Glucose-dependent insulinotropic polypeptide is expressed in adult hippocampus and induces progenitor cell proliferation.

• 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.

Keyword

Animals

Cell Division

drug effects

Dentate Gyrus

cytology

metabolism

Female

Gastric Inhibitory Polypeptide

biosynthesis

genetics

pharmacology

physiology

Gene Expression Profiling

Hypertension

genetics

metabolism

Male

Mice

Mice

Inbred C57BL

Mice

Knockout

Neurons

cytology

drug effects

Oligonucleotide Array Sequence Analysis

Rats

Rats

Inbred SHR

Rats

Sprague-Dawley

Receptors

Gastrointestinal Hormone

deficiency

genetics

physiology

Stem Cells

cytology

Publication and Content Type

ref (subject category)

art (subject category)