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[Involvement of protein tyrosine kinases in β-amyloid protein-induced suppression of long-term potentiation in the rat hippocampal CA1 region in vivo.] [Ariticle in Chinese]

GUO Fen, LI Xin-Yi, WANG Xiao-Hui, QI Jin-Shun^*

Department of Physiology, and the Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan 030001, China

Abstract

Although the impairing effects of β-amyloid (Aβ) protein on synaptic plasticity and cognitive function have been widely reported, the mechanisms underlying the neurotoxicity of Aβ are still not well known. The present study observed the effects of intracerebroventricular (i.c.v.) injection of both Aβ25-35 and genistein (a specific tyrosine kinase inhibitor at high concentration) on the hippocampal long-term potentiation (LTP) in the CA1 region, and investigated its possible protein tyrosine kinase (PTK) mechanism. Male Wistar rats were surgically prepared for acute LTP recordings in vivo. Two parallel bond electrodes for stimulating and recording were simultaneously inserted into the right hippocampus of rats. The field excitatory postsynaptic potentials (fEPSPs), paired-pulse facilitation (PPF) and high-frequency stimuli (HFS)-induced LTP were recorded by delivering test stimuli, paired pulses and HFS to the Schaffer-collateral/commissural pathway. The results showed that: (1) i.c.v. injection of Aβ25-35 did not affect the baseline synaptic transmission, but significantly suppressed the HFS-induced LTP, with a decreased average amplitude of fEPSPs [(129.2±6.7)% in 10 nmol Aβ25-35 group; (110.6±8.6)% in 20 nmol Aβ25-35 group; P<0.01] at 1 h post-HFS when compared to that in the control group [(163.1±8.1)%]; (2) Similarly, i.c.v. injection of genistein (200 nmol) did not change the basic synaptic transmission, but significantly suppressed HFS-induced LTP, with the similar average amplitude of fEPSPs [(114.0±7.2)%] at 1 h post-HFS to that in 20 nmol Aβ25-35 group; (3) Co-application of Aβ25-35 (20 nmol) and genistein (200 nmol) caused no additive suppression of LTP, and the average amplitude of fEPSPs was (113.0±8.8)% at 1 h post-HFS, showing no significant difference when compared with that in Aβ25-35 or genistein alone groups (P>0.05); (4) There was no significant change in the PPF following genistein and Aβ25-35 alone or co-injection (P> 0.05). These experimental results indicate that i.c.v. injection of Aβ25-35 can significantly suppress the HFS-induced LTP in the CA1 area of rat hippocampus in vivo, implying that the Aβ deposited in the brain of patients with Alzheimer’s disease may impair the function of learning and memory by suppressing the hippocampal LTP. The facts that the extent of inhibition of Aβ25-35 and genistein on LTP was similar and no further potentiation of the suppression was observed when Aβ25-35 and genistein were co-applied suggest that PTK is probably involved in the Aβ-induced suppression of hippocampal LTP.

Key words: protein tyrosine kinases; amyloid beta-protein; field excitatory postsynaptic potential; long-term potentiation; hippocampus

Received: 2008-12-19　　Accepted: 2009-03-04

Corresponding author: 祁金顺　　E-mail: jinshunqi2006@yahoo.com

Citing This Article：

GUO Fen, LI Xin-Yi, WANG Xiao-Hui, QI Jin-Shun. [Involvement of protein tyrosine kinases in β-amyloid protein-induced suppression of long-term potentiation in the rat hippocampal CA1 region in vivo.] [Ariticle in Chinese] . Acta Physiol Sin 2009; 61 (3): 263-271 (in Chinese with English abstract).