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Peptide hormone exendin‐4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of parkinson's disease
Author(s) -
Bertilsson Göran,
Patrone Cesare,
Zachrisson Olof,
Andersson Annica,
Dannaeus Karin,
Heidrich Jessica,
Kortesmaa Jarkko,
Mercer Alex,
Nielsen Elisabet,
Rönnholm Harriet,
Wikström Lilian
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21483
Subject(s) - subventricular zone , neurogenesis , doublecortin , neural stem cell , biology , substantia nigra , tyrosine hydroxylase , neuroblast , bromodeoxyuridine , progenitor cell , rostral migratory stream , dopamine , dopaminergic , endocrinology , medicine , stem cell , microbiology and biotechnology , hippocampal formation , immunology , immunohistochemistry , dentate gyrus
We investigated the effects of exendin‐4 on neural stem/progenitor cells in the subventricular zone of the adult rodent brain and its functional effects in an animal model of Parkinson's disease. Our results showed expression of GLP‐1 receptor mRNA or protein in the subventricular zone and cultured neural stem/progenitor cells isolated from this region. In vitro, exendin‐4 increased the number of neural stem/progenitor cells, and the number of cells expressing the neuronal markers microtubule‐associated protein 2, β‐III‐tubulin, and neuron‐specific enolase. When exendin‐4 was given intraperitoneally to naïve rodents together with bromodeoxyuridine, a marker for DNA synthesis, both the number of bromodeoxyuridine‐positive cells and the number of neuronal precursor cells expressing doublecortin were increased. Exendin‐4 was tested in the 6‐hydroxydopamine model of Parkinson's disease to investigate its possible functional effects in an animal model with neuronal loss. After unilateral lesion and a 5‐week stabilization period, the rats were treated for 3 weeks with exendin‐4. We found a reduction of amphetamine‐induced rotations in animals receiving exendin‐4 that persisted for several weeks after drug administration had been terminated. Histological analysis showed that exendin‐4 significantly increased the number of both tyrosine hydroxylase‐ and vesicular monoamine transporter 2‐positive neurons in the substantia nigra. In conclusion, our results show that exendin‐4 is able to promote adult neurogenesis in vitro and in vivo, normalize dopamine imbalance, and increase the number of cells positive for markers of dopaminergic neurons in the substantia nigra in a model of Parkinson's disease. © 2007 Wiley‐Liss, Inc.