Mold inhalation causes innate immune activation, neural, cognitive and emotional dysfunction.

Individuals living or working in moldy buildings complain of a variety of health problems including pain, fatigue, increased anxiety, depression, and cognitive deficits. The ability of mold to cause such symptoms is controversial since no published research has examined the effects of controlled mold exposure on brain function or proposed a plausible mechanism of action. Patient symptoms following mold exposure are indistinguishable from those caused by innate immune activation following bacterial or viral exposure. We tested the hypothesis that repeated, quantified doses of both toxic and nontoxic mold stimuli would cause innate immune activation with concomitant neural effects and cognitive, emotional, and behavioral symptoms. We intranasally administered either 1) intact, toxic Stachybotrys spores; 2) extracted, nontoxic Stachybotrys spores; or 3) saline vehicle to mice. As predicted, intact spores increased interleukin-1ß immunoreactivity in the hippocampus. Both spore types decreased neurogenesis and caused striking contextual memory deficits in young mice, while decreasing pain thresholds and enhancing auditory-cued memory in older mice. Nontoxic spores also increased anxiety-like behavior. Levels of hippocampal immune activation correlated with decreased neurogenesis, contextual memory deficits, and/or enhanced auditory-cued fear memory. Innate-immune activation may explain how both toxic mold and nontoxic mold skeletal elements caused cognitive and emotional dysfunction.

Differential effects of exposure to toxic or nontoxic mold spores on brain inflammation and Morris water maze performance.

People who live or work in moldy buildings often complain of "brain fog" that interferes with cognitive performance. Until recently, there was no published research on the effects of controlled exposure to mold stimuli on cognitive function or an obvious mechanism of action, fueling controversy over these claims. The constellation of health problems reported by mold-exposed individuals (respiratory issues, fatigue, pain, anxiety, depression, and cognitive deficits) correspond to those caused by innate immune activation following exposure to bacterial or viral stimuli. To determine if mold-induced innate immune activation might cause cognitive issues, we quantified the effects of both toxic and nontoxic mold on brain immune activation and spatial memory in the Morris water maze. We intranasally administered either 1) intact, toxic Stachybotrys chartarum spores; 2) ethanol-extracted, nontoxic Stachybotrys chartarum spores; or 3) control saline vehicle to mice. Inhalation of nontoxic spores caused significant deficits in the test of long-term memory of platform location, while not affecting short-term memory. Inhalation of toxic spores increased motivation to reach the platform. Interestingly, in both groups of mold-exposed males, numbers of interleukin-1ß-immunoreactive cells in many areas of the hippocampus significantly correlated with latency to find the platform, path length, and swimming speed during training, but not during testing for long-term memory. These data add to our prior evidence that mold inhalation can interfere with cognitive processing in different ways depending on the task, and that brain inflammation is significantly correlated with changes in behavior.