NeuralCipher Research overview
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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.
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