Inhibition of long-term potentiation development in rat hippocampal slice by α2-macroglobulin, an acute-phase protein in the brain
✍ Scribed by I. Çavuş; P.H. Koo; T.J. Teyler
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 690 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Alpha-2-macroglobulin (a,M) in the rat and human brain is an acute-phase protein synthesized primarily by astrocytes, and it has been implicated in Alzheimer's disease and other neuropathological processes. The activated forms of aZM, but not the native form, can suppress the neurite outgrowth of the central neurons, presumably through binding to neurotrophic factors and through direct inhibition of neurotrophic factor receptor signal transduction. Since neurotrophic factors are known to be involved in synaptic plasticity, we tested the effect of both the native and methylamine-activated (MA-a,M) forms of a,M on long-term potentiation (LTP) in area CA1 of adult rat hippocampal slice. Neither native a,M nor MA-a,M had an effect on baseline synaptic transmission. LTP induced by 200-Hz trains in the presence of 1.4 p M or 0.14 pM native a,M was indistinguishable from control LTP. Although the presence of MA-a,M at the same concentrations did not interfere with LTP induction, the development and maintenance of potentiation was blocked in a concentration-dependent time course. Results of this study indicate that the accumulation and activation of a,M with inflammatory neuropathologies such as Alzheimer's disease can inhibit synaptic plasticity, which might partly account for the memory deficits seen in these patients.