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Vasoactive Intestinal Peptide Enhances Striatal Plasticity and Prevents Dopaminergic Cell Loss in Parkinsonian Rats

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Abstract

Destruction of the nigrostriatal dopaminergic pathway by the administration of 6-OHDA generates an animal model of Parkinson's disease. The main characteristic of this progressive neurological disorder is the loss of the dopaminergic neurons located in the substantia nigra pars compacta (SNc). Dopaminergic inputs from the SNc innervate the medium spiny neurons of the striatum and modulate the spontaneous activity of the primary output nuclei of the basal ganglia, globus pallidus interna, and substantia nigra pars reticulata. In our previous studies, we showed that systematically administered vasoactive intestinal peptide (VIP) is effective at reversing motor deficits, decreasing neuronal cell death, and repairing the myelin sheet in parkinsonian rats. In the current study, the effects of VIP on the dendritic morphology of the striatal neurons and the number of dopaminergic neurons in the SNc were examined in 6-OHDA-lesioned rats using Golgi-Cox staining and design-based stereological methods, respectively. Adult Sprague-Dawley rats were separated into sham-operated, bilaterally 6-OHDA lesioned and lesioned + i.p. VIP-injected (25 ng/kg) groups. VIP was first injected 1 h after the intrastriatal 6-OHDA microinjection (every 2 days for 15 days). The 6-OHDA significantly decreased the total number of dopaminergic neurons, branching, and spine density of the medium spiny neurons in the striatum. VIP significantly increased the number of neurons immunostained with tyrosine hydroxylase and the density of spines without altering the branching and the total length of dendrites. In conclusion, VIP might display synaptogenetic activity by enhancing the spine density in the striatum of the parkinsonian rats.

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Authors and Affiliations

  1. Department of Physiology and Neurophysiology, Medical Faculty, Eskişehir Osmangazi University, 26040, Eskisehir, Turkey

    OrhanTansel Korkmaz & Neşe Tunçel

  2. Department of Anatomy, Medical Faculty, Eskişehir Osmangazi University, Eskisehir, Turkey

    Hakan Ay & Emel Ulupınar

  3. Department of Veterans Affairs, VA Boston Healthcare System, 02130, Boston, MA, USA

    OrhanTansel Korkmaz

  4. Department of Neurology, School of Medicine, Boston University, 02118, Boston, MA, USA

    OrhanTansel Korkmaz

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  1. OrhanTansel Korkmaz
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  2. Hakan Ay
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  4. Neşe Tunçel
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Correspondence to Neşe Tunçel.

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Korkmaz, O., Ay, H., Ulupınar, E. et al. Vasoactive Intestinal Peptide Enhances Striatal Plasticity and Prevents Dopaminergic Cell Loss in Parkinsonian Rats. J Mol Neurosci 48, 565–573 (2012). https://doi.org/10.1007/s12031-012-9781-x

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  • DOI: https://doi.org/10.1007/s12031-012-9781-x

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