Melatonin Rescues the Dendrite Collapse Induced by the Pro-Oxidant Toxin Okadaic Acid in Organotypic Cultures of Rat Hilar Hippocampus
| Autor: | Aline Domínguez-Alonso, Eduardo Calixto, Jesús Argueta, Marcela Valdés-Tovar, Héctor Solís-Chagoyán, Gloria Benítez-King, Zuly A Sánchez-Florentino |
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| Rok vydání: | 2020 |
| Předmět: |
hippocampus
education Pharmaceutical Science melatonin DNA fragmentation Hippocampal formation medicine.disease_cause Article Analytical Chemistry lcsh:QD241-441 Melatonin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine lcsh:Organic chemistry okadaic acid Drug Discovery medicine Animals hilus dendrite complexity DAPI Physical and Theoretical Chemistry Cognitive decline 030304 developmental biology 0303 health sciences TUNEL assay Organic Chemistry Neurodegeneration neurodegeneration Dendrites Okadaic acid Oxidants medicine.disease Immunohistochemistry humanities Rats Cell biology Organoids Oxidative Stress Neuroprotective Agents chemistry Chemistry (miscellaneous) Molecular Medicine Reactive Oxygen Species Oxidation-Reduction 030217 neurology & neurosurgery Oxidative stress medicine.drug |
| Zdroj: | Molecules, Vol 25, Iss 5508, p 5508 (2020) Molecules Volume 25 Issue 23 |
| ISSN: | 1420-3049 |
| Popis: | The pro-oxidant compound okadaic acid (OKA) mimics alterations found in Alzheimer&rsquo 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: | OpenAIRE |
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