1. Escitalopram moderately outperforms citalopram towards anti-neuroinflammation and neuroprotection in 6-hydroxydopamine-induced mouse model of Parkinson's disease.
- Author
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Ovlyakulov B, Hu BL, Kan HY, Guo Q, Li XF, Fan HH, Wu HM, Wang JY, Zhang X, and Zhu JH
- Subjects
- Animals, Male, Mice, Neuroinflammatory Diseases drug therapy, Neuroinflammatory Diseases immunology, Mice, Inbred C57BL, Cytokines metabolism, Parkinson Disease drug therapy, Humans, Behavior, Animal drug effects, Dopaminergic Neurons drug effects, Dopaminergic Neurons pathology, Anti-Inflammatory Agents therapeutic use, Anti-Inflammatory Agents pharmacology, Parkinsonian Disorders drug therapy, Parkinsonian Disorders chemically induced, Citalopram pharmacology, Citalopram therapeutic use, Oxidopamine, Neuroprotective Agents therapeutic use, Neuroprotective Agents pharmacology, Disease Models, Animal, Escitalopram therapeutic use, Escitalopram pharmacology
- Abstract
Citalopram and escitalopram are structurally close-related antidepressants and both forms are widely used in the world. We aimed to comparatively evaluate the anti-neuroinflammatory and neuroprotective effects of escitalopram and citalopram in Parkinson's disease (PD) mouse model. Mice were randomly divided into six groups and received 6-hydroxydopamine (6-OHDA) or vehicle administration. The mice were then treated with escitalopram, citalopram or saline for consecutive 7 days. Behaviors, neuroinflammation, neurotransmitters, and neurotoxicity were assessed. Results showed that citalopram but not escitalopram worsened body weight loss and increased freezing time in the PD mice. Both drugs had no impact on the anxiety-like behaviors but ameliorated the depressive-like behaviors as in elevated plus maze and sucrose splash tests. Escitalopram but not citalopram ameliorated motor discoordination in the PD mice as in rotarod test. In accordance, escitalopram but not citalopram attenuated the 6-OHDA-induced nigrostriatal dopaminergic loss. Further mechanistic investigations showed that both drugs mitigated activations of microglia and astrocytes and/or levels of pro-inflammatory cytokines in the PD mice, but escitalopram showed appreciably better effects in the substantia nigra. Neurotransmitter examination in the prefrontal cortex suggested that the two drugs had comparable effects on the disturbed neurotransmitters in the PD mice, but citalopram was prone to disrupt certain normal homeostasis. In conclusion, escitalopram is moderately superior than citalopram to suppress neuroinflammation and to protect against dopaminergic neuronal death and motor discoordination in the 6-OHDA-induced PD mice. Our findings imply that escitalopram shall be prescribed with priority over citalopram to treat PD patients with depression as escitalopram may meanwhile provide greater additional benefits to the patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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