Melatonin Rescues the Dendrite Collapse Induced by the Pro-Oxidant Toxin Okadaic Acid in Organotypic Cultures of Rat Hilar Hippocampus

Autor: Héctor Solís-Chagoyán, Aline Domínguez-Alonso, Marcela Valdés-Tovar, Jesús Argueta, Zuly A. Sánchez-Florentino, Eduardo Calixto, Gloria Benítez-King
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Molecules, Vol 25, Iss 23, p 5508 (2020)
Druh dokumentu: article
ISSN: 25235508
1420-3049
57034982
DOI: 10.3390/molecules25235508
Popis: The pro-oxidant compound okadaic acid (OKA) mimics alterations found in Alzheimer’s disease (AD) as oxidative stress and tau hyperphosphorylation, leading to neurodegeneration and cognitive decline. Although loss of dendrite complexity occurs in AD, the study of this post-synaptic domain in chemical-induced models remains unexplored. Moreover, there is a growing expectation for therapeutic adjuvants to counteract these brain dysfunctions. Melatonin, a free-radical scavenger, inhibits tau hyperphosphorylation, modulates phosphatases, and strengthens dendritic arbors. Thus, we determined if OKA alters the dendritic arbors of hilar hippocampal neurons and whether melatonin prevents, counteracts, or reverses these damages. Rat organotypic cultures were incubated with vehicle, OKA, melatonin, and combined treatments with melatonin either before, simultaneously, or after OKA. DNA breaks were assessed by TUNEL assay and nuclei were counterstained with DAPI. Additionally, MAP2 was immunostained to assess the dendritic arbor properties by the Sholl method. In hippocampal hilus, OKA increased DNA fragmentation and reduced the number of MAP2(+) cells, whereas melatonin protected against oxidation and apoptosis. Additionally, OKA decreased the dendritic arbor complexity and melatonin not only counteracted, but also prevented and reversed the dendritic arbor retraction, highlighting its role in post-synaptic domain integrity preservation against neurodegenerative events in hippocampal neurons.
Databáze: Directory of Open Access Journals
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