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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

Somatic labeling for PSD-95 in the medium spiny neurons (MSNs) in the human neostriatum. (A,B) Photomicrographs of the matrix (A) and striosome (B) subfields in the striatal section stained for PSD-95. Neurons with somatic labeling for PSD-95 are indicated by dashed open circles. Note that somatic density of PSD-95 labeling in matrix cells is higher than that in striosomal cells. (C–E) Photomicrographs of the matrix area double-stained for DARPP-32, a marker protein for striatal MSNs (C) and PSD-95 (D), with a merged image (E). (F–H) Photomicrographs of the striosome area double-stained for DARPP-32 (F) and PSD-95 (G), with a merged image (H). (I–K) Photomicrographs of an MSN in the matrix area double-stained for DARPP-32 (I) and PSD-95 (J), with a merged image (K). The proximal dendrite and soma of the labeled cell are indicated by small and large arrows, respectively. (L) Measurements of the optical densities of somatic PSD-95 labeling of striosomal (S) MSNs and matrix (M) MSNs in the caudate nucleus (CN) and putamen (Put). Data are mean ± SEM (bars) values (n = 100). ∗∗p = 0.01, ∗p = 0.05, Matrix (M) MSNs vs. Striosomal (S) MSNs. Scale bars: (A,B) 20 μm, (C–H) 50 μm, (I–K) 10 μm.
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Figure 4: Somatic labeling for PSD-95 in the medium spiny neurons (MSNs) in the human neostriatum. (A,B) Photomicrographs of the matrix (A) and striosome (B) subfields in the striatal section stained for PSD-95. Neurons with somatic labeling for PSD-95 are indicated by dashed open circles. Note that somatic density of PSD-95 labeling in matrix cells is higher than that in striosomal cells. (C–E) Photomicrographs of the matrix area double-stained for DARPP-32, a marker protein for striatal MSNs (C) and PSD-95 (D), with a merged image (E). (F–H) Photomicrographs of the striosome area double-stained for DARPP-32 (F) and PSD-95 (G), with a merged image (H). (I–K) Photomicrographs of an MSN in the matrix area double-stained for DARPP-32 (I) and PSD-95 (J), with a merged image (K). The proximal dendrite and soma of the labeled cell are indicated by small and large arrows, respectively. (L) Measurements of the optical densities of somatic PSD-95 labeling of striosomal (S) MSNs and matrix (M) MSNs in the caudate nucleus (CN) and putamen (Put). Data are mean ± SEM (bars) values (n = 100). ∗∗p = 0.01, ∗p = 0.05, Matrix (M) MSNs vs. Striosomal (S) MSNs. Scale bars: (A,B) 20 μm, (C–H) 50 μm, (I–K) 10 μm.

Mentions: Compared with the striosomes, the matrix compartment was more strongly stained for PSD-95, as determined using serial sections stained for PSD-95 (Figure 3A) and Calbindin-D28K (Figure 3B), a protein enriched in the matrix of the human striatum (Ito et al., 1992). Double immunofluorescence staining also showed that PSD-95 immunoreactivity was sparse in striosomes that exhibited low calbindin labeling (Figures 3C–E). At higher-powered magnification, PSD-95-immunoreactive dots were found abundantly in the matrix (Figure 3F), but less so in the striosomes (Figure 3G). Thus, PSD-95 was differentially concentrated in the striosome-matrix systems of the human neostriatum, with higher density of PSD-95 in the matrix relative to the striosomes. In addition, PSD-95 appeared as not only a dendritic but also a somatic protein in striosomal and matrix MSNs (Figure 4), as determined using sections double-stained for PSD-95 and DARPP-32, a marker of MSNs (Langley et al., 1997). In both the caudate nucleus and putamen, the mean somatic density of PSD-95 labeling in striosomal MSNs was significantly lower than that in matrix MSNs (Figure 4L). This finding suggests that PSD-95 might be abundantly expressed in the matrix MSNs, whereas low levels of PSD-95 expression were observed in the striosomal MSNs.


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

Morigaki R, Goto S - Front Neuroanat (2015)

Somatic labeling for PSD-95 in the medium spiny neurons (MSNs) in the human neostriatum. (A,B) Photomicrographs of the matrix (A) and striosome (B) subfields in the striatal section stained for PSD-95. Neurons with somatic labeling for PSD-95 are indicated by dashed open circles. Note that somatic density of PSD-95 labeling in matrix cells is higher than that in striosomal cells. (C–E) Photomicrographs of the matrix area double-stained for DARPP-32, a marker protein for striatal MSNs (C) and PSD-95 (D), with a merged image (E). (F–H) Photomicrographs of the striosome area double-stained for DARPP-32 (F) and PSD-95 (G), with a merged image (H). (I–K) Photomicrographs of an MSN in the matrix area double-stained for DARPP-32 (I) and PSD-95 (J), with a merged image (K). The proximal dendrite and soma of the labeled cell are indicated by small and large arrows, respectively. (L) Measurements of the optical densities of somatic PSD-95 labeling of striosomal (S) MSNs and matrix (M) MSNs in the caudate nucleus (CN) and putamen (Put). Data are mean ± SEM (bars) values (n = 100). ∗∗p = 0.01, ∗p = 0.05, Matrix (M) MSNs vs. Striosomal (S) MSNs. Scale bars: (A,B) 20 μm, (C–H) 50 μm, (I–K) 10 μm.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 4: Somatic labeling for PSD-95 in the medium spiny neurons (MSNs) in the human neostriatum. (A,B) Photomicrographs of the matrix (A) and striosome (B) subfields in the striatal section stained for PSD-95. Neurons with somatic labeling for PSD-95 are indicated by dashed open circles. Note that somatic density of PSD-95 labeling in matrix cells is higher than that in striosomal cells. (C–E) Photomicrographs of the matrix area double-stained for DARPP-32, a marker protein for striatal MSNs (C) and PSD-95 (D), with a merged image (E). (F–H) Photomicrographs of the striosome area double-stained for DARPP-32 (F) and PSD-95 (G), with a merged image (H). (I–K) Photomicrographs of an MSN in the matrix area double-stained for DARPP-32 (I) and PSD-95 (J), with a merged image (K). The proximal dendrite and soma of the labeled cell are indicated by small and large arrows, respectively. (L) Measurements of the optical densities of somatic PSD-95 labeling of striosomal (S) MSNs and matrix (M) MSNs in the caudate nucleus (CN) and putamen (Put). Data are mean ± SEM (bars) values (n = 100). ∗∗p = 0.01, ∗p = 0.05, Matrix (M) MSNs vs. Striosomal (S) MSNs. Scale bars: (A,B) 20 μm, (C–H) 50 μm, (I–K) 10 μm.
Mentions: Compared with the striosomes, the matrix compartment was more strongly stained for PSD-95, as determined using serial sections stained for PSD-95 (Figure 3A) and Calbindin-D28K (Figure 3B), a protein enriched in the matrix of the human striatum (Ito et al., 1992). Double immunofluorescence staining also showed that PSD-95 immunoreactivity was sparse in striosomes that exhibited low calbindin labeling (Figures 3C–E). At higher-powered magnification, PSD-95-immunoreactive dots were found abundantly in the matrix (Figure 3F), but less so in the striosomes (Figure 3G). Thus, PSD-95 was differentially concentrated in the striosome-matrix systems of the human neostriatum, with higher density of PSD-95 in the matrix relative to the striosomes. In addition, PSD-95 appeared as not only a dendritic but also a somatic protein in striosomal and matrix MSNs (Figure 4), as determined using sections double-stained for PSD-95 and DARPP-32, a marker of MSNs (Langley et al., 1997). In both the caudate nucleus and putamen, the mean somatic density of PSD-95 labeling in striosomal MSNs was significantly lower than that in matrix MSNs (Figure 4L). This finding suggests that PSD-95 might be abundantly expressed in the matrix MSNs, whereas low levels of PSD-95 expression were observed in the striosomal MSNs.

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