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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

Identification of postsynaptic density protein 95 (PSD-95) in the mouse striatum. (A) Western blot assay. Crude homogenates of protein (10 μg) from the mouse striatum were separated on a 10% gel by SDS-PAGE and then immunoblotted using anti-PSD-95 antibody. Note that an immunostained protein band (arrow) was selectively detected, with an approximate molecular mass corresponding to the predicted size of native PSD-95 protein. PS, protein staining; IB, immunoblot. (B) Photomicrograph of a striatal section stained for PSD-95. (C–E) Photomicrographs of the dorsal striatum stained for PSD-95 in the absence (C,E) and presence (D) of DAPI (4′,6-diamidino-2-phenylindole)-staining. Tiny dots immunoreactive for PSD-95 (inset in D,E) are numerously found in the dorsal striatum. (F) Photomicrograph of the dorsal striatum processed using the immunostaining protocol without anti-PSD-95 antibody. Scale bars: (B) 1 mm, (C,D,F) 50 μm, (inset in D) 5 μm, (E) 2.5 μm.
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Figure 1: Identification of postsynaptic density protein 95 (PSD-95) in the mouse striatum. (A) Western blot assay. Crude homogenates of protein (10 μg) from the mouse striatum were separated on a 10% gel by SDS-PAGE and then immunoblotted using anti-PSD-95 antibody. Note that an immunostained protein band (arrow) was selectively detected, with an approximate molecular mass corresponding to the predicted size of native PSD-95 protein. PS, protein staining; IB, immunoblot. (B) Photomicrograph of a striatal section stained for PSD-95. (C–E) Photomicrographs of the dorsal striatum stained for PSD-95 in the absence (C,E) and presence (D) of DAPI (4′,6-diamidino-2-phenylindole)-staining. Tiny dots immunoreactive for PSD-95 (inset in D,E) are numerously found in the dorsal striatum. (F) Photomicrograph of the dorsal striatum processed using the immunostaining protocol without anti-PSD-95 antibody. Scale bars: (B) 1 mm, (C,D,F) 50 μm, (inset in D) 5 μm, (E) 2.5 μm.

Mentions: To confirm the specificity of the anti-PSD-95 antibody used here, we first carried out a western-blot analysis of the mouse brains. A protein band with an approximate molecular mass corresponding to the predicted size of native PSD-95 protein was selectively detected on the immunoblots of mouse striatal extracts (Figure 1A). The specificity of staining was also determined on frozen sections from mouse brains with or without anti-PSD-95 antibody (Figures 1B–F). Strong immunoreactivity for PSD-95 was found in the striatum (Figure 1B), where numerous tiny immunoreactive dots were densely distributed (Figures 1C–E). According to the previous reports (Kim and Sheng, 2004; van Zundert et al., 2004), we suppose that the vast majority of them were localized in the PSDs of dendritic spines of striatal neurons. No immunoreactivity for PSD-95 was found in striatal sections processed using the immunostaining protocol without the anti-PSD-95 antibody (Figure 1F). Notably, no apparent compartmental localization of PSD-95 labeling in the mouse striatum could be detected (Figure 1B). A knockout control for specificity of reactivity in immunohistological experiments was not done.


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

Morigaki R, Goto S - Front Neuroanat (2015)

Identification of postsynaptic density protein 95 (PSD-95) in the mouse striatum. (A) Western blot assay. Crude homogenates of protein (10 μg) from the mouse striatum were separated on a 10% gel by SDS-PAGE and then immunoblotted using anti-PSD-95 antibody. Note that an immunostained protein band (arrow) was selectively detected, with an approximate molecular mass corresponding to the predicted size of native PSD-95 protein. PS, protein staining; IB, immunoblot. (B) Photomicrograph of a striatal section stained for PSD-95. (C–E) Photomicrographs of the dorsal striatum stained for PSD-95 in the absence (C,E) and presence (D) of DAPI (4′,6-diamidino-2-phenylindole)-staining. Tiny dots immunoreactive for PSD-95 (inset in D,E) are numerously found in the dorsal striatum. (F) Photomicrograph of the dorsal striatum processed using the immunostaining protocol without anti-PSD-95 antibody. Scale bars: (B) 1 mm, (C,D,F) 50 μm, (inset in D) 5 μm, (E) 2.5 μm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Identification of postsynaptic density protein 95 (PSD-95) in the mouse striatum. (A) Western blot assay. Crude homogenates of protein (10 μg) from the mouse striatum were separated on a 10% gel by SDS-PAGE and then immunoblotted using anti-PSD-95 antibody. Note that an immunostained protein band (arrow) was selectively detected, with an approximate molecular mass corresponding to the predicted size of native PSD-95 protein. PS, protein staining; IB, immunoblot. (B) Photomicrograph of a striatal section stained for PSD-95. (C–E) Photomicrographs of the dorsal striatum stained for PSD-95 in the absence (C,E) and presence (D) of DAPI (4′,6-diamidino-2-phenylindole)-staining. Tiny dots immunoreactive for PSD-95 (inset in D,E) are numerously found in the dorsal striatum. (F) Photomicrograph of the dorsal striatum processed using the immunostaining protocol without anti-PSD-95 antibody. Scale bars: (B) 1 mm, (C,D,F) 50 μm, (inset in D) 5 μm, (E) 2.5 μm.
Mentions: To confirm the specificity of the anti-PSD-95 antibody used here, we first carried out a western-blot analysis of the mouse brains. A protein band with an approximate molecular mass corresponding to the predicted size of native PSD-95 protein was selectively detected on the immunoblots of mouse striatal extracts (Figure 1A). The specificity of staining was also determined on frozen sections from mouse brains with or without anti-PSD-95 antibody (Figures 1B–F). Strong immunoreactivity for PSD-95 was found in the striatum (Figure 1B), where numerous tiny immunoreactive dots were densely distributed (Figures 1C–E). According to the previous reports (Kim and Sheng, 2004; van Zundert et al., 2004), we suppose that the vast majority of them were localized in the PSDs of dendritic spines of striatal neurons. No immunoreactivity for PSD-95 was found in striatal sections processed using the immunostaining protocol without the anti-PSD-95 antibody (Figure 1F). Notably, no apparent compartmental localization of PSD-95 labeling in the mouse striatum could be detected (Figure 1B). A knockout control for specificity of reactivity in immunohistological experiments was not done.

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