Fungal Food Toxins Can Breach the Brain: Review Maps How Mycotoxins Damage the Nervous System

A sweeping review of the scientific literature has pulled together the growing evidence that mycotoxins, the toxic chemical weapons produced by fungi that contaminate a large share of the world’s food supply, can reach the brain and inflict damage on neurons and glial cells through a strikingly diverse set of molecular mechanisms. The scoping review, published in Discover Toxicology by a team led by Wilfred Angie Abia of the University of Yaounde 1 in Cameroon, synthesizes findings from in vitro and in vivo studies on six of the most common food-borne mycotoxins: aflatoxin B1, ochratoxin A, fumonisin B1, zearalenone, T-2 toxin, and deoxynivalenol. The authors conclude that these compounds pose a significant risk to the central nervous system, with potential long-term consequences for cognition, behaviour, and neurological health, particularly in children.

The scale of exposure is far from trivial. According to the Food and Agriculture Organization of the United Nations, roughly 25 percent of global crops are contaminated with mycotoxins, although the review notes that the true figure for detectable levels may exceed 60 percent. These fungal metabolites can invade food and feed at every stage of the food chain, from field to storage, and climate change together with poor storage conditions, including elevated water activity, temperature, and relative humidity, is expected to worsen fungal colonization and toxin production. Humans encounter mycotoxins through the respiratory system, the skin, and the gastrointestinal tract, with the diet representing the primary route of long-term exposure. Cereals such as maize are frequent carriers, while nuts are especially vulnerable to aflatoxins.

What makes the new synthesis particularly compelling is the accumulating evidence that several of these toxins can cross the blood-brain barrier, the highly selective endothelial fence that normally shields the brain from circulating hazards. Once inside, they accumulate in neural tissue and attack both neurons and glial cells. The review identifies a shared arsenal of damaging mechanisms: disruption of neuronal signalling pathways, DNA damage, epigenetic modifications, impaired neurogenesis, oxidative stress, dysregulated autophagy, interference with neurotransmitter systems, mitochondrial dysfunction, and neuroinflammation. The severity of the resulting neurological outcomes depends on the dose, duration, and timing of exposure, and has been linked to cognitive impairments, learning difficulties, behavioural abnormalities, and neurodegenerative and neurodevelopmental disorders, including Alzheimer’s and Parkinson’s diseases.

Ochratoxin A emerges as one of the most thoroughly characterized brain-seeking toxins. In rat brain cell cultures, OTA disrupts the neuronal cytoskeleton, reducing heavy neurofilament expression and altering oligodendrocyte maturation by decreasing myelin basic protein and myelin oligodendrocyte glycoprotein, structural changes that threaten neuronal function and myelination. Work on the mouse subventricular zone, a key neurogenic niche, showed that OTA impairs cell viability, proliferation, and differentiation in a dose-dependent manner, while chronic exposure damaged hippocampal cells in adult mice, a finding that may underpin learning and memory deficits. In three-dimensional brain cultures, OTA disrupted the cytoskeletons of neurons and astrocytes and triggered neuroinflammation. In human astrocytes, the toxin reduces proliferation, induces cell cycle arrest, and drives apoptosis through loss of mitochondrial membrane potential, while activating the JNK1/2 and p38 stress kinases, likely via disrupted calcium signalling. In microglia, OTA provokes release of the proinflammatory cytokines IL-1β, IL-18, and CXCL8, and in zebrafish it causes locomotor impairment alongside altered oxidative stress markers such as glutathione peroxidase and glutathione-S-transferase.

Zearalenone, an oestrogenic Fusarium toxin, attacks neurons through a different route. In human neuroblastoma SH-SY5Y cells it generates reactive oxygen species, lipid peroxidation, loss of mitochondrial membrane potential, and DNA double-strand breaks, with the metabolites α-zearalenol and β-zearalenol similarly disrupting the cell cycle. ZEN also activates the mitogen-activated protein kinase signalling cascade, a conserved pathway governing proliferation, survival, and apoptosis, with ROS acting as signalling intermediates that can tip cells toward programmed death. In the nematode Caenorhabditis elegans, long-term exposure induced mitochondrial fragmentation, upregulated fission and apoptosis genes, and suppressed the DAF-16/FOXO transcription factor, a central regulator of ageing and longevity, producing an ageing-related decline. In zebrafish larvae, ZEN inhibited muscle and neural development through caspase-8-dependent apoptosis and altered expression of neuronal markers including tyrosine hydroxylase and brain-derived neurotrophic factor, confirming its capacity to derail normal neuronal function.

Fumonisin B1 takes aim at cellular metabolism itself. In rat primary astrocytes and SH-SY5Y cells, FB1 inhibits mitochondrial complex I, depressing cellular respiration, depolarizing the mitochondrial membrane, spurring ROS production, and deregulating calcium signalling. Its signature lesion, however, lies in sphingolipid metabolism: by inhibiting ceramide synthases, FB1 blocks ceramide formation, causing sphinganine and sphingosine to accumulate while complex sphingolipids dwindle, a disruption tied to apoptosis, cell cycle derangement, and membrane dysfunction. This mechanism links fumonisins to equine leukoencephalomalacia and, in humans, to neural tube defects. FB1 also renders neurons more vulnerable to glutamate-induced excitotoxicity, alters GABAergic and serotonergic systems in C. elegans with resulting behavioural deficits, and suppresses immune function by impairing dendritic cell maturation and cytokine secretion, compounding the neurological threat with immunological vulnerability.

Aflatoxin B1, described in the review as the most potent natural carcinogen known, is equally formidable in the brain. In primary microglial cells it triggers lactate dehydrogenase leakage, DNA damage markers, nuclear lysis, and release of IL-1β, IL-18, and TNF-α, activating the NLRP3 inflammasome and gasdermin D-mediated pyroptosis, an inflammatory form of cell death that fuels neuroinflammation and neuronal loss. In astrocytes it causes cell cycle arrest and mitochondrial apoptosis involving Bax, Bak, and cytochrome C, while in zebrafish embryos it inhibits Na+/K+-ATPase in brain synaptosomes, producing hyperlocomotion and suppressing neurogenesis genes. Repeated administration in rats degenerates central and peripheral nerve fibres and myelin sheaths, alters biogenic amines governing cognition and memory, and disrupts hypothalamic neuropeptide balance. The toxin’s liver-derived reactive epoxide metabolite, AFB1-8,9-epoxide, is central to this oxidative assault on neural tissue.

The trichothecene T-2 toxin and deoxynivalenol round out the roster. T-2, considered the most toxic trichothecene, dismantles the cellular redox balance, overwhelming antioxidant defences and damaging lipids, proteins, and DNA; it impairs mitochondria in mouse primary neurons and N2a cells, activates caspases 8, 9, and 3 through both intrinsic and extrinsic apoptotic routes, and suppresses the Nrf2/HO-1 antioxidant defence axis. Critically, T-2 also breaches the blood-brain barrier itself, via oxidative stress and activation of matrix metalloproteinase-9, which degrades the extracellular matrix proteins collagen, laminin, and fibronectin that hold endothelial tight junctions together, inviting immune cells into the brain. DON, meanwhile, drives mitochondrial apoptosis in PC12 and hippocampal cells through Bcl-2 family mediators and p53, induces G1 cell cycle arrest in glial and hippocampal cells, shrinks dendritic arborization, shifts neurotransmitter levels, with norepinephrine and serotonin rising as dopamine and GABA fall, and triggers autophagy through the PI3K/Akt/mTOR pathway.

The review’s authors stress that, compared with other organ systems, research on mycotoxin effects on the brain remains limited, and they call for intensified study of the toxin-neuron interface to identify new drug targets within the central nervous system. They argue that protecting the public demands a comprehensive strategy spanning regulatory measures, improved agricultural and manufacturing practices, public awareness, and sustained research collaboration, alongside urgent risk assessment and stricter legislation covering both established and emerging mycotoxins in daily diets. As contamination pressures grow with a changing climate, the message of this synthesis is stark: the fungi that colonize the world’s staple crops may be quietly shaping brain health on a global scale, and the scientific community is only beginning to map the full extent of the damage.

Subject of Research: Neurotoxicity mechanisms of food-borne mycotoxins

Article Title: A scoping review on mycotoxin-induced neurotoxicity

Article References: Abia, W. A., Foupouapouognigni, Y., Nfombouot, H. P. N., Ngoungoure, L. V. N., Ntungwe, E. N., Salah-Abbès, J. B., & Tchana, A. N. (2025). A scoping review on mycotoxin-induced neurotoxicity. Discover Toxicology, 2(1), Article 1. https://doi.org/10.1007/s44339-024-00013-7

Image Credits: AI Generated

DOI: 10.1007/s44339-024-00013-7

Keywords: mycotoxins, neurotoxicity, blood-brain barrier, aflatoxin B1, ochratoxin A, fumonisin B1, zearalenone, T-2 toxin, deoxynivalenol, oxidative stress, neuroinflammation, food safety