Article

Effects of 56Fe radiation on hippocampal function in mice deficient in chemokine receptor 2 (CCR2)

Departments of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA
Behavioural brain research (Impact Factor: 3.03). 03/2013; 246(1). DOI: 10.1016/j.bbr.2013.03.003
Source: PubMed

ABSTRACT

(56)Fe irradiation affects hippocampus-dependent cognition. The underlying mechanisms may involve alterations in neurogenesis, expression of the plasticity-related immediate early gene Arc, and inflammation. Chemokine receptor-2 (CCR2), which mediates the recruitment of infiltrating and resident microglia to sites of CNS inflammation, is upregulated by (56)Fe irradiation. CCR2 KO and wild-type mice were used to compare effects of (56)Fe radiation (600 MeV, 0.25Gy) on hippocampal function using contextual fear conditioning involving tone shock pairing during training (+/+) and exposure to the same environment without tone shock pairings (-/-). In the -/- condition, irradiation enhanced habituation in WT mice, but not CCR2 KO mice, suggesting that a lack of CCR2 was associated with reduced cognitive performance. In the++ condition, irradiation reduced freezing but there was no genotype differences. There were no significant correlations between the number of Arc-positive cells in the dentate gyrus and freezing in either genotype. While measures of neurogenesis and gliogenesis appeared to be modulated by CCR2, there were no effects of genotype on the total numbers of newly born activated microglia before or after irradiation, indicating that other mechanisms are involved in the genotype-dependent radiation response.

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    • "There are thus various reports in which CCR2 expressing cells are suggested to be microglia (Abbadie et al., 2003; Zhang et al., 2007; Fernández-López et al., 2012) or described as microglia/macrophages (Yao and Tsirka, 2012) or referred to as amoeboid microglia cells (Deng et al., 2009). Often CCR2 is discussed to be an important receptor for the recruitment of microglia to injured brain areas (El Khoury et al., 2007; Zhang et al., 2007; Deng et al., 2009; Raber et al., 2013) and in this respect CCR2 has been described as receptor in spinal cord microglia that enables these cells to respond to peripheral nerve injury (Abbadie et al., 2003; Zhang et al., 2007). "
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    • " protect against loss of dopaminer - gic neurons in the striatum ( Kalkonde et al . , 2007 ) . More recently , CCR2 deficiency was shown to prevent hippocampus - dependent spatial learning and memory impair - ments induced by cranial irradiation , highlighting the poten - tial neuron - specific functions of this receptor ( Belarbi et al . , 2013 ; Raber et al . , 2013 ) . These contrasting views might be explained by alternative ligands , besides CCL2 : binding and signaling through CCR2 can be achieved by CCL2 , CCL7 , CCL8 , CCL12 , and CCL13 ( Bose and Cho , 2013 ) . For example , CCL8 was reported to elicit the CCR2 - mediated neuroprotective effects after irradiation ( Belarbi et al . , 2013 ) ."
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    • "On one hand there are various reports in which CCR2 expressing cells are suggested to be microglia (Abbadie et al., 2003; Zhang et al., 2007; Fernández-López et al., 2012) or described as microglia/macrophages (Yao and Tsirka, 2012) or referred to as amoeboid microglia cells (Deng et al., 2009). Often CCR2 is discussed to be an important receptor for the recruitment of microglia to injured brain areas (El Khoury et al., 2007; Zhang et al., 2007; Deng et al., 2009; Raber et al., 2013) and the inhibition or lack of CCR2 signaling is related to improved disease outcome (Abbadie et al., 2003; Dimitrijevic et al., 2007; Zhang et al., 2007; Fernández-López et al., 2012; Yao and Tsirka, 2012) implicating that CCR2-expressing microglia at least contribute to disease progression. "
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