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

Abstract

The effect of N-methyl-D-aspartate (NMDA) and 2-(aminomethyl)phenylacetic acid/kainate (AMPA/kainate) glutamate receptors on dentate cell proliferation and hippocampal synapsin-I induction was examined after global ischemia. Cell proliferation was assessed using BrdU labeling, and synaptic responses were assessed using synapsin-I expression. Systemic glutamate receptor antagonists (MK-801 and NBQX) increased BrdU-labeled cells in the dentate subgranular zone (SGZ) of control adult gerbils (30% to 90%, P < 0.05). After global ischemia (at 15 days after 10 minutes of ischemia), most CA1 pyramidal neurons died, whereas the numbers of BrdU-labeled cells in the SGZ increased dramatically (>1000%, P < 0.0001). Systemic injections of MK801 or NBQX, as well as intrahippocampal injections of either drug, when given at the time of ischemia completely blocked the birth of cells in the SGZ and the death of CA1 pyramidal neurons at 15 days after ischemia. Glutamate receptor antagonists had little effect on cell birth and death when administered 7 days after ischemia. The induction of synapsin-I protein in stratum moleculare of CA3 at 7 and 15 days after global ischemia was blocked by pretreatment with systemic or intrahippocampal MK-801 or NBQX. It is proposed that decreased dentate glutamate receptor activation--produced by glutamate receptor antagonists in normal animals and by chronic ischemic hippocampal injury--may trigger dentate neurogenesis and synaptogenesis. The synapsin-I induction in mossy fiber terminals most likely represents re-modeling of dentate granule cell neuron presynaptic elements in CA3 in response to the ischemia. The dentate neurogenesis and synaptogenesis that occur after ischemia may contribute to memory recovery after hippocampal injury caused by global ischemia.

• Authors: R Bernabeu, F R Sharp
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 20 Issue 12 Pg. 1669-80 (Dec 2000) ISSN: 0271-678X [Print] United States
• PMID: 11129783 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Excitatory Amino Acid Antagonists
• Neuroprotective Agents
• Quinoxalines
• Receptors, AMPA
• Receptors, Glutamate
• Receptors, Kainic Acid
• Receptors, N-Methyl-D-Aspartate
• Synapsins
• 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
• Glutamic Acid
• Dizocilpine Maleate

Topics

• Animals
• Brain Ischemia (metabolism)
• Cell Division (drug effects, physiology)
• Dentate Gyrus (blood supply, cytology, metabolism)
• Dizocilpine Maleate (pharmacology)
• Down-Regulation (physiology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Gerbillinae
• Glutamic Acid (metabolism)
• Male
• Memory (physiology)
• Microinjections
• Neurons (chemistry, cytology, metabolism)
• Neuroprotective Agents (pharmacology)
• Quinoxalines (pharmacology)
• Receptors, AMPA (metabolism)
• Receptors, Glutamate (metabolism)
• Receptors, Kainic Acid (metabolism)
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Synapsins (analysis, metabolism)