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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

Non-homogeneous distribution of PSD-95 in the human neostriatum. (A,B) Dark-field images of the striatum (A) and lenticular nucleus (B) stained for PSD-95 with DAB. (C,D) Photomicrographs of the caudate nucleus (C) and putamen (D) processed for immunofluorescence staining with anti-PSD-95 antibody. (E,F) Displayed are the caudate nucleus subfield stained for PSD-95 (E), and its graded color-converted image (F), in which labeling intensity is indicated in a standard pseudocolor scale from blue (lowest level) through green, yellow, red, and white (highest level). (G,H) Displayed are the putamen subfield stained for PSD-95 (G), and its graded color-converted image (H), in which labeling intensity is indicated in a standard pseudocolor scale from blue (lowest level) through green, yellow, red, and white (highest level). Asterisks indicate examples of the striatal subfields with sparse PSD-95 immunoreactivity. CN, caudate nucleus; Put, putamen; GPe, globus pallidus externa; GPi; globus pallidus interna. Scale bars: (A,B) 5 mm, (C,D) 2.5 mm, (E–H) 1.5 mm.
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Figure 2: Non-homogeneous distribution of PSD-95 in the human neostriatum. (A,B) Dark-field images of the striatum (A) and lenticular nucleus (B) stained for PSD-95 with DAB. (C,D) Photomicrographs of the caudate nucleus (C) and putamen (D) processed for immunofluorescence staining with anti-PSD-95 antibody. (E,F) Displayed are the caudate nucleus subfield stained for PSD-95 (E), and its graded color-converted image (F), in which labeling intensity is indicated in a standard pseudocolor scale from blue (lowest level) through green, yellow, red, and white (highest level). (G,H) Displayed are the putamen subfield stained for PSD-95 (G), and its graded color-converted image (H), in which labeling intensity is indicated in a standard pseudocolor scale from blue (lowest level) through green, yellow, red, and white (highest level). Asterisks indicate examples of the striatal subfields with sparse PSD-95 immunoreactivity. CN, caudate nucleus; Put, putamen; GPe, globus pallidus externa; GPi; globus pallidus interna. Scale bars: (A,B) 5 mm, (C,D) 2.5 mm, (E–H) 1.5 mm.

Mentions: Our highly sensitive immunohistochemical technique allowed us to detect PSD-95 immunoreactivity in formalin-fixed paraffin-embedded human autopsy tissue. Strong PSD-95 labeling was found in the striatum, consisting of the caudate nucleus, putamen, and nucleus accumbens. Notably, in macroscopic images of the rostral (Figure 2A) and caudal (Figure 2B) parts of the striatum, there was a non-homogeneous distribution of PSD-95 labeling in both the caudate nucleus and putamen. Microscopic images with low-powered magnification also showed the compartmental distribution of PSD-95 labeling in the caudate nucleus (Figure 2C) and putamen (Figure 2D), and this was more evident in the caudate nucleus (Figures 2E,F) than in the putamen (Figures 2G,H). No PSD-95 labeling was identified in striatal sections processed using the immunostaining protocol without the anti-PSD-95 antibody.


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

Morigaki R, Goto S - Front Neuroanat (2015)

Non-homogeneous distribution of PSD-95 in the human neostriatum. (A,B) Dark-field images of the striatum (A) and lenticular nucleus (B) stained for PSD-95 with DAB. (C,D) Photomicrographs of the caudate nucleus (C) and putamen (D) processed for immunofluorescence staining with anti-PSD-95 antibody. (E,F) Displayed are the caudate nucleus subfield stained for PSD-95 (E), and its graded color-converted image (F), in which labeling intensity is indicated in a standard pseudocolor scale from blue (lowest level) through green, yellow, red, and white (highest level). (G,H) Displayed are the putamen subfield stained for PSD-95 (G), and its graded color-converted image (H), in which labeling intensity is indicated in a standard pseudocolor scale from blue (lowest level) through green, yellow, red, and white (highest level). Asterisks indicate examples of the striatal subfields with sparse PSD-95 immunoreactivity. CN, caudate nucleus; Put, putamen; GPe, globus pallidus externa; GPi; globus pallidus interna. Scale bars: (A,B) 5 mm, (C,D) 2.5 mm, (E–H) 1.5 mm.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 2: Non-homogeneous distribution of PSD-95 in the human neostriatum. (A,B) Dark-field images of the striatum (A) and lenticular nucleus (B) stained for PSD-95 with DAB. (C,D) Photomicrographs of the caudate nucleus (C) and putamen (D) processed for immunofluorescence staining with anti-PSD-95 antibody. (E,F) Displayed are the caudate nucleus subfield stained for PSD-95 (E), and its graded color-converted image (F), in which labeling intensity is indicated in a standard pseudocolor scale from blue (lowest level) through green, yellow, red, and white (highest level). (G,H) Displayed are the putamen subfield stained for PSD-95 (G), and its graded color-converted image (H), in which labeling intensity is indicated in a standard pseudocolor scale from blue (lowest level) through green, yellow, red, and white (highest level). Asterisks indicate examples of the striatal subfields with sparse PSD-95 immunoreactivity. CN, caudate nucleus; Put, putamen; GPe, globus pallidus externa; GPi; globus pallidus interna. Scale bars: (A,B) 5 mm, (C,D) 2.5 mm, (E–H) 1.5 mm.
Mentions: Our highly sensitive immunohistochemical technique allowed us to detect PSD-95 immunoreactivity in formalin-fixed paraffin-embedded human autopsy tissue. Strong PSD-95 labeling was found in the striatum, consisting of the caudate nucleus, putamen, and nucleus accumbens. Notably, in macroscopic images of the rostral (Figure 2A) and caudal (Figure 2B) parts of the striatum, there was a non-homogeneous distribution of PSD-95 labeling in both the caudate nucleus and putamen. Microscopic images with low-powered magnification also showed the compartmental distribution of PSD-95 labeling in the caudate nucleus (Figure 2C) and putamen (Figure 2D), and this was more evident in the caudate nucleus (Figures 2E,F) than in the putamen (Figures 2G,H). No PSD-95 labeling was identified in striatal sections processed using the immunostaining protocol without the anti-PSD-95 antibody.

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