Inflammatory reaction regulated by microglia plays a role in atrazine-induced dopaminergic neuron degeneration in the substantia nigra

Abstract

-Atrazine (ATR) is a widely used herbicide, although it is potentially ecotoxic. Increasing evidence indicates that ATR plays a critical role in inducing physiological changes to the endocrine and reproductive systems, and further may affect the nigrostriatal dopaminergic system in the diencephalon, resulting in altered dopamine (DA) levels in the striatum, transport and storage-related protein abnormalities in the synaptic terminals, motor function deficits, and degeneration of DA neurons in the substantia nigra (SN). As the primary immunocytes in the central nervous system (CNS), microglial function to maintain the CNS microenvironment by preventing damage to healthy cells as well by regulating inflammatory responses. Several studies have demonstrated that microglial activation exerted an important effect on neuronal degeneration. In order to investigate dynamic changes of the microglial phenotype in the SN, rats received consecutive intraperitoneal injections of a vehicle or ATR at 25, 50, or 100 mg/kg body weight for a 14-day period and were then sacrificed at 1, 4, 7, or 14 days post-treatment, respectively. Here, we found that microglial activation by changes to phenotype emerged later in the low ATR exposure group than in the medium and high ATR exposure groups, and proliferating microglia were observed as well. Moreover, as two major inflammatory cytokines, expression of tumor necrosis factor α and interleukin-1β, emerged earlier post-ATR exposure, and a significant upregulation was observed in the medium and high ATR exposure groups. These results suggested that inflammatory reactions regulated by microglia occurred in a dose-and time-dependent manner, which may explain the severe DA neuron degeneration with the phagocytic phenotype of microglia in the SN that emerged earlier in the medium and high ATR exposure groups than in the low ATR exposure group. Taken together, our findings suggest that microglial activation might be involved in the dose-and time-dependent ATR-induced DA neuron degeneration in the SN.

Lycopene ameliorates atrazine-induced pyroptosis in spleen by suppressing the Ox-mtDNA/Nlrp3 inflammasome pathway

“…See DOI: 10.1039/d1fo02857j Some studies have found that ATZ could induce inflammation in some tissues. [22][23][24] In addition, ATZ exposure can result in ROS generation and accumulation in its target organs. Thus, it could be hypothesized that ATZ induced the activation of Nlrp3, which could trigger autoinflammatory and metabolic disorders in human.…”

Endocrine disruptors also function as nervous disruptors and can be renamed endocrine and nervous disruptors (ENDs)

“… 5 Aroclor 1254 PCB mixture Mucio-Ramírez et al [ 41 ]: decrease somatodendritic vasopressin release Wei et al [ 42 ]: oxidative stress in the brain Coburn et al [ 43 ]: Inhibition of vasopressin release from magnocellular neuroendocrine cells Majumdar et al [ 44 ]: induces oxidative stress in the brain Tilson et al [ 45 ]: increases translocation of protein kinase C and decreases Ca2+-buffering in the brain 6 Arsenic (As) Heavy metal, pesticide Liu et al [ 46 ]: cognitive impairment Webb et al [ 47 ]: chronic neurological disease Preciados et al [ 48 ]: influence nuclear respiratory factor 1 by genomic and epigenomic networks, this contributes in the development of complex chronic human brain disorders Karri et al [ 49 ]: pro-oxidant elements dominate antioxidants factors and leads to cognitive dysfunction Tyler at al. [ 50 ]: alters epigenetics and hippocampal function, glutamatergic, cholinergic and monoaminergic signaling; altered adult neurogenesis; and increases Alzheimer's-associated pathologies 7 Atrazine Herbicide Ma et al [ 51 ]: reduces dopamine levels in the substantia nigra and corpus striatum in the midbrain Zhang et al [ 52 ]: severe dopamine neuron degeneration Lin et al [ 53 ]: increases in striatal dopamine; decreases in perirhinal cortex serotonin Ottinger et al [ 54 ]: impact on arginine vasotocin, catecholamines and gonadotropin releasing hormone. 8 Benzo(a)anthracene …”

Inhibition of the hepatic Nlrp3 protects dopaminergic neurons via attenuating systemic inflammation in a MPTP/p mouse model of Parkinson’s disease

“…5 c). The change of brain microenvironment and microglia activation induced dopaminergic neuronal injury [ 21 , 27 ]. We used TH antibody-labeled DA neurons via immunohistochemistry, where the siRNA injected via tail vein had no effects on DA neurons at the basal line.…”