Limits...
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

Complementary distribution of dopamine D1 receptor (D1R) and PSD-95 in striatal compartments of the human neostriatum. (A,B) Photomicrographs of the caudate nucleus double-stained for D1R (A) and PSD-95 (B). Examples of striosomes are indicated by asterisks. (C–E) Photomicrographs of the putamen double-stained for D1R (C) and PSD-95 (D), with a merged image (E). Examples of the corresponding striosomes are indicated by asterisks. (F–H) Photomicrographs showing a border area between the striosome and matrix compartment in the striatal section double-stained for D1R (F) and PSD-95 (G), with a merged image (H). (I,J) Photomicrographs of the striosome (I) and matrix (J) areas stained for D1R. (K–M) Photomicrographs of the striosomal area double-stained for D1R (K) and PSD-95 (L), with a merged image (M). Dashed open circles indicate examples of medium-sized cells possessing both D1R and PSD-95 labeling in their soma. Scale bars: (A–E) 2 mm, (F–H) 200 μm, (I–M) 50 μm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4663261&req=5

Figure 5: Complementary distribution of dopamine D1 receptor (D1R) and PSD-95 in striatal compartments of the human neostriatum. (A,B) Photomicrographs of the caudate nucleus double-stained for D1R (A) and PSD-95 (B). Examples of striosomes are indicated by asterisks. (C–E) Photomicrographs of the putamen double-stained for D1R (C) and PSD-95 (D), with a merged image (E). Examples of the corresponding striosomes are indicated by asterisks. (F–H) Photomicrographs showing a border area between the striosome and matrix compartment in the striatal section double-stained for D1R (F) and PSD-95 (G), with a merged image (H). (I,J) Photomicrographs of the striosome (I) and matrix (J) areas stained for D1R. (K–M) Photomicrographs of the striosomal area double-stained for D1R (K) and PSD-95 (L), with a merged image (M). Dashed open circles indicate examples of medium-sized cells possessing both D1R and PSD-95 labeling in their soma. Scale bars: (A–E) 2 mm, (F–H) 200 μm, (I–M) 50 μm.

Mentions: In agreement with the previous reports (Besson et al., 1988; Levey et al., 1993), we found a compartmental distribution for D1R immunoreactivity in the human neostriatum, with higher labeling density in the striosomes than in the matrix. As determined by double immunofluorescence staining, D1R labeling was strikingly complementary to that of PSD-95 in both the caudate nucleus (Figures 5A,B) and putamen (Figures 5C–E). At higher-power magnification, the margins of the PSD-95-poor zones appeared to closely correspond with the outer margins of the D1R-rich zones (Figures 5F–H). At higher-powered magnification, D1R-immunoreactive products were found abundantly in the striosomes (Figure 5I), but less so in the matrix (Figure 5J). Striosomal MSNs possessing both D1R and PSD-95 labeling in their soma are shown in Figures 5K–M.


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

Morigaki R, Goto S - Front Neuroanat (2015)

Complementary distribution of dopamine D1 receptor (D1R) and PSD-95 in striatal compartments of the human neostriatum. (A,B) Photomicrographs of the caudate nucleus double-stained for D1R (A) and PSD-95 (B). Examples of striosomes are indicated by asterisks. (C–E) Photomicrographs of the putamen double-stained for D1R (C) and PSD-95 (D), with a merged image (E). Examples of the corresponding striosomes are indicated by asterisks. (F–H) Photomicrographs showing a border area between the striosome and matrix compartment in the striatal section double-stained for D1R (F) and PSD-95 (G), with a merged image (H). (I,J) Photomicrographs of the striosome (I) and matrix (J) areas stained for D1R. (K–M) Photomicrographs of the striosomal area double-stained for D1R (K) and PSD-95 (L), with a merged image (M). Dashed open circles indicate examples of medium-sized cells possessing both D1R and PSD-95 labeling in their soma. Scale bars: (A–E) 2 mm, (F–H) 200 μm, (I–M) 50 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663261&req=5

Figure 5: Complementary distribution of dopamine D1 receptor (D1R) and PSD-95 in striatal compartments of the human neostriatum. (A,B) Photomicrographs of the caudate nucleus double-stained for D1R (A) and PSD-95 (B). Examples of striosomes are indicated by asterisks. (C–E) Photomicrographs of the putamen double-stained for D1R (C) and PSD-95 (D), with a merged image (E). Examples of the corresponding striosomes are indicated by asterisks. (F–H) Photomicrographs showing a border area between the striosome and matrix compartment in the striatal section double-stained for D1R (F) and PSD-95 (G), with a merged image (H). (I,J) Photomicrographs of the striosome (I) and matrix (J) areas stained for D1R. (K–M) Photomicrographs of the striosomal area double-stained for D1R (K) and PSD-95 (L), with a merged image (M). Dashed open circles indicate examples of medium-sized cells possessing both D1R and PSD-95 labeling in their soma. Scale bars: (A–E) 2 mm, (F–H) 200 μm, (I–M) 50 μm.
Mentions: In agreement with the previous reports (Besson et al., 1988; Levey et al., 1993), we found a compartmental distribution for D1R immunoreactivity in the human neostriatum, with higher labeling density in the striosomes than in the matrix. As determined by double immunofluorescence staining, D1R labeling was strikingly complementary to that of PSD-95 in both the caudate nucleus (Figures 5A,B) and putamen (Figures 5C–E). At higher-power magnification, the margins of the PSD-95-poor zones appeared to closely correspond with the outer margins of the D1R-rich zones (Figures 5F–H). At higher-powered magnification, D1R-immunoreactive products were found abundantly in the striosomes (Figure 5I), but less so in the matrix (Figure 5J). Striosomal MSNs possessing both D1R and PSD-95 labeling in their soma are shown in Figures 5K–M.

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