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Verapamil prevents, in a dose-dependent way, the loss of ChAT-immunoreactive neurons in the cerebral cortex following lesions of the rat nucleus basalis magnocellularis

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Abstract

In the present study we analysed the neuroprotective effect of the L-type voltage-dependent calcium channel antagonist verapamil on cholineacetyltransferase (ChAT)-immunoreactive neurons in the cerebral cortex of rats with bilateral electrolytic lesions of the nucleus basalis magnocellularis (NBM). Treatment with verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg/12 h i.p.) started 24 h after NBM lesions and lasted 8 days. Animals were sacrificed on day 21 after NBM-lesions. The bilateral NBM-lesions produced significant loss of ChAT-immunoreactive neurons in frontal, parietal and temporal cortex. Although the number of ChAT-positive neurons was significantly higher in NBM-lesioned animals treated with verapamil at a dose of 2.5, 5.0 and 10.0 mg/kg than in saline treated ones, the most significant effect was obtained at a dose of 5 mg/kg. This is, to our knowledge, the first report showing an inverted U-shape mode of neuroprotective action of the calcium antagonist verapamil, at morphological level in this particular model of brain damage. The demonstrated beneficial effect of verapamil treatment suggests that the regulation of calcium homeostasis during the early period after NBM lesions might be a possible treatment to prevent neurodegenerative processes in the rat cerebral cortex.

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Acknowledgements

This study was supported by grants from Fundación Séneca, Centro de Coordinación de la Investigación, Murcia, Spain (PB/4/FS/97) (M.C.B.), Red CIEN-Nodo Facultad de Medicina de Murcia, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Spain and DGI2001 (L.P.).

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Authors and Affiliations

  1. Departamento de Anatomía Humana y Psicobiología, Facultad de Medicina, Campus Universitario de Espinardo, Universidad de Murcia, 30100, Murcia, Spain

    Miroljub Popović, Maria Caballero-Bleda & Luis Puelles

  2. Instituto del Envejecimiento, Universidad de Murcia, 30100, Murcia, Spain

    Miroljub Popović, Maria Caballero-Bleda & Luis Puelles

  3. Neuronal Survival Unit, Division of Neuroscience, Department of Experimental Medical Science, Wallenberg Neuroscience Center, BMC A10, Lund University, 22184, Lund, Sweden

    Natalija Popović

  4. Department of Neuroscience and Neurology, University of Kuopio, P.O. Box 1627, 70211, Kuopio, Finland

    Thomas van Groen

  5. Department of Anatomy, Research Institute Neurosciences, Vrije Universiteit Medical Center, Graduate School Neurosciences Amsterdam, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands

    Menno P. Witter

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  1. Miroljub Popović
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  2. Maria Caballero-Bleda
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Correspondence to Miroljub Popović.

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Popović, M., Caballero-Bleda, M., Popović, N. et al. Verapamil prevents, in a dose-dependent way, the loss of ChAT-immunoreactive neurons in the cerebral cortex following lesions of the rat nucleus basalis magnocellularis. Exp Brain Res 170, 368–375 (2006). https://doi.org/10.1007/s00221-005-0219-3

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