Impact of 5-Lipoxygenase Deficiency on Dopamine-Mediated Behavioral Responses.

Autor: Issy AC; Department of Basic and Oral Biology, Ribeirão Preto School of Dentistry, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil., Pedrazzi JF; Department of Neuroscience and Behavior Sciences, Medical School of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil., Nascimento GC; Department of Basic and Oral Biology, Ribeirão Preto School of Dentistry, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil., Faccioli LH; Department of Clinical Analyses, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Del Bel E; Department of Basic and Oral Biology, Ribeirão Preto School of Dentistry, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil. eadelbel@usp.br.
Jazyk: angličtina
Zdroj: Neurotoxicity research [Neurotox Res] 2024 Oct 04; Vol. 42 (5), pp. 42. Date of Electronic Publication: 2024 Oct 04.
DOI: 10.1007/s12640-024-00720-4
Abstrakt: The 5-lipoxygenase/leukotriene system has been implicated in both physiological and pathological states within the central nervous system. Understanding how this system interacts with the dopaminergic system could provide valuable insights into dopamine-related pathologies. This study focused on examining both motor and non-motor dopamine-related responses in 5-lipoxygenase/leukotriene-deficient mice. We used pharmacological agents such as amphetamine, apomorphine, and reserpine to challenge the dopaminergic system, evaluating their effects on prepulse inhibition reaction (PPI), general motor activity, and oral involuntary movements. Additionally, we analyzed striatal glial marker expression (GFAP and Iba-1) in reserpine-treated mice. The 5-lipoxygenase/leukotriene-deficient mice exhibited increased spontaneous locomotor activity, including both horizontal and vertical exploration, along with stereotyped behavior compared to wild-type mice. This hyperactivity was reduced by acute apomorphine treatment. Although basal PPI responses were unchanged, 5-lipoxygenase/leukotriene-deficient mice displayed a significant reduction in susceptibility to amphetamine-induced PPI disruption. Conversely, these mice were more vulnerable to reserpine-induced involuntary movements. There were no significant differences in the basal expression of striatal GFAP and Iba-1 positive cells between 5-lipoxygenase/leukotriene-deficient and wild-type mice. However, reserpine treatment significantly increased GFAP immunoreactivity in wild-type mice, an effect not observed in 5-lipoxygenase-deficient mice. Additionally, the percentage of activated microglia was significantly higher in reserpine-treated wild-type mice, an effect absents in 5-lipoxygenase/leukotriene-deficient mice. Our findings suggest that 5-lipoxygenase/leukotriene deficiency leads to a distinctive dopaminergic phenotype, indicating that leukotrienes may influence the modulation of dopamine-mediated responses.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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