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Postsynaptic Density Protein 95 in the Striosome and Matrix Compartments of the Human Neostriatum.

Morigaki R, Goto S - Front Neuroanat (2015)

Bottom Line: This compartment-specific distribution of PSD-95 was strikingly complementary to that of D1R.In addition to the possible involvement of PSD-95-mediated synaptic function in compartment-specific dopamine signals, we suggest that the striosomes might be more susceptible to D1R-mediated neurotoxicity than the matrix compartment.This notion may provide new insight into the compartment-specific vulnerability of MSNs in striatal neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurodegenerative Disorders Research, Institute of Biomedical Sciences, Graduate School of Medical Sciences, Tokushima University Tokushima, Japan ; Parkinson's Disease and Dystonia Research Center, Tokushima University Hospital, Tokushima University Tokushima, Japan ; Department of Neurosurgery, Institute of Biomedical Sciences, Graduate School of Medical Sciences, Tokushima University Tokushima, Japan.

ABSTRACT
The human neostriatum consists of two functional subdivisions referred to as the striosome (patch) and matrix compartments. The striosome-matrix dopamine systems play a central role in cortico-thalamo-basal ganglia circuits, and their involvement is thought to underlie the genesis of multiple movement and behavioral disorders, and of drug addiction. Human neuropathology also has shown that striosomes and matrix have differential vulnerability patterns in several striatal neurodegenerative diseases. Postsynaptic density protein 95 (PSD-95), also known as disks large homolog 4, is a major scaffolding protein in the postsynaptic densities of dendritic spines. PSD-95 is now known to negatively regulate not only N-methyl-D-aspartate glutamate signaling, but also dopamine D1 signals at sites of postsynaptic transmission. Accordingly, a neuroprotective role for PSD-95 against dopamine D1 receptor (D1R)-mediated neurotoxicity in striatal neurodegeneration also has been suggested. Here, we used a highly sensitive immunohistochemistry technique to show that in the human neostriatum, PSD-95 is differentially concentrated in the striosome and matrix compartments, with a higher density of PSD-95 labeling in the matrix compartment than in the striosomes. This compartment-specific distribution of PSD-95 was strikingly complementary to that of D1R. In addition to the possible involvement of PSD-95-mediated synaptic function in compartment-specific dopamine signals, we suggest that the striosomes might be more susceptible to D1R-mediated neurotoxicity than the matrix compartment. This notion may provide new insight into the compartment-specific vulnerability of MSNs in striatal neurodegeneration.

No MeSH data available.


Related in: MedlinePlus

Densitometric analysis on the compartmental distribution of PSD-95 and dopamine D1R in the human neostriatum. (A,B) Line scanning densities of two examples of neostriatal areas double-stained for PSD-95 (green) and D1R (red). The striosome in each image is indicated by a yellow bar. Note that striosomal areas with sparse PSD-95 labeling correspond to those enriched in D1R labeling. Scale bars: 1 mm. (C,D) Measurements of the optical densities of PSD-95- and D1R-immunoreactive products in the striosome (S) and matrix (M) compartments in the caudate nucleus (C) and putamen (D). Data are mean ± SEM (bars) values (n = 25). ∗∗∗P = 0.005, M vs. S; ∗∗P = 0.01, M vs. S.
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Figure 6: Densitometric analysis on the compartmental distribution of PSD-95 and dopamine D1R in the human neostriatum. (A,B) Line scanning densities of two examples of neostriatal areas double-stained for PSD-95 (green) and D1R (red). The striosome in each image is indicated by a yellow bar. Note that striosomal areas with sparse PSD-95 labeling correspond to those enriched in D1R labeling. Scale bars: 1 mm. (C,D) Measurements of the optical densities of PSD-95- and D1R-immunoreactive products in the striosome (S) and matrix (M) compartments in the caudate nucleus (C) and putamen (D). Data are mean ± SEM (bars) values (n = 25). ∗∗∗P = 0.005, M vs. S; ∗∗P = 0.01, M vs. S.

Mentions: To confirm complementary distribution of PSD-95 and D1R, we next carried out a line scanning analysis of the staining density of the neostriatal areas double-stained for PSD-95 and D1R (Figures 6A,B). The results showed that striosomal areas poor in PSD-95 labeling were perfectly matched with those enriched in D1R labeling (Figures 6A,B). Optical density measurements in the caudate nucleus (Figure 6C) and putamen (Figure 6D) revealed that PSD-95 labeling in the striosomes was significantly lower than that in the matrix, while D1R labeling in the striosomes was significantly higher than that in the matrix. Thus, in contrast with that in the matrix compartment, the striosomes were enriched in D1R but showed a paucity of PSD-95.


Postsynaptic Density Protein 95 in the Striosome and Matrix Compartments of the Human Neostriatum.

Morigaki R, Goto S - Front Neuroanat (2015)

Densitometric analysis on the compartmental distribution of PSD-95 and dopamine D1R in the human neostriatum. (A,B) Line scanning densities of two examples of neostriatal areas double-stained for PSD-95 (green) and D1R (red). The striosome in each image is indicated by a yellow bar. Note that striosomal areas with sparse PSD-95 labeling correspond to those enriched in D1R labeling. Scale bars: 1 mm. (C,D) Measurements of the optical densities of PSD-95- and D1R-immunoreactive products in the striosome (S) and matrix (M) compartments in the caudate nucleus (C) and putamen (D). Data are mean ± SEM (bars) values (n = 25). ∗∗∗P = 0.005, M vs. S; ∗∗P = 0.01, M vs. S.
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Related In: Results  -  Collection

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Figure 6: Densitometric analysis on the compartmental distribution of PSD-95 and dopamine D1R in the human neostriatum. (A,B) Line scanning densities of two examples of neostriatal areas double-stained for PSD-95 (green) and D1R (red). The striosome in each image is indicated by a yellow bar. Note that striosomal areas with sparse PSD-95 labeling correspond to those enriched in D1R labeling. Scale bars: 1 mm. (C,D) Measurements of the optical densities of PSD-95- and D1R-immunoreactive products in the striosome (S) and matrix (M) compartments in the caudate nucleus (C) and putamen (D). Data are mean ± SEM (bars) values (n = 25). ∗∗∗P = 0.005, M vs. S; ∗∗P = 0.01, M vs. S.
Mentions: To confirm complementary distribution of PSD-95 and D1R, we next carried out a line scanning analysis of the staining density of the neostriatal areas double-stained for PSD-95 and D1R (Figures 6A,B). The results showed that striosomal areas poor in PSD-95 labeling were perfectly matched with those enriched in D1R labeling (Figures 6A,B). Optical density measurements in the caudate nucleus (Figure 6C) and putamen (Figure 6D) revealed that PSD-95 labeling in the striosomes was significantly lower than that in the matrix, while D1R labeling in the striosomes was significantly higher than that in the matrix. Thus, in contrast with that in the matrix compartment, the striosomes were enriched in D1R but showed a paucity of PSD-95.

Bottom Line: This compartment-specific distribution of PSD-95 was strikingly complementary to that of D1R.In addition to the possible involvement of PSD-95-mediated synaptic function in compartment-specific dopamine signals, we suggest that the striosomes might be more susceptible to D1R-mediated neurotoxicity than the matrix compartment.This notion may provide new insight into the compartment-specific vulnerability of MSNs in striatal neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurodegenerative Disorders Research, Institute of Biomedical Sciences, Graduate School of Medical Sciences, Tokushima University Tokushima, Japan ; Parkinson's Disease and Dystonia Research Center, Tokushima University Hospital, Tokushima University Tokushima, Japan ; Department of Neurosurgery, Institute of Biomedical Sciences, Graduate School of Medical Sciences, Tokushima University Tokushima, Japan.

ABSTRACT
The human neostriatum consists of two functional subdivisions referred to as the striosome (patch) and matrix compartments. The striosome-matrix dopamine systems play a central role in cortico-thalamo-basal ganglia circuits, and their involvement is thought to underlie the genesis of multiple movement and behavioral disorders, and of drug addiction. Human neuropathology also has shown that striosomes and matrix have differential vulnerability patterns in several striatal neurodegenerative diseases. Postsynaptic density protein 95 (PSD-95), also known as disks large homolog 4, is a major scaffolding protein in the postsynaptic densities of dendritic spines. PSD-95 is now known to negatively regulate not only N-methyl-D-aspartate glutamate signaling, but also dopamine D1 signals at sites of postsynaptic transmission. Accordingly, a neuroprotective role for PSD-95 against dopamine D1 receptor (D1R)-mediated neurotoxicity in striatal neurodegeneration also has been suggested. Here, we used a highly sensitive immunohistochemistry technique to show that in the human neostriatum, PSD-95 is differentially concentrated in the striosome and matrix compartments, with a higher density of PSD-95 labeling in the matrix compartment than in the striosomes. This compartment-specific distribution of PSD-95 was strikingly complementary to that of D1R. In addition to the possible involvement of PSD-95-mediated synaptic function in compartment-specific dopamine signals, we suggest that the striosomes might be more susceptible to D1R-mediated neurotoxicity than the matrix compartment. This notion may provide new insight into the compartment-specific vulnerability of MSNs in striatal neurodegeneration.

No MeSH data available.


Related in: MedlinePlus