Yx. Tao et al., Expression of PSD-95/SAP90 is critical for N-methyl-D-aspartate receptor-mediated thermal hyperalgesia in the spinal cord, NEUROSCIENC, 98(2), 2000, pp. 201-206
PSD-95/SAP90, a molecular scaffold protein, attaches the N-methyl-D-asparta
te receptor to cellular signaling pathways through PSD-95/DLG/Z0-1 domain i
nteractions at neuronal synapses.(5,9) This suggests that PSD-95/SAP90 migh
t be involved in many physiological and pathophysiological actions triggere
d via the N-methyl-D-aspartate receptor in the central nervous system. Were
, we present evidence that suppression of the expression of PSD-95/SAP90 in
the spinal cord significantly attenuated facilitation of the tail-hick ref
lex triggered through N-methyl-D-aspartate receptor activation but not base
line tail-flick reflex latency. Moreover, PSD-95/SAP90's messenger RNA and
protein were enriched in the spinal cord and selectively distributed in the
superficial dorsal horn, where PSD-95/SAP90 overlapped with the N-methyl-D
-aspartate receptor. In spinal cord neurons, PSD-95/SAP90 interacted with t
he N-methyl-D-aspartate receptor subunits 2A/2B. It is indicated that activ
ation of the N-methyl-D-aspartate receptor in spinal hyperalgesia results i
n association of the N-methyl-D-aspartate receptor with PSD-95/SAP90 and th
at PSD-95/SAP90 is required for noxious thermal hyperalgesia triggered via
the N-methyl-D-aspartate receptor at the spinal cord level. The present fin
dings may provide novel insights into the mechanisms for persistent sensiti
zation of the somatosensory system. (C) 2000 IBRO. Published by Elsevier Sc
ience Ltd. All rights reserved.