Building-Associated Neurological Damage Modeled in Human Cells: A Mechanism of Neurotoxic Effects by Exposure to Mycotoxins in the Indoor Environment

Abstract

Damage to human neurological system cells resulting from exposure to mycotoxins confirms a previously controversial public health threat for occupants of water-damaged buildings. Leading scientific organizations disagree about the ability of inhaled mycotoxins in the indoor environment to cause adverse human health effects. Damage to the neurological system can result from exposure to trichothecene mycotoxins in the indoor environment. This study demonstrates that neurological system cell damage can occur from satratoxin H exposure to neurological cells at exposure levels that can be found in water-damaged buildings contaminated with fungal growth. The constant activation of inflammatory and apoptotic pathways at low levels of exposure in human brain capillary endothelial cells, astrocytes, and neural progenitor cells may amplify devastation to neurological tissues and lead to neurological system cell damage from indirect events triggered by the presence of trichothecenes.

Elimination of damaged mitochondria through mitophagy reduces mitochondrial oxidative stress and increases tolerance to trichothecenes

“…Controlling their accumulation in small grains remains a huge challenge. Trichothecenes cause growth retardation, hemorrhagic lesions, immune dysfunction, and emesis (2,3) and are neurotoxic (4)(5)(6). Trichothecene poisoning causes acute gastroenteritis and has been linked to alimentary toxic aleukia (ATA) and Kashin-Beck disease, an endemic and chronic degenerative osteoarthritis (3).…”

The capability of fungi isolated from moldy dwellings to produce toxins

“…Individual mycotoxins differ in their toxic effects on organisms. Admittedly, they deteriorate the immune system and exhibit carcinogenic, mutagenic, embryotoxic, teratogenic, haemorrhagic, dermatotoxic, cytotoxic, neurotoxic activity, they also impair fertility [19][20][21][22][23]. Toxinogenic activity of individual species of molds is a property that becomes apparent in specific conditions of the substrate's humidity, temperature, availability of nutrients, and the presence of other (competitive) fungi [24,25].…”

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

“…Trichothecene mycotoxins cause multisystemic effects including nervous disorders, cardiovascular alterations, and immunosuppression [236]. A study investigating Satratoxin A exposure demonstrated that the toxin produces neuropathology at levels that occur in water-damaged buildings [237]. Trichothecenes and many other mycotoxins can bind to ribosome subunits generating Bribotoxic stress^which leads to the p38, c-Jun N-terminal kinase (JNK), ERK, and MAPK activation [238][239][240].…”

“…Saratoxin H exposure leads to the activation of MAPKs, JNK p38, and capase-3 together with the predictable development of oxidative stress, increased levels of reactive oxygen species, and the depletion of reduced glutathione [250]. There is evidence that the constant presence of Saratoxin H with subsequent self-amplifying neuroinflammation and chronic immune activation renders an individual more susceptible to the effects of other neurotoxic species in the environment and more susceptible to the presence of such species in the environment thereafter [237,306]. This would be consistent with evidence demonstrating temporal exacerbation of neurotoxicity via microglial priming [21].…”