Rotenone Induces Morphological Damage and Reduction in Catecholamine Levels in the Central Nervous System of the Ascidian <i>Styela plicata</i>

Ascidians are invertebrates that occupy a key phylogenetic position as a sister group of the vertebrates. The organization of their central nervous system (CNS), with cortex and medulla, indicates a plesiomorphic character of the gray and white matter of vertebrates, making this group of animals useful for studies of neurodegenerative events. Rotenone, a natural pesticide extracted from the roots of specific plants, can be used as a neurotoxin to promote parkinsonism in various organism models, leading to degeneration of the dopaminergic neurons, mitochondrial dysfunction, and locomotor deficit. Due to the increased use of invertebrates in neurodegenerative studies, we investigated the effect of systemic injections of rotenone on the ascidian Styela plicata CNS, focusing on histological, cellular, and physiological effects on the catecholaminergic pathway. An immunohistochemical analysis revealed the presence of the enzyme tyrosine hydroxylase (TH) in the cerebral ganglion and that dopaminergic neurons were affected by rotenone, in the doses used, as confirmed by the increase in labeling of cleaved caspase-3. Ultrastructural analyses showed that rotenone promoted alterations in the nuclear and mitochondrial organization, consistent with apoptosis, and biochemical analyses revealed reduced catecholamines and TH levels. Our results indicated that ascidians may serve as useful, simple, and ethically favorable animals to study neurodegenerative conditions, including Parkinson's disease. Additionally, they are found in abundance in the oceans and are easy to obtain and maintain in aquaria at low cost, which facilitates their use as models.