NMDA and AMPA/kainite receptors modulate dentate neurogenesis and CA3 synapsin-I in normal and ischemic hippocampus.

BERNABEU, R AND SHARP, FR

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Nature

Año: 2000 vol. 20 p. 1669 - 1680

0271-678X

Summary: The effect of N-methyl-D-aspartate (NMDA) and2-(aminomethyl)phenylacetic acid/kainate (AMPA/kainate)glutamate receptors on dentate cell proliferation and hippocampalsynapsin-I induction was examined after global ischemia.Cell proliferation was assessed using BrdU labeling, and synapticresponses were assessed using synapsin-I expression. Systemicglutamate receptor antagonists (MK-801 and NBQX) increasedBrdU-labeled cells in the dentate subgranular zone(SGZ) of control adult gerbils (30% to 90%, P < 0.05). Afterglobal ischemia (at 15 days after 10 minutes of ischemia), mostCA1 pyramidal neurons died, whereas the numbers of BrdUlabeledcells in the SGZ increased dramatically (>1000%, P <0.0001). Systemic injections of MK801 or NBQX, as well asintrahippocampal injections of either drug, when given at thetime of ischemia completely blocked the birth of cells in theSGZ and the death of CA1 pyramidal neurons at 15 days afterischemia. Glutamate receptor antagonists had little effect oncell birth and death when administered 7 days after ischemia.The induction of synapsin-I protein in stratum moleculare ofCA3 at 7 and 15 days after global ischemia was blocked bypretreatment with systemic or intrahippocampal MK-801 orNBQX. It is proposed that decreased dentate glutamate receptoractivation—produced by glutamate receptor antagonists in normalanimals and by chronic ischemic hippocampal injury—may trigger dentate neurogenesis and synaptogenesis. The synapsin-I induction in mossy fiber terminals most likely representsre-modeling of dentate granule cell neuron presynapticelements in CA3 in response to the ischemia. The dentateneurogenesis and synaptogenesis that occur after ischemiamay contribute to memory recovery after hippocampal injurycaused by global ischemia.