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Updated: May 28, 2026
Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
CD200 fusion protein decreases microglial activation in the hippocampus of aged rats
F Fionnuala Cox1, Donal Carney, Anne-Marie Miller
1Trinity College Institute for Neuroscience, Department of Physiology, Trinity College, Dublin 2, Ireland.
Abstract:
The glycoprotein, CD200, is primarily expressed on neurons and its cognate receptor CD200R is expressed principally on cells of the myeloid lineage, including microglia. The interaction of CD200 with its receptor plays a significant role in maintaining microglia in a quiescent state and therefore a decrease in CD200 expression in brain is associated with evidence of microglial activation. Conversely, activation of CD200R, for example using a CD200 fusion protein (CD200Fc), should result in a decrease in microglial activation. Here we assessed the effect of delivery of CD200Fc intrahippocampally on microglial activation and on long-term potentiation (LTP) in perforant path-granule cell synapses in young and aged rats. We hypothesized that the age-related changes in microglial activation would be attenuated by CD200Fc resulting in an improved ability of aged rats to sustain LTP. The data indicate that expression of markers of microglial activation including major histocompatibility complex Class II (MHCII) and CD40 mRNA, as well as MHCII immunoreactivity, were increased in hippocampus of aged, compared with young, rats and that these changes were associated with a deficit in LTP; these changes were attenuated in hippocampal tissue prepared from aged rats which received CD200Fc. Microglial activation and a deficit in LTP have also been reported in lipopolysaccharide (LPS)-treated rats and, here, we report that these changes were also attenuated in CD200Fc-treated animals. Thus the negative impact of microglial activation on the ability of aged and LPS-treated rats to sustain LTP is ameliorated when CD200R is activated by CD200Fc.
Insights
Activating CD200 receptor (CD200R) with CD200Fc reduces microglial activation in aged rats. This treatment improves long-term potentiation (LTP) in the hippocampus, counteracting age-related deficits.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- CD200 glycoprotein on neurons interacts with CD200 receptor (CD200R) on microglia.
- This interaction maintains microglial quiescence; reduced CD200 expression correlates with microglial activation.
- Microglial activation and impaired synaptic plasticity, like long-term potentiation (LTP), are observed in aging and under inflammatory conditions.
Purpose of the Study:
- To investigate the effect of intrahippocampal CD200Fc delivery on microglial activation and LTP in young and aged rats.
- To determine if CD200Fc can attenuate age-related microglial activation and improve synaptic function.
- To assess if CD200Fc can ameliorate microglial activation and LTP deficits induced by lipopolysaccharide (LPS).
Main Methods:
- Administration of CD200Fc intrahippocampally in young, aged, and LPS-treated rats.
- Assessment of microglial activation markers (MHCII, CD40 mRNA, MHCII immunoreactivity) in hippocampal tissue.
- Measurement of long-term potentiation (LTP) at perforant path-granule cell synapses.
Main Results:
- Aged rats exhibited increased hippocampal microglial activation markers and impaired LTP compared to young rats.
- CD200Fc treatment attenuated these age-related increases in microglial activation and improved LTP.
- CD200Fc treatment also reduced microglial activation and LTP deficits in LPS-treated rats.
Conclusions:
- Activation of CD200R by CD200Fc effectively reduces microglial activation in the hippocampus.
- CD200Fc treatment ameliorates age-related deficits in synaptic plasticity (LTP).
- CD200Fc represents a potential therapeutic strategy to counteract detrimental effects of microglial activation in aging and inflammation.
