[Correlation of changes of peripheral benzodiazepine receptors in hippocampus synaptosomes with cognitive impairment: experiment with D-galactose-induced senescent rats].
OBJECTIVE
To investigate the effects of peripheral benzodiazepine receptor (PBR) in hippocampus synaptosomes on spatial learning and memory.


METHODS
Twenty-four Sprague-Dawley rats of both sexes were randomly divided into 2 equal groups: D-galactose-treated group, receiving subcutaneous injection of D-galactose 100 mg/kg once a day for 56 days, and normal saline (NS) control group, receiving comparable injections of NS. Spatial learning and memory were assessed by Morris water maze test for 5 days. After the behavioral testing all rats were decapitated and the hippocampus was removed immediately. Then, the synaptosomes in hippocampus were purified by density gradient centrifugation. The PBR binding parameters, maximal binding site density (B(max)) and equilibrium dissociation constant (KD), were estimated by radioligand [(3)H] PK11195 binding assays.


RESULTS
Two weeks after the beginning of experiment the D-galactose-treated rats began to show symptoms of aging. On the 5th day of behavioral testing the D-galactose-induced aging rats presented significant impairment in water maze performance compared with the NS controls (P < 0.001). The decrease in specific [(3)H] PK11195 binding in the hippocampus synaptosomes of the D-galactose-treated group was 67.3 +/- 18.6 fmol/mg, significantly lower than that of the saline control group (127.9 +/- 20.1 fmol/mg, P < 0.01). The Scatchard analysis revealed that the B(max) of the D-galactose-treated group was 177.2 +/- 26.7 fmol/mg, significantly lower than that of the saline group (296.7 +/- 33.5 fmol/mg, P < 0.01), and the K(D) of the D-galactose-treated group was 0.503 +/- 0.06 nmol/L, not significantly different from that of the saline control group (0.502 +/- 0.05 nmol/L). Correlation analysis showed that the specific [(3)H] PK11195 binding in hippocampus synaptosomes was closely related to the escaping latency (r = -0.854), swimming time (r = 0.845), and distance (r = 0.851) in platform quadrant in Morris water maze in all rats (all P < 0.001).


CONCLUSIONS
The decreased expression of PBR in hippocampus synaptosomes is possibly associated with the spatial learning-memory impairments induced by D-galactose.
Chen
Chun-fu
CF
Department of Neurology, General Hospital of the People's Liberation Army, Beijing 100853, China.
Lang
Sen-yang
SY
Zuo
Ping-ping
PP
Wang
Xiang-qing
XQ
Yang
Nan
N
D000375:Aging / Q000187:drug effects*; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism*; D005690:Galactose; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007858:Learning / Q000187:drug effects; D008569:Memory Disorders / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
D011963:Receptors, GABA-A; D005690:Galactose