title: Glucose-dependent insulinotropic polypeptide is expressed in adult hippocampus and induces progenitor cell proliferation.
abstract: 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.
authors.affiliation: The Arvid Carlsson Institute for Neuroscience at the Institute of Clinical Neuroscience, Göteborg University, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden. jenny.nyberg@neuro.gu.se
authors.forename: Jenny
authors.initials: J
authors.lastname: Nyberg
authors.forename: Michelle F
authors.initials: MF
authors.lastname: Anderson
authors.forename: Björn
authors.initials: B
authors.lastname: Meister
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Alborn
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Ström
authors.forename: Anke
authors.initials: A
authors.lastname: Brederlau
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Illerskog
authors.forename: Ola
authors.initials: O
authors.lastname: Nilsson
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kieffer
authors.forename: Max Albert
authors.initials: MA
authors.lastname: Hietala
authors.forename: Anne
authors.initials: A
authors.lastname: Ricksten
authors.forename: Peter S
authors.initials: PS
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D020869:Gene Expression Profiling; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D011964:Receptors, Gastrointestinal Hormone / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*
chemical_list: D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor
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