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Vasoactive Intestinal Peptide (VIP) Treatment of Parkinsonian Rats Increases Thalamic Gamma-Aminobutyric Acid (GABA) Levels and Alters the Release of Nerve Growth Factor (NGF) by Mast Cells

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Abstract

The ventral anterior nucleus of the thalamus (VATh) gathers motor information from the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNpr) of the basal ganglia and projects directly to motor areas of cortex. GPi/SNpr send their tonically active gamma-aminobutyric acid (GABA)ergic outputs to VATh. The abnormal firing patterns of GABAergic neurons in GPi/SNpr lead to motor deficits. In Parkinson’s disease, the spontaneous firing pattern of GPi/SNpr neurons is abnormal due to the degeneration of the nigrostriatal dopaminergic pathway. In a previous study, we found that systemically administered vasoactive intestinal peptide (VIP) was effective at reversing the motor deficits (but not the decline in striatal dopamine levels) in a rat model of Parkinson’s disease (6-hydroxydopamine (6-OHDA) exposure). In addition to the beneficial effects on the motor response, VIP could also attenuate both neuronal cell death and the characteristic loss of the myelin sheath that is associated with 6-OHDA administration into the rat striatum. VIP was thought to preserve neurons by inducing native brain mast cells to adopt a nondegranulating phenotype that had the ability to secrete numerous neuroprotective substances, such as nerve growth factor (NGF) and heparin. In the present study, the effect of systemically administered VIP (25 ng/kg i.p.) was investigated on GABA levels of the VATh, dopamine/3,4-dihydroxyphenylacetic acid (DOPAC) levels in the corpus striatum, and the NGF, rat mast cell protease II (RMCPII), serotonin, and heparin content of brain mast cells in 6-OHDA-lesioned rats. Extracellular concentrations of GABA, dopamine, and DOPAC were measured by microdialysis and high-performance liquid chromatography. NGF, RMCPII, serotonin, and heparin levels were examined by immunohistochemical staining techniques. A total of 48 young adult Sprague–Dawley rats were used in the study, and these were assigned to one of six groups. Unilateral injection of 6-OHDA, 2 µl (6 mg/µl), was made into the right corpus striatum. VIP-treated animals received 25 ng/kg VIP i.p. at 2-day intervals for a period of 15 days. The present results demonstrated that VIP significantly increased the levels of GABA in the VATh that were reduced by 6-OHDA application and increased the number of NGF-immunoreactive mast cells but did not alter dopamine metabolism. Therefore, the protective effect of VIP on motor function is possibly related to the increased levels of GABA in the VATh, and its neuroprotective actions may be mediated by the release of NGF from brain mast cells.

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Abbreviations

VATh:

Ventral anterior nucleus of the thalamus

GPi:

Internal segment of the globus pallidus

GPe:

External segment of the globus pallidus

SNpr:

Substantia nigra pars reticulata

SNpc:

Substantia nigra pars compacta

VIP:

Vasoactive intestinal peptide

NGF:

Nerve growth factor

6-OHDA:

6-Hydroxydopamine

DOPAC:

3,4-Dihydroxyphenylacetic acid

RMCPII:

Rat mast cell protease II

STN:

Subthalamic nucleus

TB:

Toluidine blue

ERK1/2/MAP kinase:

Extracellular signal-regulated kinase/mitogen-activated protein kinase

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Acknowledgments

We would like to thank Dr. Luigi Aloe, Institute of Neurobiology and Molecular Medicine, National Research Council, NGF Section, Via Del Fosso di Fiorano 64, 00143, Rome, Italy, who kindly donated the NGF antibody.

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Authors and Affiliations

  1. Department of Physiology, Medical Faculty, Eskişehir Osmangazi University, 26480, Eskişehir, Turkey

    Orhan Tansel Korkmaz & Neşe Tunçel

  2. Analytical Chemistry Department, Pharmacy Faculty, Anadolu University, 26040, Eskişehir, Turkey

    Muzaffer Tunçel

  3. Department of Chemistry, Art and Science Faculty, Anadolu University, 26040, Eskişehir, Turkey

    Elif Mine Öncü

  4. Histology–Embryology Department, Medical Faculty, Eskişehir Osmangazi University, 26480, Eskişehir, Turkey

    Varol Şahintürk & Mustafa Çelik

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  1. Orhan Tansel Korkmaz
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  2. Neşe Tunçel
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  4. Elif Mine Öncü
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Correspondence to Neşe Tunçel.

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Korkmaz, O.T., Tunçel, N., Tunçel, M. et al. Vasoactive Intestinal Peptide (VIP) Treatment of Parkinsonian Rats Increases Thalamic Gamma-Aminobutyric Acid (GABA) Levels and Alters the Release of Nerve Growth Factor (NGF) by Mast Cells. J Mol Neurosci 41, 278–287 (2010). https://doi.org/10.1007/s12031-009-9307-3

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