The in vivo synaptic plasticity mechanism of EGb 761-induced enhancement of spatial learning and memory in aged rats - PubMed (original) (raw)

The in vivo synaptic plasticity mechanism of EGb 761-induced enhancement of spatial learning and memory in aged rats

Yongfu Wang et al. Br J Pharmacol. 2006 May.

Abstract

It has not been uniform to date that the Ginkgo biloba extracts enhance cognitive function in aged animals, and the mechanisms of action remain difficult to elucidate. In this study, the Morris water maze task and electrophysiological methods were used to study the effects of repeated daily administration of EGb 761, a standardized extract from G. biloba leaves, on hippocampal-dependent spatial learning and memory and synaptic plasticity of aged rats. The adult subjects perform the Morris water maze task better than aged rats, as a cellular mechanism, the hippocampal long-term potentiation (LTP) elicited from adult animals is robust (139.29+/-2.7%). In addition, the spatial learning and memory of aged rats that had been fed on an EGb 761-supplemented diet (60 mg kg(-1)) for 30 days were significantly better than those of control aged rats. The magnitude of LTP (116.63+/-3.6%) recorded in vivo from the hippocampus CA1 area of aged rats was significantly enhanced by EGb 761 (60 mg kg(-1)). In conclusion, the spatial learning and memory of aged rats is worse than that of young subjects, and EGb 761, acting as a 'cognitive enhancer', has benefit on synaptic plasticity and cognition in aged rats. The present data further confirmed that enhancement of synaptic plasticity of the hippocampus might ameliorate the deficit in spatial learning and memory in aged rats.

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Figures

Figure 1

Figure 1

The spatial learning and memory was impaired concomitant with aging in the classic Morris water maze tasks. (a) The escape latency in the Morris water maze of Y-VEH adult rats (_n_=8) was shorter than that of the VEH aged group (_n_=8) (##P<0.01). Animals in the VEH group did not reach the criterion for finding the platform in 30 s. (b) The swim speed of VEH aged animals was significantly slower than Y-VEH rats (#P<0.05, ##P<0.01). (c) The distance of Y-VEH adult rats was shorter than that of the VEH aged group (_n_=8) (##P<0.01). (d) The time spent in the OP of Y-VEH animals was significantly shorter compared with that in the TA on the probe test day in which the platform was removed from water maze ($P<0.05), and the searching time at TA of Y-VEH animals was also significantly longer than that of VEH aged rats (##P<0.01). The data were presented as mean±s.e.m. of each session.

Figure 2

Figure 2

Repeated daily administration of EGb 761 improved the spatial learning and memory in the classic Morris water maze tasks in aged rats. (a) The escape latency in the water maze of animals administered EGb 761 at a dose of 60 mg kg−1 (_n_=8), not 30 mg kg−1 (_n_=8), was shorter than that of the VEH group (_n_=8) (*P<0.05, **_P_<0.01 vs VEH). Animals in the VEH group did not reach the criterion for finding the platform in 30 s. (b) The swimming speed of aged animals was not affected by EGb 761 (_P_>0.05). (c) The distance of EGb 761 (60 mg kg−1) group animals was significantly shorter than that of VEH animals on training days 3 and 4 (*P<0.05, **P<0.01 vs VEH). (d) The searching time of EGb 761 (60 mg kg−1) group animals was significantly longer in the TA than that in the OP on the probe test day in which the platform was removed from water maze ($$P<0.01), and the searching time at TA of EGb 761 (60 mg kg−1) group animals was also significantly longer than that of VEH animals (*P<0.05). The data were presented as mean±s.e.m. of each session.

Figure 3

Figure 3

Improvement of repeated-reversal spatial learning and memory in the Platform-switched Morris water maze task by EGb 761. (a) Animals administered either 30 (_n_=8) or 60 mg kg−1 (_n_=8) EGb 761 spent less time finding the location of the switched platform than control animals (*P<0.05, **_P_<0.01). (b) EGb 761 did not affect the motor activation of aged rats as the swim speeds of the VEH and EGb 761 groups showed no significant difference (_P_>0.05). The data were presented as mean±s.e.m. of each session.

Figure 4

Figure 4

The visual acuity of aged rats was not affected by EGb 761. The time spent finding a visible marker platform did not show a significant difference between the VEH (_n_=8) and EGb 761 groups (_n_=16) (_P_>0.05). The data were presented as mean±s.e.m. of each trial.

Figure 5

Figure 5

EGb 761 enhanced the augmentation of hippocampal LTP in the CA1 area of aged rats. (a) The LTP of the hippocampus of Y-VEH adult rats was large compared with baseline after HFS (139.29±2.7%, _n_=5, P<0.01, down triangle). (b) The changes of hippocampal fEPSP of VEH aged rats were unreliable after HFS compared with baseline (101.11±2.3%, _n_=5, open square). (c) The LTP of the hippocampus of aged rats in the EGb 761 (60 mg kg−1) group was obvious compared with baseline after HFS (116.63±3.6%, _n_=6, _P_<0.01, down triangle). (d) The magnitude of hippocampal fEPSP in the EGb 761 (30 mg kg−1) group showed no significant changes compared with baseline after HFS (97.98±4.2%, _n_=5, up triangle), and there was no significant difference between EGb 761 (30 mg kg−1) and VEH in the amplitude changes of fEPSP following HFS (_P_>0.05 vs VEH).

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