BASAL GANGLIA NEUROTOXINS

Exposure to carbon disulfide (CS₂) has been associated with an increased incidence of parkinsonism in workers, but the mechanism underlying this association remains unclear. Using a rat model, we investigated the effects of chronic CS₂ exposure on parkinsonian pathology. Our results showed that CS₂ exposure leads to significant motor impairment and neuronal damage, including loss of dopaminergic neurons and degeneration of the substantia nigra pars compacta (SNpc). The immunoassays revealed that exposure to CS₂ induces aggregation of α-synuclein and phosphorylated α-synuclein, as well as activation of necroptosis in the SNpc. Furthermore, in vitro and in vivo experiments demonstrated that the interaction between α-synuclein and the necrosome complex (RIP1, RIP3, and MLKL) is responsible for the loss of neuronal cells after CS₂ exposure. Taken together, our results demonstrate that CS₂-mediated α-synuclein aggregation can induce dopaminergic neuron damage and parkinsonian behavior through interaction with the necrosome complex.

Although much of the toxicology of gases (matter consisting of particles that has neither a defined volume nor a defined shape at standard temperatures and pressures) is applicable to the toxicology of vapors, this chapter focuses on substances that meet the criteria for classical gases. The chapter is divided into two overarching sections: general principles and specific toxic gases. Issues pertaining to toxicokinetics and basic dosimetric adjustments for human risk assessment are covered in the general principles section. The section on specific toxic gases covers gases that are of veterinary significance as well as the toxic gases that humans (including veterinarians) are likely to be exposed to in clinical and agricultural settings, such as carbon monoxide, hydrogen sulfide, oxides of nitrogen (silo filler’s disease), gaseous ammonia (including anhydrous ammonia), and smoke inhalation.

Microglia play critical roles in tissue homeostasis and can also modulate neuronal function and synaptic connectivity. In contrast to astrocytes and oligodendrocytes, which arise from multiple progenitor pools, microglia arise from yolk sac progenitors and are widely considered to be equivalent throughout the CNS. However, little is known about basic properties of deep brain microglia, such as those within the basal ganglia (BG). Here, we show that microglial anatomical features, lysosome content, membrane properties, and transcriptomes differ significantly across BG nuclei. Region-specific phenotypes of BG microglia emerged during the second postnatal week and were re-established following genetic or pharmacological microglial ablation and repopulation in the adult, indicating that local cues play an ongoing role in shaping microglial diversity. These findings demonstrate that microglia in the healthy brain exhibit a spectrum of distinct functional states and provide a critical foundation for defining microglial contributions to BG circuit function.

Volatile organic compounds are multifaceted mixtures of low-molecular weight compounds derived from diverse biosynthetic pathways. Fungi are able to produce carbon-based compounds from various mixtures of gas phase. Aspergillus species are excellent producers of a large number of diverse secondary metabolites including aflatoxins, naptho-γ-pyrones, ochratoxins, cyclopiazonic acid, fumonisins, patulin, gliotoxin, kojic acid, malformins, emodin, bicoumarins and csypyrone B1 and DHBA, nitropropionic acid, aflatrem, ophiobolins, etc, and many of these compounds exhibit interesting biological properties. In this chapter collects the most biologically important toxic metabolites of a variety of Aspergillus species are discussed. Aspergillus secondary metabolites have potential biotechnological applications with greater market value beyond those in human health, medicine, industrial production, food, or agricultural industries.