The Protective Effect of Lithium Against Rotenone may be Evolutionarily Conserved: Evidence from Eisenia fetida, a Primitive Animal with a Ganglionic Brain

Chronic exposure to stress is a non-adaptive situation that is associated with mitochondrial dysfunction and the accumulation of reactive oxygen species (ROS), especially superoxide anion (SA). This accumulation of ROS produces damage-associated molecular patterns (DAMPs), which activate chronic inf...

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Published in:Neurochemical research 2023-12, Vol.48 (12), p.3538-3559
Main Authors: Mastella, Moisés Henrique, Roggia, Isabel, Turra, Bárbara Osmarin, de Afonso Bonotto, Nathália Cardoso, Teixeira, Cibele Ferreira, Pulcinelli, Débora Luisa Filipetto, Meira, Graziela Moro, Azzolin, Verônica Farina, de Morais-Pinto, Luciano, Barbisan, Fernanda, da Cruz, Ivana Beatrice Mânica
Format: Article
Language:English
Subjects:
Acetylcholine receptors (nicotinic)
Anti-inflammatory agents
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Chronic exposure
Damage accumulation
Damage assessment
Damage patterns
Disorders
Eisenia fetida
Evolution
Exposure
Gene expression
Impulsive behavior
Inflammation
Leukocytes (neutrophilic)
Lithium
Lithium carbonate
Mental disorders
Mitochondria
Neurochemistry
Neurology
Neurosciences
Nitric oxide
Oligochaeta
Original Paper
Reactive oxygen species
Rotenone
Scanning electron microscopy
Superoxide anions
Worms
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Summary:Chronic exposure to stress is a non-adaptive situation that is associated with mitochondrial dysfunction and the accumulation of reactive oxygen species (ROS), especially superoxide anion (SA). This accumulation of ROS produces damage-associated molecular patterns (DAMPs), which activate chronic inflammatory states and behavioral changes found in several mood disorders. In a previous study, we observed that an imbalance of SA triggered by rotenone (Ro) exposure caused evolutionarily conserved oxi-inflammatory disturbances and behavioral changes in Eisenia fetida earthworms. These results supported our hypothesis that SA imbalance triggered by Ro exposure could be attenuated by lithium carbonate (LC), which has anti-inflammatory properties. The initial protocol exposed earthworms to Ro (30 nM) and four different LC concentrations. LC at a concentration of 12.85 mg/L decreased SA and nitric oxide (NO) levels and was chosen to perform complementary assays: (1) neuromuscular damage evaluated by optical and scanning electron microscopy (SEM), (2) innate immune inefficiency by analysis of Eisenia spp. extracellular neutrophil traps (eNETs), and (3) behavioral changes. Gene expression was also evaluated involving mitochondrial ( COII, ND1 ), inflammatory ( EaTLR, AMP ), and neuronal transmission ( nAchR α5 ). LC attenuated the high melanized deposits in the circular musculature, fiber disarrangement, destruction of secretory glands, immune inefficiency, and impulsive behavior pattern triggered by Ro exposure. However, the effects of LC and Ro on gene expression were more heterogeneous. In summary, SA imbalance, potentially associated with mitochondrial dysfunction, appears to be an evolutionary component triggering oxidative, inflammatory, and behavioral changes observed in psychiatric disorders that are inhibited by LC exposure.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-023-04001-y