursors in rat and mouse brains. These include a decrease in dopamine, serotonin and alterations in the levels of the precursors tyrosine and tryptophan (Weekley et al, 1989; Coulomre and Sharma, 1985; Jayasekara e tal, 1989; Kimbrough et al, 1992). Deficiencies in both of these neurotransmitter lead to neurological symptoms such as neurocognitive decline and alteration of sleep cycle.
Columre RA, Sharma RP. 1985. Effect of repeated exposure of aflatoxin B1 on brain biogenic amines and metabolites in the rat. Toxicol Appl Pharmacol 80:496-501.
Dereszynski DM, Center SA, Randolph JF, Brooks MD, et al. 2008. Clinical and clinicopathologic features of dogs that consumed food borne hepatoxic aflatoxins: 72 cases (2005-2006). J Am Vet Med Assoc 232:1329-37.
Dvorakova I, Kusak V, Vessely D, Vessela J, Nesidal P. 1977. Aflatoxin and encephalopathy with fatty degeneration of viscera. (Reye) Ann Nutr Aliment 31:977-89.
Jayasekra S, Drown DB, Coulombe RA, Sharma RP. 1989. Alteration of biogenic amines in mouse brain regions by alkylating agents. Effects of aflatoxin B1 on brain monoamines concentrations and activities of metablozing enzymes. Arch Environ Contam Toxicol 18:396-403.
Kimbrough TD, Llewellyn GC, Weekley LB. 1992. The effect of aflatoxin B1 on serotonin metabolism: Response to a tryptophan load. Metab Brain Dis. 7:175-82.
Larsson P, Tjalve H. 1992. Binding of aflatoxin B1 metabolites in extrahepatic tissues in fetal and infant mice and in adult mice with depleted glutathione levels. Cancer Res 52:1267-77.
Larsson P, Tjalve H. 2000. Intranasal instillation of Aflatoxin B1 in rats: Bioactivation in the nasal mucosa and neuronal transport to the olfactory bulb. Toxicol Sci 55:383-91.
Lye MS,. Ghazali AA, Mohan J, Nair WN. 1995. An outbreak of acute hepatic encephalopathy due to severe aflatoxicosis in Malaysia. Am J Trop Med Hyg 53:68-72.
Van Vleet TR, Mace K, Coulombe RA. Comparative aflatoxin B1 and cyotoxicity in human bronchial cells expressing cytochromes P450 1A2 and 3A4. Cander Res, 62:105-12.
Weekley LB, O'Rear CE, Kimbrough TD, Lewellyn GC. 1989. Differential changes in rat brain tryptophan, serotonin and tyrosine levels following acute aflatoxins B1 treatment. Toxicol Lett 47:173-7.
Zhang X, Shang QY, Liu C, Xu T, Weng Y, et al. 2005. Expression of cytochrome P450 and other biotransformation genes in fetal and adult human nasal mucosa. Drub Metab Dispos 33:1423-8.