Uncontrolled Ca2+ flux is thought to orchestrate cell death due to excitatory amino acids. Studies suggest a relationship between calcium-binding proteins (CaBPs) and resistance to excitotoxicity. It is not clear, however, if neurons survive due to an absolute resistance to the excitotoxin. For example, in chick retina, NMDA kills most amacrine and some ganglion cells, whereas other retinal populations are unaffected. The resistance of neurons in the outer layers of retina is due to the absence of NMDA receptors on these cells. Amacrine neurons in retina are ideal to study the relationship between CaBPs and excitotoxicity because most amacrines are sensitive to NMDA in a dose dependent manner and the CaBPs, parvalbumin, (PV); calretinin, (CR); and calbindin (CB) are found in this layer. Exposure of embryonic day 19 chick retina for 60 min to either 25, 100, 250 or 500 micromoles NMDA caused a dose dependent increase in LDH release measured after 24 hr of recovery. At 24 hr, retina was fixed and processed for PV, CR and CB immunoreactivity. The number of amacrine cells positive for the CaBPs were counted and correlated to LDH release. Statistical analysis showed a negative correlation between NMDA mediated LDH release and loss of PV + amacrines and no correlation with loss of CR or CB + amacrines. Thus, as LDH increased, the number of PV cells, but not CB or CR cells declined. Exposure to 500 micromoles NMDA for 24 hr resulted in a near total loss of PV and CB and 66% of CR + amacrines. These data suggest that CB and CR positive amacrine cells show a relative resistance to NMDA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002565-02
Application #
3845349
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code