This page lists medical journal articles discussing neurological issues associated with Stachybotrys exposures.
The Health Effects of Stachybotrys Chartarum page of the Paradigm Change site provides further information on the effects of this toxic mold.
Torres G, Hoehmann CL, Cuoco JA, Hitscherich K, Pavia C, Hadjiargyrou M, Leheste JR. Ketamine intervention limits pathogen expansion in vitro. Pathog Dis. 2018 Mar 1;76(2). PMID: 29365093
Ketamine is one of several clinically important drugs whose therapeutic efficacy is due in part to their ability to act upon ion channels prevalent in nearly all biological systems. In studying eukaryotic and prokaryotic organisms in vitro, we show that ketamine short-circuits the growth and spatial expansion of three microorganisms, Stachybotrys chartarum, Staphylococcus epidermidis and Borrelia burgdorferi, at doses efficient at reducing depression-like behaviors in mouse models of clinical depression. Although our findings do not reveal the mechanism(s) by which ketamine mediates its antifungal and antibacterial effects, we hypothesize that a function of L-glutamate signal transduction is associated with the ability of ketamine to limit pathogen expansion. In general, our findings illustrate the functional similarities between fungal, bacterial and human ion channels, and suggest that ketamine or its metabolites not only act in neurons, as previously thought, but also in microbial communities colonizing human body surfaces.
F. Harding, C. L. Pytte, K. Page, R. Persaud, R. DeStafano, T. Roa, E. Normand, M. Nagai, E. Williams, L. Blachorsky. Mold inhalation, brain inflammation, and behavioral dysfunction. Presentation, Neuroscience 2014 Conference. November 15, 2014.
The researchers compared mice treated with 1) intact, toxic Stachybotrys spores (IN), 2) extracted Stachybotrys spores that had their toxins removed and proteins denatured leaving skeletal elements (EX), or 3) vehicle (VEH). Mice were treated with relatively low spore doses 3X per week. Inhalation of both spore types caused striking deficits in contextual memory. Inhalation of EX spores also caused deficits in spatial memory. Inhalation of EX spores significantly increased anxiety, while inhalation of IN spores significantly increased fear of an auditory cue previously paired with a mild footshock. These changes in behavior were correlated with measures of increased brain inflammation. Deficits in contextual memory were correlated with numbers of amoeboid microglia and microglial size in the dorsomedial dentate gyrus. Spore inhalation increased numbers of cells in the hippocampus expressing the proinflammatory cytokine interleukin-1beta (IL-1beta). Increased numbers of cells expressing IL-1beta in hippocampal CA1 were positively correlated with spatial memory deficits and increased fear. Mold exposure also affected two of three stages of neurogenesis. Inhalation of EX spores decreased numbers of immature new neurons in the dorsomedial hippocampus expressing doublecortin, while IN treatment decreased numbers of adult-born BrdU-labeled neurons that matured and expressed NeuN.
Jia C, Hayoz S, Hutch CR, Iqbal TR, Pooley AE, Hegg CC. An IP3R3- and NPY-expressing microvillous cell mediates tissue homeostasis and regeneration in the mouse olfactory epithelium. PloS one. 2013;8. PMID: 23516531
In the olfactory system, the IP3 receptor subtype 3 (IP3R3) is expressed exclusively in a microvillous cell subtype that is the predominant cell expressing neurotrophic factor neuropeptide Y (NPY). We hypothesized that IP3R3-expressing microvillous cells secrete sufficient NPY needed for both the continual maintenance of the neuronal population and for neuroregeneration following injury. We addressed this question by assessing the release of NPY and the regenerative capabilities of wild type, IP3R3(+/-), and IP3R3(-/-) mice. Although the number of mature neurons and the in vivo rate of proliferation were not altered, the proliferative response to the olfactotoxicant satratoxin G and olfactory bulb ablation injury was compromised in the olfactory epithelium of IP3R3(-/-) mice.
Carey SA, Plopper CG, Hyde DM, Islam Z, Pestka JJ, Harkema JR. Satratoxin-G from the black mold Stachybotrys chartarum induces rhinitis and apoptosis of olfactory sensory neurons in the nasal airways of rhesus monkeys. Toxicologic pathology. 2012;40:887–898. PMID: 22552393
The researchers developed a model of Satratoxin G (SG) exposure in monkeys, whose nasal airways resemble those of humans. SG induced acute rhinitis, atrophy of the olfactory epithelium (OE), and apoptosis of OSNs in both groups.
Jia C, Sangsiri S, Belock B, Iqbal TR, Pestka JJ, Hegg CC. ATP mediates neuroprotective and neuroproliferative effects in mouse olfactory epithelium following exposure to satratoxin G in vitro and in vivo. Toxicological sciences : an official journal of the Society of Toxicology. 2011;124:169–178. PMID: 21865290
Intranasal aspiration of satratoxin G (SG), a mycotoxin produced by the black mold Stachybotrys chartarum, selectively induces apoptosis in olfactory sensory neurons (OSNs) in mouse olfactory epithelium (OE) through unknown mechanisms. Here, the authors show a dose-dependent induction of apoptosis 24 h post-SG exposure in vitro. The data indicate that ATP is neuroprotective against Satratoxin G-induced OE toxicity.
Karunasena E, Larrañaga MD, Simoni JS, Douglas DR, Straus DC. Building-associated neurological damage modeled in human cells: a mechanism of neurotoxic effects by exposure to mycotoxins in the indoor environment. Mycopathologia. 2010;170:377–390. PMID: 20549560
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.
Islam Z, Shinozuka J, Harkema JR, Pestka JJ. Purification and comparative neurotoxicity of the trichothecenes satratoxin G and roridin L2 from Stachybotrys chartarum. Journal of toxicology and environmental health. Part A. 2009;72:1242–1251. PMID: 2007719
Satratoxin G (SG), a macrocyclic trichothecene produced by Stachybotrys chartarum, induces apoptosis in cultured neuronal cells as well as nasal olfactory sensory neurons (OSN) in the nose and brain of mice exposed intranasally to this toxin. The purposes of this study were to (1) develop a facile method for production and purification of both SG and its putative biosynthetic precursor, roridin L2 (RL2), from S. chartarum cultures and (2) compare their relative neurotoxicity in vitro and in vivo.
Islam Z, Hegg CC, Bae HKK, Pestka JJ. Satratoxin G induced apoptosis in PC-12 neuronal cells is mediated by PKR and caspase independent. Toxicological sciences : an official journal of the Society of Toxicology. 2008;105:142–152. PMID: 18535002
Acute intranasal exposure of mice to Satratoxin G (SG) specifically induces apoptosis in olfactory sensory neurons of the nose. The PC-12 rat pheochromocytoma cell model was used to elucidate potential mechanisms of SG-induced neuronal cell death.
Islam Zahidul, Harkema Jack R., Pestka James J.. Satratoxin G from the black mold Stachybotrys chartarum evokes olfactory sensory neuron loss and inflammation in the murine nose and brain. Environmental health perspectives. 2006;114:1099–1107. PMID: 16835065
Using an intranasal instillation model in mice, we found that acute Satratoxin G exposure specifically induced apoptosis of olfactory sensory neurons (OSNs) in the olfactory epithelium. These findings suggest that neurotoxicity and inflammation within the nose and brain are potential adverse health effects of exposure to satratoxins and Stachybotrys in the indoor air of water-damaged buildings.
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