Parkinson’s disease (PD), the second most common neurodegenerative disorder, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and non-motor symptoms. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been extensively used in different animal species to develop chemical models of PD. This study aimed to evaluate the effects of acute exposure to MPTP (3 × 150 mg/kg, intraperitoneally) on adult zebrafish by assessing the neurochemical, transcriptional, and motor changes associated with PD pathogenesis. MPTP treatment resulted in a significant decrease in brain catecholamines, including dopamine, norepinephrine, and normetanephrine. Additionally, a trend towards decreased levels of dopamine precursors (tyrosine and L-DOPA) and degradation products (3-MT and DOPAC) was also observed, although these changes were not statistically significant. Gene expression analysis showed the downregulation of dbh, while the expression of other genes involved in catecholamine metabolism (th1, th2, mao, comtb) and transport (slc6a3 and slc18a2) remained unaltered, suggesting a lack of dopaminergic neuron degeneration. Behavioral assessments revealed that MPTP-exposed zebrafish exhibited reduced motor activity, consistent with the observed decrease in dopamine levels. In contrast, the kinematic parameters of sharp turning were unaffected. A significant impairment in the sensorimotor gating of the ASR was detected in the MPTP-treated fish, consistent with psychosis. Despite dopamine depletion and behavioral impairments, the absence of neurodegeneration and some hallmark PD motor symptoms suggests limitations in the validity of this model for fully recapitulating PD pathology. Further studies are needed to refine the use of MPTP in zebrafish PD models.

Gut microbiome dysbiosis is a major off-target effect of many pharmaceuticals, personal care products (PPCP), and plant protection products (PPP). This study aims to characterize these effects for two compounds, glyphosate (a PPP) and triclosan (a PPCP), in Daphnia magna juveniles and to trace the downstream consequences for gut- and brain-associated metabolite levels, reproductive performance, and behavior. Both compounds altered levels of neurotransmitters and related metabolites in both head and gut at the ppb-ppt dose range, promoting anxiogenic behavior and inhibiting reproductive traits in a concentration-related manner. These effects occurred concomitantly with alterations in the gut microbiome, analyzed by 16S rDNA sequencing. Correlation analyses between the observed metabolic, reproductive, and behavioral effects and the changes in the metabolic pathway prediction for the treated gut microbiomes revealed an enrichment in pathways related to the biosynthesis of vitamins, of essential fatty acids, and production of short chain fatty acids, which are known to affect systemic serotonin levels. The results suggest a direct link between gut microbiome dysbiosis and cognitive and reproduction effects in D. magna, with implications for the environmental and human health hazard assessment of these and other substances with broad antimicrobial spectra.

Parkinson's disease (PD), the second most common neurodegenerative disorder, involves the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, resulting in motor and non-motor symptoms. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is widely used to develop chemical models of PD. This study evaluates the effects of acute MPTP exposure (3 x 150 mg/kg bw, intraperitoneally) on adult zebrafish by analyzing neurochemical, transcriptional, motor, and non-motor changes linked to PD. MPTP exposure significantly reduced brain catecholamines, including dopamine, norepinephrine, and normetanephrine, while gene expression analysis revealed no significant changes in the expression of genes related with catecholamine metabolism (th1, th2, mao, comtb, dbh) and transport (slc6a3 and slc18a2), suggesting a lack of dopaminergic neuron degeneration. Behaviorally, MPTP-treated zebrafish exhibited reduced motor activity consistent with lower dopamine levels. The kinematic analysis of the sharp turn showed a tendency to increase the duration of this maneuver, although this effect was not statistically significant. Furthermore, sensorimotor gating of the acoustic startle response (ASR) was significantly impaired, aligning with PD psychosis-like symptoms. Further studies are required to validate and refine the use of MPTP-based PD models in adult zebrafish.

Acrylamide (ACR) is a potent neurotoxicant that disrupts cellular redox homeostasis by depleting reduced glutathione (GSH) and inducing oxidative stress. Despite its well-characterized mechanism, effective treatments for ACR-induced neurotoxicity remain elusive. This study evaluates the therapeutic potential of N-acetylcysteine-amide (AD4), a blood-brain barrier-permeable derivative of N-acetylcysteine, in a novel severe acute ACR neurotoxicity model in adult zebrafish. Intraperitoneal administration of a single high dose of ACR (800 mg/kg) resulted in a 51% reduction in brain GSH levels, which was fully rescued by AD4 treatment. Behavioral analyses revealed that ACR exposure impaired short-term habituation of the acoustic startle response (ASR), a deficit that was mitigated by AD4. Surprisingly, ACR exposure did not alter the neurochemical profile of key neurotransmitters or the expression of genes related to redox homeostasis, synaptic vesicle recycling, regeneration, or myelination. These findings highlight the efficacy of AD4 in counteracting ACR-induced oxidative stress and behavioral deficits, underscoring its potential as a therapeutic agent for ACR neurotoxicity. This study also validates the adult zebrafish as a translational model to investigate neurotoxic mechanisms and evaluate neuroprotective interventions.