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CX(3)CR1 deficiency alters hippocampal-dependent plasticity phenomena blunting the effects of enriched environment.

Maggi L, Scianni M, Branchi I, D'Andrea I, Lauro C, Limatola C - Front Cell Neurosci (2011)

Bottom Line: At this aim wt and CX(3)CR1(GFP/GFP) mice were exposed to long-lasting-enriched environment (EE) and the effects on hippocampal functions were studied by electrophysiological recordings of long-term potentiation of synaptic activity, behavioral tests of learning and memory in the Morris water maze paradigm and analysis of neurogenesis in the subgranular zone of the dentate gyrus (DG).We found that CX(3)CR1 deficiency increases hippocampal plasticity and spatial memory, blunting the potentiating effects of EE.These data indicate that CX(3)CL1/CX(3)CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Università di Roma Rome Italy.

ABSTRACT
In recent years several evidence demonstrated that some features of hippocampal biology, like neurogenesis, synaptic transmission, learning, and memory performances are deeply modulated by social, motor, and sensorial experiences. Fractalkine/CX(3)CL1 is a transmembrane chemokine abundantly expressed in the brain by neurons, where it modulates glutamatergic transmission and long-term plasticity processes regulating the intercellular communication between glia and neurons, being its specific receptor CX(3)CR1 expressed by microglia. In this paper we investigated the role of CX(3)CL1/CX(3)CR1 signaling on experience-dependent hippocampal plasticity processes. At this aim wt and CX(3)CR1(GFP/GFP) mice were exposed to long-lasting-enriched environment (EE) and the effects on hippocampal functions were studied by electrophysiological recordings of long-term potentiation of synaptic activity, behavioral tests of learning and memory in the Morris water maze paradigm and analysis of neurogenesis in the subgranular zone of the dentate gyrus (DG). We found that CX(3)CR1 deficiency increases hippocampal plasticity and spatial memory, blunting the potentiating effects of EE. In contrast, exposure to EE increased the number and migration of neural progenitors in the DG of both wt and CX(3)CR1(GFP/GFP) mice. These data indicate that CX(3)CL1/CX(3)CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.

No MeSH data available.


Related in: MedlinePlus

Neuronal precursors in the DG of wt and CX3CR1GFP/GFP mice. (A) Representative low-scale magnification of mouse hippocampal dentate gyrus (DG) coronal section stained for Hoechst (blue). The highlight square illustrates the DG regions amplified in (B–E) where DCX+ cells are shown. Scale bar, 100 μm. (B–E) Representative images of DCX+ cells (red) in the DG of wt and CX3CR1GFP/GFP mice, in SE and EE as indicated. Migrating DCX+ cells are marked with white arrows, non-migrating cells with yellow arrows. Green cells in CX3CR1GFP/GFP slice are microglia. Scale bar, 10 μm. (F) Histograms showing the number of DCX+ cells square millimeter in the DG of wt (left) and CX3CR1GFP/GFP mice (right) in SE (top) and EE (bottom). *Is EE vs. SE and $ is CX3CR1GFP/GFP vs. wt. (p < 0.001). (G) Migrating DCX+ cells square millimeter in the DG of wt and CX3CR1GFP/GFP mice in SE and EE. *Is EE vs. SE and $ is CX3CR1GFP/GFP vs. wt. (p < 0.001). (H) Histograms showing the ratio between migrating vs. total DCX+ in wt and CX3CR1GFP/GFP mice in SE and EE. *Is EE vs. SE (p < 0.001) and # is within SE CX3CR1GFP/GFP vs. wt. (p < 0.05). Data are presented as mean ± SEM.
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Figure 4: Neuronal precursors in the DG of wt and CX3CR1GFP/GFP mice. (A) Representative low-scale magnification of mouse hippocampal dentate gyrus (DG) coronal section stained for Hoechst (blue). The highlight square illustrates the DG regions amplified in (B–E) where DCX+ cells are shown. Scale bar, 100 μm. (B–E) Representative images of DCX+ cells (red) in the DG of wt and CX3CR1GFP/GFP mice, in SE and EE as indicated. Migrating DCX+ cells are marked with white arrows, non-migrating cells with yellow arrows. Green cells in CX3CR1GFP/GFP slice are microglia. Scale bar, 10 μm. (F) Histograms showing the number of DCX+ cells square millimeter in the DG of wt (left) and CX3CR1GFP/GFP mice (right) in SE (top) and EE (bottom). *Is EE vs. SE and $ is CX3CR1GFP/GFP vs. wt. (p < 0.001). (G) Migrating DCX+ cells square millimeter in the DG of wt and CX3CR1GFP/GFP mice in SE and EE. *Is EE vs. SE and $ is CX3CR1GFP/GFP vs. wt. (p < 0.001). (H) Histograms showing the ratio between migrating vs. total DCX+ in wt and CX3CR1GFP/GFP mice in SE and EE. *Is EE vs. SE (p < 0.001) and # is within SE CX3CR1GFP/GFP vs. wt. (p < 0.05). Data are presented as mean ± SEM.

Mentions: CX3CR1GFP/GFP mice do not have evident alterations in brain development (Jung et al., 2000) but show decreased proliferation and neurogenesis in the SGZ and granular layer of the DG (Bachstetter et al., 2011). In order to investigate if the differences in learning and memory abilities observed in CX3CR1GFP/GFP mice could be correlated with alterations in DG neurogenesis, we analyzed the number of neuronal precursors (DCX positive cells) present in the DG of wt and CX3CR1GFP/GFP mice grown in SE or EE (n = 4 for both housing conditions and genotypes) (representative image shown in Figure 4A). We reported that the number of neuronal precursors was affected not only by the lack of CX3CR1, as shown by the significant effect of genotype [F(1,13) = 28.327, p < 0.001], but also by the housing conditions [F(1,13) = 19,238, p < 0.001] without any significant interaction between the two factors (p = 0.760). The mean area values of the DG analyzed for wt and CX3CR1GFP/GFP mice were not significantly different, indicating that the effect of genotype was not dependent on different DG size (wt: 0.143 mm ± 0.004 mm, CX3CR1GFP/GFP: 0.141 mm ± 0.004 mm). Post hoc analysis revealed that the number of DCX positive cells was: (i) significantly higher in wt compared to CX3CR1GFP/GFP (p < 0.001; Figure 4B–F , as previously described (Bachstetter et al., 2011); (ii) increased by exposure to EE in both genotypes (p < 0.001; Figures 4D–F).


CX(3)CR1 deficiency alters hippocampal-dependent plasticity phenomena blunting the effects of enriched environment.

Maggi L, Scianni M, Branchi I, D'Andrea I, Lauro C, Limatola C - Front Cell Neurosci (2011)

Neuronal precursors in the DG of wt and CX3CR1GFP/GFP mice. (A) Representative low-scale magnification of mouse hippocampal dentate gyrus (DG) coronal section stained for Hoechst (blue). The highlight square illustrates the DG regions amplified in (B–E) where DCX+ cells are shown. Scale bar, 100 μm. (B–E) Representative images of DCX+ cells (red) in the DG of wt and CX3CR1GFP/GFP mice, in SE and EE as indicated. Migrating DCX+ cells are marked with white arrows, non-migrating cells with yellow arrows. Green cells in CX3CR1GFP/GFP slice are microglia. Scale bar, 10 μm. (F) Histograms showing the number of DCX+ cells square millimeter in the DG of wt (left) and CX3CR1GFP/GFP mice (right) in SE (top) and EE (bottom). *Is EE vs. SE and $ is CX3CR1GFP/GFP vs. wt. (p < 0.001). (G) Migrating DCX+ cells square millimeter in the DG of wt and CX3CR1GFP/GFP mice in SE and EE. *Is EE vs. SE and $ is CX3CR1GFP/GFP vs. wt. (p < 0.001). (H) Histograms showing the ratio between migrating vs. total DCX+ in wt and CX3CR1GFP/GFP mice in SE and EE. *Is EE vs. SE (p < 0.001) and # is within SE CX3CR1GFP/GFP vs. wt. (p < 0.05). Data are presented as mean ± SEM.
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Figure 4: Neuronal precursors in the DG of wt and CX3CR1GFP/GFP mice. (A) Representative low-scale magnification of mouse hippocampal dentate gyrus (DG) coronal section stained for Hoechst (blue). The highlight square illustrates the DG regions amplified in (B–E) where DCX+ cells are shown. Scale bar, 100 μm. (B–E) Representative images of DCX+ cells (red) in the DG of wt and CX3CR1GFP/GFP mice, in SE and EE as indicated. Migrating DCX+ cells are marked with white arrows, non-migrating cells with yellow arrows. Green cells in CX3CR1GFP/GFP slice are microglia. Scale bar, 10 μm. (F) Histograms showing the number of DCX+ cells square millimeter in the DG of wt (left) and CX3CR1GFP/GFP mice (right) in SE (top) and EE (bottom). *Is EE vs. SE and $ is CX3CR1GFP/GFP vs. wt. (p < 0.001). (G) Migrating DCX+ cells square millimeter in the DG of wt and CX3CR1GFP/GFP mice in SE and EE. *Is EE vs. SE and $ is CX3CR1GFP/GFP vs. wt. (p < 0.001). (H) Histograms showing the ratio between migrating vs. total DCX+ in wt and CX3CR1GFP/GFP mice in SE and EE. *Is EE vs. SE (p < 0.001) and # is within SE CX3CR1GFP/GFP vs. wt. (p < 0.05). Data are presented as mean ± SEM.
Mentions: CX3CR1GFP/GFP mice do not have evident alterations in brain development (Jung et al., 2000) but show decreased proliferation and neurogenesis in the SGZ and granular layer of the DG (Bachstetter et al., 2011). In order to investigate if the differences in learning and memory abilities observed in CX3CR1GFP/GFP mice could be correlated with alterations in DG neurogenesis, we analyzed the number of neuronal precursors (DCX positive cells) present in the DG of wt and CX3CR1GFP/GFP mice grown in SE or EE (n = 4 for both housing conditions and genotypes) (representative image shown in Figure 4A). We reported that the number of neuronal precursors was affected not only by the lack of CX3CR1, as shown by the significant effect of genotype [F(1,13) = 28.327, p < 0.001], but also by the housing conditions [F(1,13) = 19,238, p < 0.001] without any significant interaction between the two factors (p = 0.760). The mean area values of the DG analyzed for wt and CX3CR1GFP/GFP mice were not significantly different, indicating that the effect of genotype was not dependent on different DG size (wt: 0.143 mm ± 0.004 mm, CX3CR1GFP/GFP: 0.141 mm ± 0.004 mm). Post hoc analysis revealed that the number of DCX positive cells was: (i) significantly higher in wt compared to CX3CR1GFP/GFP (p < 0.001; Figure 4B–F , as previously described (Bachstetter et al., 2011); (ii) increased by exposure to EE in both genotypes (p < 0.001; Figures 4D–F).

Bottom Line: At this aim wt and CX(3)CR1(GFP/GFP) mice were exposed to long-lasting-enriched environment (EE) and the effects on hippocampal functions were studied by electrophysiological recordings of long-term potentiation of synaptic activity, behavioral tests of learning and memory in the Morris water maze paradigm and analysis of neurogenesis in the subgranular zone of the dentate gyrus (DG).We found that CX(3)CR1 deficiency increases hippocampal plasticity and spatial memory, blunting the potentiating effects of EE.These data indicate that CX(3)CL1/CX(3)CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Università di Roma Rome Italy.

ABSTRACT
In recent years several evidence demonstrated that some features of hippocampal biology, like neurogenesis, synaptic transmission, learning, and memory performances are deeply modulated by social, motor, and sensorial experiences. Fractalkine/CX(3)CL1 is a transmembrane chemokine abundantly expressed in the brain by neurons, where it modulates glutamatergic transmission and long-term plasticity processes regulating the intercellular communication between glia and neurons, being its specific receptor CX(3)CR1 expressed by microglia. In this paper we investigated the role of CX(3)CL1/CX(3)CR1 signaling on experience-dependent hippocampal plasticity processes. At this aim wt and CX(3)CR1(GFP/GFP) mice were exposed to long-lasting-enriched environment (EE) and the effects on hippocampal functions were studied by electrophysiological recordings of long-term potentiation of synaptic activity, behavioral tests of learning and memory in the Morris water maze paradigm and analysis of neurogenesis in the subgranular zone of the dentate gyrus (DG). We found that CX(3)CR1 deficiency increases hippocampal plasticity and spatial memory, blunting the potentiating effects of EE. In contrast, exposure to EE increased the number and migration of neural progenitors in the DG of both wt and CX(3)CR1(GFP/GFP) mice. These data indicate that CX(3)CL1/CX(3)CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.

No MeSH data available.


Related in: MedlinePlus