Nifedipine and nimodipine protect dopaminergic substantia nigra neurons against axotomy-induced cell death in rat vibrosections via modulating inflammatory responses.
Brain Res
; 1581: 1-11, 2014 Sep 18.
Article
en En
| MEDLINE
| ID: mdl-25038562
ABSTRACT
Neurodegeneration of cholinergic and dopaminergic neurons is a major hallmark in Alzheimer's or Parkinson's disease, respectively. A dysregulation in calcium homeostasis may be part of this process and counteracting calcium influx may have neuroprotective properties in both diseases. Therefore, we investigated the putative neuroprotective or neurotoxic activity of L-type calcium channel (LTCC) inhibitors on cholinergic and dopaminergic neurons in a rat organotypic vibrosection model. Sagittal or coronal vibrosections (200 µm thick) of postnatal day 10 rats were cultured on 0.4 µm semipermeable membranes for 2 weeks with 10 ng/ml nerve growth factor (NGF) and/or glial-cell line derived neurotrophic factor (GDNF) to maintain survival of cholinergic or dopaminergic neurons, respectively. Thereafter, sections were incubated with 0.1, 1 or 10 µM isradipine, nicardipine or verapamil for 2 weeks to explore cytotoxicity. Alternatively, in order to explore neuroprotective activity, vibrosections were incubated without growth factors but with isradipine or verapamil or with nicardipine, nimodipine or nifedipine from the beginning for 4 weeks. Our data show that all LTCC inhibitors exhibited no neurotoxic effect on cholinergic and dopaminergic neurons. Further, LTCC inhibitors did not have any neuroprotective activity on cholinergic neurons. However, nimodipine and nifedipine significantly enhanced the survival of dopaminergic substantia nigra (SN) but not ventral tegmental area (VTA) neurons, while nicardipine, isradipine and verapamil had no effect. Nifedipine (and more potently GDNF) reduced inflammatory cytokines (macrophage inflammatory protein-2, tumor necrosis factor-α), but did not influence oxidative stress or caspase-3 activity and did not interfere with iron-mediated overload. Our data show that nifedipine and nimodipine are very potent to enhance the survival of axotomized SN neurons, possibly influencing inflammatory processes.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Sustancia Negra
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Nifedipino
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Nimodipina
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Muerte Celular
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Fármacos Neuroprotectores
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Neuronas Dopaminérgicas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2014
Tipo del documento:
Article