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The Journal of Neuroscience, February 16, 2005, 25(7):1816-1825; doi:10.1523/JNEUROSCI.4920-04.2005

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Cellular/Molecular
Glucose-Dependent Insulinotropic Polypeptide Is Expressed in Adult Hippocampus and Induces Progenitor Cell Proliferation

Jenny Nyberg,¹ Michelle F. Anderson,¹ Björn Meister,⁴ Ann-Marie Alborn,¹ Anna-Karin Ström,¹ Anke Brederlau,⁵ Ann-Christin Illerskog,² Ola Nilsson,² Timothy J. Kieffer,⁶ Max Albert Hietala,¹ Anne Ricksten,³ and Peter S. Eriksson¹

¹The Arvid Carlsson Institute for Neuroscience at the Institute of Clinical Neuroscience and Departments of ²Pathology and ³Clinical Chemistry and Transfusion Medicine, Göteborg University, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden, ⁴Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden, ⁵Institute of Anatomy and Cell Biology, Göteborg University, 405 30 Göteborg, Sweden, and ⁶Departments of Physiology and Surgery, Laboratory of Molecular and Cellular Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada

The hippocampal dentate gyrus (DG) is an area of active proliferation and neurogenesis within the adult brain. The molecular events controlling adult cell genesis in the hippocampus essentially remain unknown. It has been reported previously that adult male and female rats from the strains Sprague Dawley (SD) and spontaneously hypertensive (SHR) have a marked difference in proliferation rates of cells in the hippocampal DG. To exploit this natural variability and identify potential regulators of cell genesis in the hippocampus, hippocampal gene expression from male SHR as well as male and female SD rats was analyzed using a cDNA array strategy. Hippocampal expression of the gene-encoding glucose-dependent insulinotropic polypeptide (GIP) varied strongly in parallel with cell-proliferation rates in the adult rat DG. Moreover, robust GIP immunoreactivity could be detected in the DG. The GIP receptor is expressed by cultured adult hippocampal progenitors and throughout the granule cell layer of the DG, including progenitor cells. Thus, these cells have the ability to respond to GIP. Indeed, exogenously delivered GIP induced proliferation of adult-derived hippocampal progenitors in vivo as well as in vitro, and adult GIP receptor knock-out mice exhibit a significantly lower number of newborn cells in the hippocampal DG compared with wild-type mice. This investigation demonstrates the presence of GIP in the brain for the first time and provides evidence for a regulatory function for GIP in progenitor cell proliferation.

Key words: GIP; hippocampus; proliferation; progenitor cell; dentate gyrus; peptide

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Received Sep 21, 2004; revised December 21, 2004; accepted December 23, 2004.

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