Postsynaptic Proteins at Excitatory Synapses in the Brain—Relationship with Depressive Disorders
Abstract
:1. Introduction
2. The Role of Postsynaptic Density Proteins in the Excitatory Synapse
3. Alterations in Postsynaptic Density Proteins in Depressive Disorders
3.1. Human Studies
3.2. Animal Studies
4. Postsynaptic Density Proteins as Therapeutic Targets for DDs
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Postsynaptic Proteins | Controls [N] | Patients [N] | Samples/Brain Region | Methods | Findings | Authors’ Names |
---|---|---|---|---|---|---|
NMDA receptor complex | ||||||
GluN1 GluN2A-D GluN3A | N = 19 (male = 18, female = 1) | MDD = 18 male | Locus Coeruleus (LC) Prefrontal Cortex (PFC) | qPCR | ↔GRIN1, GRIN2A mRNA in MDD-LC ↑GRIN2B mRNA in MDD-LC ↔GRIN1, GRIN2A, GRIN2B mRNA in MDD-PFC | Chandley et al. [113] |
GluN1 | N = 15 | MDD = 15 BD = 15 | Prefrontal Cortex | Immunoautoradiography | ↔GluN1 protein in MDD and BD | Toro and Deakin [114] |
GluN1 GluN2A-D | N = 15 | MDD = 15 BD = 15 | Prefrontal Cortex | In situ hybridization | ↓GRIN1 mRNA in MDD and BD ↓GRIN2A mRNA in MDD ↔GRIN2B-D mRNA in MDD ↔GRIN2A-D mRNA in BD | Beneyto and Meador-Woodruff [115] |
GluN1 GluN2A-D GluN3A | N = 20 (male = 11, female = 9) N = 45 (male = 20, female = 25) | MDD = 10 (male = 5, female = 4) BD = 10 (male = 5, female = 5) Suicide = 14 (male = 8, female = 6) | Prefrontal cortex | In situ hybridization | ↑GRIN2D and ↔GRIN1, GRIN2A-C, and GRIN3A mRNA in MDD ↓GRIN2C and ↔GRIN1, GRIN2A, B, D, and GRIN3A mRNA in BD ↓GRIN2B and ↔GRIN1, GRIN2A, C, D and GRIN3A mRNA in Suicides | Dean et al. [116] |
GluN1 GluN2A-B | N = 32 (male = 19, female = 13) MDD-non-suicide (MDD-NS) = 19 (male, female) | MDD = 53 (male = 26, female = 27) MDD-Suicide (MDD-S) = 34 (male, female) | Dorsolateral Prefrontal Cortex | qPCR | ↑GRIN2B, ↔GRIN1 and GRIN2A mRNA in MDD-S-both sexes ↑GRIN1, GRIN2A, GRIN2B mRNA in MDD-female ↑GRIN2B, ↔GRIN1 and GRIN2A mRNA in MDD-S-female ↔GRIN1, GRIN2A and GRIN2B mRNA in male MDD and MDD-S both sexes | Gray et al. [68] |
GluN2A | N = 10 (male) | MDD = 10 (male) | Prefrontal Cortex | Western Blot | ↓GluN2A protein in MDD | Rafalo-Ulinska et al. [74] |
GluN1 GluN2A-B | N = 14 (male = 11, female = 3) | MDD = 14 (male =11, female = 3; 8 male and 2 female were suicides) | Prefrontal Cortex | Western Blot | ↔GluN1 protein in MDD ↓GluN2A, GluN2B protein in MDD | Feyissa et al. [117] |
GluN1 GluN2A-B | N = 14 (male = 13, female = 1) | MDD = 14 (male = 13, female = 1; 12 subjects were suicides) | Lateral amygdala | Western Blot | ↔GluN1, GluN2B protein in MDD ↑GluN2A protein in MDD | Karolewicz et al. [118] |
GluN2A-B | N = 6 | Suicide victims = 17 | Hippocampus | Western Blot | ↑GluN2A protein in suicides ↓GluN2B protein in suicides | Sowa-Kućma et al. [119] |
GluN1 GluN2A-D | N = 18 (female = 7, male = 11) | MDD = 21 (female = 8, male = 13) | Hippocampus: CA1 region (CA1) and Dentate gyrus (DG) | qPCR | ↔GRIN1, GRIN2A-D mRNA in CA1 and DG in MDD—both sexes | Duric et al. [120] |
AMPA receptor complex | ||||||
GluA1-2 | N = 19 (male = 18, female = 1) | MDD = 18 male | Locus Coeruleus (LC) Prefrontal cortex (PFC) | qPCR | ↔GRIA1, GRIA2 mRNA in MDD—LC and PFC | Chandley et al. [113] |
GluA1-2 | N = 32 (male = 19, female = 13) MDD-non-suicide (MDD-NS) = 19 (male, female) | MDD = 53 (male = 26, female = 27) MDD-Suicide (MDD-S) = 34 (male, female) | Dorsolateral Prefrontal Cortex | qPCR | ↑GRIA2 and ↔GRIA1 mRNA in MDD—both sexes ↑GRIA2 and ↔GRIA1 mRNA in MDD-female ↔GRIA1 and GRIA2 mRNA in male MDD and MDD-S | Gray et al. [68] |
GluA1 | N = 10 (male) | MDD = 10 (male) | Prefrontal Cortex | Western Blot | ↓GluA1 protein in MDD | Rafalo-Ulinska et al. [74] |
GluA1-4 | N = 18 (female = 7, male = 11) | MDD = 21 (female = 8, male = 13) | Hippocampus: CA1 region (CA1) and Dentate gyrus (DG) | qPCR | ↓GRIA1 and GRIA3, ↔GRIA2 and GRIA4 mRNA in MDD-both sexes-CA1 and DG | Duric et al. [120] |
Metabotropic glutamate receptor 5 | ||||||
GluR5 | N = 32 (male = 19, female = 13) MDD-non-suicide (MDD-NS) = 19 (male, female) | MDD = 53 (male = 26, female = 27) MDD-Suicide (MDD-S) = 34 (male, female) | Dorsolateral Prefrontal Cortex | qPCR | ↑GRM5 mRNA in MDD-female ↓GRM5 mRNA in MDD—male ↔GRM5 mRNA in MDD-both sexes and MDD-S-both sexes | Gray et al. [68] |
N = 19 (male = 18, female = 1) | MDD = 18 male | Locus Coeruleus (LC) Prefrontal Cortex (PFC) | qPCR | ↑GRM5 mRNA in MDD—LC ↔GRM5 mRNA in MDD—PFC | Chandley et al. [113] | |
Postsynaptic density protein 95 | ||||||
PSD-95 | N = 10 (male) | MDD = 10 (male) | Prefrontal Cortex | Western Blot | ↓PSD-95 protein in MDD | Rafalo-Ulinska et al. [74] |
N = 14 (male = 11, female = 3) | MDD = 14 (male =11, female = 3; 8 male and 2 female were suicides) | Prefrontal Cortex | Western Blot | ↓PSD-95 protein level in MDD | Feyissa et al. [117] | |
N = 14 (male = 13, female = 1) | MDD = 14 (male = 13, female = 1; 12 subjects were suicides) | Lateral amygdala | Western Blot | ↑PSD-95 protein in MDD | Karolewicz et al. [118] | |
N = 6 | Suicide victims = 17 | Hippocampus | Western Blot | ↓PSD-95 protein in suicides | Sowa-Kućma et al. [119] | |
N = 15 | MDD = 15 BD = 15 | Prefrontal Cortex | In situ hybridization | ↔DLG4 mRNA in MDD ↓DLG4 mRNA in BD | Kristiansen and Meador-Woodruff [121] | |
N = 15 | MDD = 15 BD = 15 | Prefrontal Cortex | Immunoautoradiography | ↓PSD-95 protein in BD vs. MDD | Toro and Deakin [114] | |
N = 15 | MDD = 15 BD = 15 | Prefrontal Cortex | In situ hybridization | ↔DLG4 mRNA in MDD and BD | Beneyto and Meador-Woodruff [115] | |
N = 20 (male = 11, female = 9) N = 45 (male = 20, female = 25) | MDD = 10 (male = 5, female = 4) BD = 10 (male = 5, female = 5) Suicide = 14 (male = 8, female = 6) | Prefrontal cortex | Western Blot | ↔ PSD-95 protein in MDD and BD ↓PSD-95 protein in suicides | Dean et al. [116] | |
Zinc transporters | ||||||
ZnT-1 | N = 10 (male) N = 8 (male, female) | MDD = 10 (male) Suicide victims = 11 (male, female) | Prefrontal Cortex | Western Blot | ↑ZnT-1 protein level in MDD and suicides | Rafalo-Ulinska et al. [74] |
Nitric oxide synthases | ||||||
nNOS | N = 27 (controls) N = 27 (first- degree relatives) | MDD = 29 | Neutrophils (venous blood samples) | qPCR | ↑NOS1 mRNA in MDD ↔NOS1 mRNA in first-degree relatives | Somani et al. [99] |
N = 14 (male = 13, female = 1) | MDD = 14 (male = 13, female = 1; 12 subjects were suicides) | Lateral amygdala | Western Blot | ↔nNOS protein in MDD | Karolewicz et al. [118] | |
N = 12 (male = 10, female = 2) | MDD = 12 (male = 9, female = 3; 12 subjects were suicides) | Locus coeruleus (LC) Cerebellum (CER) | Western blot | ↓nNOS protein in MDD-LC ↔nNOS protein in MDD-CER | Karolewicz et al. [122] | |
NOS | N = 895 | MDD = 460 (drug-free = 104; antidepressant group = 356: SSRI = 138; SNRI = 137; another = 81) | Blood plasma | LC-MS | ↓NOS activity (L-Citrulline/L-Arginine ratio) in whole MDD group ↓NOS activity in drug-free MDD ↑NOS activity in whole MDD group at 3 months and 6 months ↑NOS activity in MDD responders group at 3 months and 6 months ↔NOS activity in MDD non-responders group at 3 months and 6 months | Loeb et al. [123] |
SH3 and multiple ankyrin repeat domains 3 | ||||||
Shank3 | No control | MDD = 24 women BD = 32 women (All participants were treated with antidepressants and/or mood stabilizers of the 1st and 2nd generation) | Peripheral blood mononuclear cells (PBMCs) | Microarray | ↑SHANK3 mRNA in MDD after treatment | Dmitrzak-Weglarz et al. [124] |
Postsynaptic Proteins | Species/Strain | Model/Treatment/Groups | Samples/Brain Region | Methods | Findings | Authors’ Names |
---|---|---|---|---|---|---|
NMDA receptor complex | ||||||
NMDAR (no information on subunits) | ICR male mice |
| Hippocampus | qPCR | ↑NMDAR mRNA after CRS, CRS + Zn15, CRS + IMI5 and ↓NMDAR mRNA after CRS + Zn30, CRS + IMI20, and CRS + IMI5 + Zn15 | Ding et al. [125] |
GluN2A | C57BL/6J male mice |
| Infralimbic Cortex (IL), Prelimbic cortex (PL), Basolateral Amygdala (BLA), Lateral Amygdala (LA), Central Amygdala (CEA) CA1 Strata Oriens (OR), CA1 Pyramidal (PYR), CA1 Radiatum (RAD) and CA1 Lacunosum-moleculare layers (LM) | Fluorescence Immunohistochemistry | ↔ GluN2A protein in all brain region after FC + FLU ↑GluN2A protein in BLA, LA, CEA, CA1 PYR after FC+FLU+EXT | Popova et al. [126] |
GluN2A-B | C57Bl/6J male mice |
| Hippocampus (HP) Prefrontal Cortex (PFC) | Western Blot | ↓GluN2A, GluN2B protein after LUR10 and FLU20—HP and PFC | Stan et al. [127] |
GluN2A-B | C57BL/6J male mice |
| Hippocampus (HP) Prefrontal Cortex (PFC) | Western Blot | ↓GluN2A, GluN2B and ↔GluN1 protein level after CUMS—HP ↔GluN1, GluN2A and GluN2B protein after CUMS—PFC ↔GluN2A protein and CUMS + 25 Hz HF-rTMS and ↔GluN2B protein after CUMS+15 Hz HF-rTMS and CUMS + 25 Hz HF-rTMS—HP ↔GluN1, GluN2A, GluN2B protein after CUMS+15 Hz HF-rTMS, CUMS + 25 Hz HF-rTMS | Zuo et al. [128] |
GluN2A-B | C57BL/6J male mice |
| Basolateral Amygdala (BLA) Inferior-Limbic Prefrontal Cortex (IL-PFC) | Western Blot | ↔GluN2A and ↓GluN2B protein in BLA and IL-PFC after KET | Asim et al. [129] |
pS1325-GluN2A pS-1303-GluN2B GluN2A-B GluN1 | C57BL/6J male mice |
| Hippocampus | Western Blot qPCR | ↔GluN1, GluN2A, GluN2B, protein after KET1, 3, 5, 10 ↓GluN2A, GluN2B and ↔GluN1 protein after KET28 ↓GluN2A and GluN2B protein after KET_10 KET_20 and KET_30 pS1325-GluN2A, pS-1303-GluN2B, GluN2A, GluN2B (total, surface, intracellular) protein after KET_30 ↓Grin2A, Grin2B and ↔ Grin1 mRNA after KET_30 | Luo et al. [130] |
GluN2A-B | C57BL/6J female mice |
| Hippocampus | qPCR | ↑Grin2A and Grin2B mRNA after CUS Grin2A and Grin2B mRNA after OVX + CUS ↔Grin2A and ↑Grin2B mRNA after OVX + CUS + P ↑Grin2A and Grin2B mRNA after OVX + CUS+ E | Karisetty et al. [131] |
GluN2B | Swiss male mice |
before each PTZ injection | Prefrontal Cortex (PFC) Hippocampus (HP) | qPCR | ↔Grin2B mRNA level after PTE100, PTE200 + PTZ—PFC ↓Grin2B mRNA after VPA + PTZ—PFC ↔Grin2B mRNA after VPA, PTE100, 200 + PTZ in HP | Nieoczym et al. [132] |
AMPA receptor complex | ||||||
GluA1-pS845 GluA1-3 | CD-1 male mice |
| Prefrontal Cortex—whole tissue lysate Prefrontal Cortex—synaptic fraction | Western Blot | After 60 min of injection: ↔GluA1 and ↑GluA1-pS845 protein after PGM5, 8, 12.5 and IMI ↔GluA2 and GluA3 protein after PGM5, 8, 12.5 and IMI After 5 days of injection: ↑GluA1 protein after PGM 8 and 12.5 and ↑GluA1-pS845protein after PGM5, 8, 12.5 and IMI ↔GluA2 and GluA3 protein after PGM5, 8, 12.5 and IMI After 60 min of injection: ↔GluA1 and ↑GluA1-pS845 protein after PGM5, 8, 12.5 and IMI ↔GluA2 and GluA3 protein after PGM5, 8, 12.5 and IMI After 5 days of injection: ↑GluA1 and GluA1-pS845 protein after PGM5, 8, 12.5 and IMI ↑GluA2 protein after PGM8, 12.5 and IMI ↑GluA3 protein after PGM5, 8, 12.5 and IMI | Bao et al. [133] |
GluA1 | C57BL/6J male mice |
| Hippocampus | Western Blot | ↑GluA1 protein after LPS+KET and LPS +YVAdD ↓GluA1 protein level after LPS ↔GluA1 protein level after LPS+YVAdD+KET | Li et al. [134] |
GluA1 GluA1-pS818 GluA1-pS831 GluA1-pS845 GluA2 GluA2-pS880 | C57BL/6J male mice |
| Medial Prefrontal Cortex | Western Blot | ↔GluA1, ↓GluA1-pS831 and GluA2, and ↔GluA2-pS880 protein after CRS ↔ GluA1-pS818, ↑GluA1-pS831, ↔GluA2 and ↑ GluA2-pS880 after CRS+FLU | Park et al. [135] |
GluA1-2 | C57BL/6J male mice |
| Infralimbic Cortex (IL), Prelimbic cortex (PL), Basolateral Amygdala (BLA), Lateral Amygdala (LA), Central Amygdala (CEA) CA1 Strata Oriens (OR), CA1 Pyramidal (PYR), CA1 Radiatum (RAD) and CA1 Lacunosum-moleculare layers (LM) | Fluorescence Immunohistochemistry | ↓GluA1 protein in CA1 OR after FC+WAT+EXT ↓GluA1 protein in CA1 PYR after FC + FLU + EXT ↑GluA2 protein in all brain region after FC+WAT+EXT and FC+FLU+EXT | Popova et al. [126] |
GluA1 GluA1-pS845 GluA2 | C57BL/6J male mice |
| Basolateral Amygdala | Western Blot | ↑GluA1 and GluA1-pS845, and ↓GluA2 protein after CRS ↑GluA1, ↓GluA1-pS845 and ↑GluA2 protein after CRS + FLU | Yi et al. [136] |
GluA1 GluA1-pS845 | C57BL/6J male mice |
| Western Blot | ↓GluA1 and GluA1-pS845 protein after CUS ↑GluA1 and GluA1-pS845 after CUS + SCO 25 and 50 | Yu et al. [137] | |
GluA1 | Swiss male mice |
| Hippocampus (HP) Prefrontal Cortex (PFC) | Western Blot | ↔ GluA1 protein in Hp after KET5, GUO5 ↓GluA1 protein in HP after CORT, CORT+GUO5 ↑GluA1 protein in HP after CORT+KET ↔GluA1 protein in PFC after KET5, GUO5, CORT, CORT +KET5, CORT + GUO5 ↔GluA1 protein in HP after FLU ↓GluA1 protein in HP after CORT ↓GluA1 protein in HP after CORT+FLU ↔GluA1 protein in PFC after FLU, CORT, CORT + FLU ↔GluA1 protein in HP after KET1+GUO5 ↓GluA1 protein in HP after CORT ↓GluA1 protein in HP after CORT+KET1+GUO5 ↔GluA1 protein in PFC after KET1 +GUO5, CORT, CORT+KET1+GUO5 | Camargo et al. [138] |
GluA1-2 | C57BL/6J male mice |
| Hippocampus | Surface receptor cross-linking with BS3 and Western Blot | ↔GluA1, GluA2 protein in Susceptible and Resilient mice ↓GluA1, GluA2 protein after coss-linking in Susceptible mice | Li et al. [139] |
GluA1-pS845 | C57BL/6J male mice |
| Prefrontal Cortex | Western Blot Fluorescence Immunohistochemistry | ↑GluA1-pS845 protein after NC shRNA+KET ↓GluA1-pS845 protein after VGF shRNA and VGF shRNA+KET ↑GluA1-pS845 protein after NC shRNA+KET ↓GluA1-pS845 protein after VGF shRNA and VGF shRNA+KET | Shen et al. [140] |
GluA1-2 | C57BL/6J male mice |
| Hippocampus | Western Blot | ↓GluA1,GluA2 protein level after CRS, CRS+HNK, CRS+HNK+NBQX, CRS+HNK+ANA-12 | Ju et al. [141] |
pS831-GluA1 pS880-GluA2 GluA1-2 | C57BL/6J male mice |
| Hippocampus | Western BlotqPCR | ↔GluA1,GluA2 protein after KET1, 3, 5, 10 and KET_30 ↓GluA1, GluA2 protein after KET_10, 20 and 30 ↓GluA1,GluA2 after KET.10, KET.20, KET.30 ↓p-S831-GluA1 and p-S880-GluA2 (total, surface, intracellular) protein after KET_30 ↓Gria1, Gria2 mRNA after KET_30 | Luo et al. [130] |
Metabotropic glutamate receptor 5 | ||||||
mGluR5 | C57BL/6J male mice |
| Nucleus Accumbens (NAc) | Western Blot | ↓mGluR5 protein in Susceptible mice ↑mGluR5 protein in Resilient mice | Xu et al. [142] |
C57BL/6J male mice |
| Hippocampus | qPCR | ↑Grm5 mRNA in Susceptible mice ↑Grm5 mRNA after CRS | Li et al. [139] |
Postsynaptic Proteins | Species/Strain | Model/Treatment/Groups | Brain Region | Methods | Findings | Authors’ Names |
---|---|---|---|---|---|---|
NMDA receptor complex | ||||||
GluN2A-B | Sprague Dawley male and female rats |
| Hippocampus | Western blot Post-embedding Immunogold | ↓GluN2A/GluN2B protein in LH compared to NLH ↑GluN2B protein in LH compared to WT ↔GluN2B protein in NLH compared to WT | Bieler et al. [143] |
NMDAR (no information on subunits) | Sprague Dawley male rats |
| Frontal cortex | qPCR | ↓NMDAR mRNA after CUMS ↑NMDAR mRNA n after CUMS+ PAR, CUMS+ Zn+ FA, CUMS+ Zn+ FA+ PAR | Dou et al. [144] |
GluN1 GluN2A pT1325-GluN2A GluN2B pS1303-GluN2B | Sprague Dawley male rats |
| Medial prefrontal cortex (mPFC) | Western blot | ↑GluN1, GluN2B, p-GluN2B and ↔ GluN2A, p-GluN2A protein after CUS ↔GluN2A, p-GluN2A, GluN2B and ↓p-GluN2B protein after CUS+ IFE ↑GluN1 protein after CUS+ IFE ↔GluN1 protein level after CUS+TC-DAPK 6 ↔GluN2B and ↓p-GluN2B protein level after CUS+TC-DAPK 6 ↔GluN1 protein level after CUS+ AAV-shDAPK1 ↔GluN2B protein after CUS+ AAV-shDAPK1 ↓p-GluN2B protein after CUS+ AAV-shDAPK1 | Li et al. [145] |
GluN2A-B | Flinders Sensitive Line (FSL) male rats Flinders Resistant Line (FRL) male rats |
| Hippocampus (HP) Prefrontal cortex (PFC) | Western blot | ↓GluN2A and ↑GluN2B protein in FSL—HP ↔GluN2A and GluN2B protein in FSL—PFC | Treccani et al. [146] |
GluN2A-B | Sprague Dawley male rats |
| Prefrontal cortex (PFC) Hippocampus (HP) Amygdala (AMY) |
Western blot qPCR | ↔GluN2A protein after OB in PFC vs. Sham ↔GluN2A protein after OB+ Mg15 in PFC vs. OB ↔GluN2B protein after OB in PFC vs. Sham ↔GluN2B protein after OB+ Mg15 in PFC vs. OB ↔GluN2A protein after OB in HP vs. Sham ↔GluN2A protein after OB+ Mg15 in HP vs. OB ↔GluN2B protein after OB in HP vs. Sham ↔GluN2B protein after OB+ Mg15 in HP vs. OB ↔GluN2A protein after OB in AMY vs. Sham ↔GluN2A protein after OB+ Mg15 in AMY vs. OB ↔GluN2B protein after OB in AMY vs. Sham ↑GluN2B protein after OB+ Mg15 in AMY vs. OB ↔Grin2A mRNA after OB in PFC vs. Sham ↔Grin2A mRNA after OB+ Mg15 in PFC vs. OB ↔Grin2B mRNA after OB in PFC vs. Sham ↑Grin2B mRNA after OB+ 15 Mg15 in PFC vs. OB ↓Grin2A mRNA after OB in HP vs. Sham ↔Grin2A mRNA after OB+ Mg15 in HP vs. OB ↓Grin2B mRNA after OB in HP vs. Sham ↑Grin2B mRNA after OB+ Mg15 in HP vs. OB | Pochwat et al. [147] |
GluN1 GluN2A-B | Sprague Dawley male rats |
| Hippocampus | Western blot | ↑GluN1, GluN2A and GluN2B proteins after ZnD vs. ZnA ↓GluN1, GluN2A and GluN2B proteins after ZnD+ FLU vs. ZnD | Doboszewska et al. [73] |
GluN2A-B | Sprague Dawley male rats |
| Hippocampus (whole tissue lysate) Hippocampus (synaptoneurosomes) | Western blot | ↓GluN2A and ↔GluN2B protein after CRS ↔ GluN2A, ↔GluN2B protein after CRS+ FAS ↔GluN2A, GluN2B protein after CRS ↔GluN2A, GluN2B protein after CRS+ FAS | Román-Albasini et al. [148] |
GluN2B | Sprague Dawley male rats |
| Hippocampus | Western blot | ↔ GluN2B protein after CUMS ↑GluN2B protein after CUMS+BDNF ↓GluN2B protein after proBDNF | Qiao et al. [149] |
GluN2B | Sprague Dawley male rats |
| Medial prefrontal cortex | Western blot | ↓GluN2B protein after CUMS ↑GluN2B protein after CUMS+ YY-21 ↑GluN2B protein after CUMS+ FLU | Guo et al. [150] |
GluN2A-B | Sprague Dawley male rats |
| Amygdala | Western blot | ↑GluN2A and GluN2B protein after CMS | Zhou et al. [151] |
GluN2A-B | Dark Agouti male rats |
| Frontal cortex | qPCR | ↑Grin2A and Grin2B mRNA after VLX | Tamási et al. [152] |
GluN2B | Sprague Dawley male rats |
| Hippocampus (HP) Nucleus accumbens (NAc) Amygdala (AMY) | Western blot | ↓GluN2B protein after KET in HP ↑GluN2B protein after KET in NAc ↑GluN2B protein after KET in AMY | Piva et al. [153] |
AMPA receptor complex | ||||||
GluA1 | Sprague Dawley male rats |
| Hippocampus (HP) Medial prefrontal cortex (mPFC) | Western blot | ↓GluA1 protein after CUMS and ↑GluA1 protein after CUMS+ IFE in HP ↓GluA1 protein after CUMS and ↑GluA1 protein after CUMS+ IFE in mPFC | Yao et al. [154] |
GluA1 | Sprague Dawley male rats |
| Medial prefrontal cortex | Western blot | ↑GluA1 protein after NVP-AAM077 (only 30 min after administration) | Gordillo-Salas et al. [155] |
GluA1 | Sprague Dawley male rats |
| Medial prefrontal cortex | Western blot | ↓GluA1 protein after CUS ↑GluA1 protein after CUS+IFE | Li et al. [145] |
GluA1 pS831-GluA1 pS845-GluA1 | Sprague Dawley male rats |
| Prefrontal cortex (PFC) Hippocampus (HP) Amygdala (AMY) | Western blot | ↔GluA1, pS831-GluA1, pS845-GluA1 proteins after OB in PFC vs. Sham ↔GluA1,↑pS831-GluA1 and pS845-GluA1 protein after OB+ Mg15 in PFC vs. OB ↔GluA1, pS831-GluA1 and ↑pS845-GluA1 protein after OB in HP vs. Sham ↔GluA1, pS831-GluA1 and ↓pS845-GluA1 protein after OB+ Mg15 in HP vs. OB ↔GluA1, pS831-GluA1 and pS845-GluA1 protein after OB in AMY vs. Sham ↔GluA1, pS831-GluA1 and pS845-GluA1 protein after OB+ Mg15 in AMY vs. OB | Pochwat et al. [147] |
GluA1 pS831-GluA1 pS845-GluA1 GluA2 | Sprague Dawley male rats |
| Hippocampus (whole tissue lysate) Hippocampus (synaptoneurosomes) | Western blot | ↓GluA1 and ↔pS831-GluA1, pS845-GluA1, GluA2 protein level after CRS ↔GluA1, pS831-GluA1, pS845-GluA1, GluA2 protein after CRS+ FAS ↔GluA1, pS831-GluA1, pS845-GluA1, GluA2 protein after CRS ↔GluA1, pS845-GluA1, GluA2 and ↓pS831-GluA1 proteins after CRS+ FAS | Román-Albasini et al. [148] |
GluA3 | Dark Agouti male rats |
| Frontal cortex | qPCR | ↑Gria3 mRNA after VLX | Tamási et al. [152] |
GluA1 | Sprague Dawley male rats |
| Hippocampus | Western blot | ↓GluA1 protein after CUMS ↑GluA1 protein after CUMS+S-KET ↔GluA1 protein after CUMS+ NSC23766 + S-KET ↔GluA1 protein after CUMS + NSC23766 | Zhu et al. [156] |
GluA1 | Sprague Dawley rats |
| Amygdala (AMY) Prefrontal cortex (PFC) | Western blot | ↑GluA1 protein after 3 CS-US in AMY ↔GluA1 protein after 6 CS-US in AMY ↑GluA1 protein after 10 CS-US in AMY ↓GluA1 protein after 10 CS-US+ KET in AMY ↔GluA1 protein after 10 CS-US + FLU in AMY ↓GluA1 protein after 3 CS-US in PFC ↓GluA1 protein after 6 CS-US in PFC ↓GluA1 protein after 10 CS-US in PFC ↑GluA1 protein after 10 CS-US+ KET in PFC ↔GluA1 protein after 10 CS-US + FLU in PFC | Lee et al. [157] |
GluA1 | Sprague Dawley male rats |
| Hippocampus | Western blot | ↓GluA1 protein after CUMS ↑GluA1 protein after CUMS+ VLX ↑GluA1 protein after CUMS+ Dhmc | Yang et al. [158] |
GluA1 pS845-GluA1 | Sprague Dawley male rats |
| Medial prefrontal cortex | Western blot | ↔GluA1 and ↓pS845-GluA1 proteins after CUMS ↔GluA1 and ↑pS845-GluA1 proteins after CUMS+ YY-21 ↔GluA1 and ↑pS845-GluA1 proteins after CUMS+ FLU | Guo et al. [150] |
GluA1 | Sprague Dawley male rats |
| Prefrontal cortex | Western blot | ↔GluA1 protein 30 min after Zn5 treatment ↑GluA1 protein 3 h after Zn5 treatment ↑GluA1 protein 24h after Zn treatment | Szewczyk et al. [159] |
GluA1 pS845-GluA1 | Sprague Dawley male and female rats |
| Hippocampus | Western blot | ↑GluA1 and pS845-GluA1 protein after KET ↔GluA1 and ↑pS845-GluA1 protein after MEM | Zhang et al. [160] |
GluA1 | Sprague Dawley male rats |
| Hypothalamic paraventricular nucleus (hPVN) Hypothalamus (HY) | Western blot qPCR | ↑ GluA1 protein after CUS in hPVN ↑GluA1 protein and ↑Gria1 mRNA after CUS in HY | Li et al. [161] |
GluA1-2 | Sprague Dawley male rats |
| Hippocampus | Western blot | ↓GluA1 and GluA2 protein after CUMS ↑GluA1 protein after CUMS+ NaHS ↑GluA2 protein after CUMS+ NaHS | Hou et al. [162] |
GluA1 | Sprague Dawley male rats |
| Hippocampus (HP) Nucleus accumbens (NAc) Amygdala (AMY) | Western blot | ↓GluA1 protein after KET in HP ↓GluA1 protein after KET in NAc ↔GluA1 protein after KET in AMY | Piva et al. [153] |
Metabotropic glutamate receptor 5 | ||||||
mGluR5 | Sprague Dawley male rats |
| Hippocampus | Western blot Immunohistochemistry qPCR | ↓mGluR5 protein after CUMS ↑mGluR5 protein after CUMS+ FLU ↑mGluR5 protein after CUMS+ SSDH ↑mGluR5 protein after CUMS+ SSDL ↓mGluR5 protein after CUMS ↑mGluR5 protein after CUMS+ FLU ↑mGluR5 protein after CUMS+ SSDH ↑mGluR5 protein after CUMS+ SSDL ↓Grm5 mRNA after CUMS ↑Grm5mRNA after CUMS+ FLU ↑Grm5 mRNA after CUMS+ SSDH ↑Grm5 mRNA after CUMS+ SDDL | Liu et al. [163] |
mGluR5 | Sprague Dawley male rats |
| Hippocampus (HP) Nucleus accumbens (NAc) Amygdala (AMY) | Western blot | ↓mGluR5 protein after KET in HP ↓mGluR5 protein after KET in NAc ↑mGluR5 protein after KET in AMY | Piva et al. [153] |
Postsynaptic Proteins | Species/Strain | Model/Treatment/Groups | Brain Region | Methods | Findings | Authors’ Names |
---|---|---|---|---|---|---|
Postsynaptic density protein 95 | ||||||
PSD-95 | ICR male, female mice |
| Hippocampus—CA1 | Immunofluorescence | ↓PSD-95 protein after KET ↑PSD-95 protein after BET100, KE+BET30 and KE+BET100 | Chen et al. [164] |
Swiss male mice |
| Hippocampus (HP) Prefrontal Cortex (PFC) | Western Blot | ↔PSD-95 protein in HP after KET5, GUO5↓PSD-95 protein in HP after CORT, CORT+GUO5 ↑PSD-95 protein in HP after CORT+KET5 ↔PSD-95 protein in PFC after KET5, GUO5, CORT, CORT+KET5, CORT+GUO5 ↔PSD-95 protein in HP after FLU ↓PSD-95 protein in HP after CORT ↓PSD-95 protein in HP after CORT +FLU ↔PSD-95 protein in PFC after FLU, CORT, CORT + FLU ↔PSD-95 protein in HP after KET1+GUO5 ↓PSD-95 protein in HP after CORT, CORT+KET1+GUO5 ↔PSD-95 protein in PFC after KET1 + GUO5, CORT, CORT + KET1 + GUO5 | Camargo et al. [138] | |
C57BL/6 male mice |
| Basal nuclei (BLA) Lateral nuclei (LAT) Medial Prefrontal Cortex (mPFC) | Immunohistochemistry | ↑PSD-95 protein in LAT and BLA after CRS ↓PSD-95 protein in LAT and BLA after CRS+IMI ↑PSD-95 expression in mPFC after CRS+IMI ↓PSD-95 expression in mPFC after CRS | Leem et al. [165] | |
C57BL/6 male mice |
| Frontal Cortex Hippocampus | Western Blot | ↔PSD-95 protein after CUMS, CUMS + FLU, CUMS+ASI10, 20, 40 ↓PSD-95 protein after CUMS ↑PSD-95 protein after CUMS+ASI10, CUMS + ASI20, CUMS +ASI40, CUMS+FLU | Luo et al. [166] | |
C57Bl/6J male mice |
| Hippocampus (HP) Prefrontal Cortex (PFC) | Western Blot | ↓PSD-95 protein after LUR10 and FLU20 ↓PSD-95 protein after LUR10 and FLU20 | Stan et al. [127] | |
C57Bl/6J male mice |
| Basolateral Amygdala | Western Blot | ↑PSD-95 protein after CRS ↓PSD-95 protein after CRS + FLU | Yi et al. [136] | |
C57BL/6J male mice |
| Hippocampus | Western Blot | ↓PSD-95 protein after CRS, CRS+HNK, CRS+HNK+NBQX, CRS+HNK+ANA-12 | Ju et al. [141] | |
KM (Kunming) male mice |
| Prefrontal Cortex (PFC) Hippocampus (HP) Hypothalamus (HY) Olfactory Bulb (AL) | qPCR Western Blot | ↓Dlg4 mRNA after UCMS, UCMS + Ala2+ Rapa in PFC, HP, Hy, AL. ↑Dlg4mRNA after UCMS+ Ala1 Ala2 in PFC, HP ↔Dlg4 mRNA after UCMS + Ala1 in HY, AL ↑Dlg4 mRNA after UCMS + Ala2 in HY, AL ↓PSD-95 protein after UCMS, UCMS+Ala2+Rapa in PFC ↑PSD-95 protein after UCMS+Ala2 in PFC ↔PSD-95 protein after UCMS+Ala1 in PFC ↓PSD-95 protein after UCMS, UCMS + Ala2 + Rapa in Hp ↑ PSD-95 protein after UCMS+Ala1, Ala2 in Hp ↓PSD-95 protein after UCMS in Hy ↔PSD-95 protein after UCMS + Ala1, Ala2, Ala2 + Rapa in HY ↓PSD-95 protein after UCMS in AL ↑PSD-95 protein after UCMS + Ala2 in AL ↔PSD-95 protein after UCMS + Ala1, Ala2+Rapa | Zhuang et al. [167] | |
Calcium/calmodulin-dependent protein kinase II | ||||||
p-CaMKII | C57BL/6 male mice |
| Basal nuclei (BA) Lateral nuclei (LAT) Medial Prefrontal Cortex (mPFC) | Immunohistochemistry | ↑p-CamKII protein in LAT, BA after CRS and ↓after CRS+IMI ↓p-CamKII protein after CRS in mPFC ↑p-CamKII protein after CRS+IMI in mPFC | Leem et al. [165] |
p-T286-CaMKII t-CaMKII | C57BL/6J male, female mice |
| Prefrontal Cortex | Western Blot | ↓CaMKII-p-T286 and ↔ t-CaMKII protein after SD ↑CaMKII-p-T286 protein after CTM and CTM + SD | Misrani et al. [168] |
CaMKII | ICR male, female mice |
| Hippocampus | Western Blot | ↔CaMKII protein after YG, ES, YG+LPS, ES+LPS (both sexes) ↓CaMKII (female) and ↑CaMKII (male) protein after CUS ↑CaMKII (female) and ↓CaMKII (male) protein after CUS+YG, CUS+ES | Yin et al. [169] |
p-CaMKII (no information about the site of phosphorylation) | ICR male, female mice |
| Hippocampus | Western Blot | ↓p-CAMKII protein after cLH and cLH+YJ (at day 7) ↔ p-CAMKII protein after cLH+FLU (at day 7) ↓p-CAMKII protein after cLH and cLH+FLU (at day 26—after 5 days break in drug administration) | Zou et al. [170] |
p-T286- CaMKII | C57BL/6J male, female mice |
| Hippocampus | Western Blot | ↓p-T286-CAMKII protein after SD ↑p-T286-CAMKII protein after CTM, CTM + SD | Misrani et al. [171] |
CaMKIIα | C57BL/6J male mice |
| Basolateral Amygdala (BLA) Inferior-Limbic Prefrontal Cortex (IL-PFC) | Western Blot | ↔CAMKIIα protein after KET in BLA and IL-PFC | Asim et al. [129] |
Homer scaffold protein 1 | ||||||
Homer 1a | C57BL/6J male mice |
| Hippocampus (HP) Prefrontal Cortex (PFC) | Western Blot | ↓Homer 1a protein in HP and PFC after CUMS ↔Homer 1a protein in HP and PFC after CUMS+15 Hz HF-rTMS, CUMS + 25 Hz HF-rTMS | Zuo et al. [128] |
Homer 1a Homer 1b/c | C57BL/6 female mice |
| Cortex | qPCR | ↓Homer1a and Homer1b/c mRNA expression after CDM ↑Homer1a and Homer1b/c mRNA expression after IMI, FLU, KET | Sun et al. [172] |
Homer 1a Homer 1b/c | C57BL/6 J, CD1 male mice |
| Medial Prefrontal Cortex (mPFC) Hippocampus (HP) Amygdala (AMY) | qPCR Western Blot | ↔Homer1a mRNA in Susceptible, and Resilient mice after CSDS—all brain regions ↑Homer1b/c mRNA in Susceptible mice after CSDS—HP ↔Homer 1a protein in Susceptible and Resilient mice after CSDS—all brain regions ↑Homer 1b/c protein in Susceptible mice after CSDS—HP | Li et al. [139] |
Zinc transporters | ||||||
ZnT-1 | Albino Swiss male mouse |
| Prefrontal Cortex Hippocampus | Western Blot | ↓ZnT-1 protein after Zn ↔ZnT-1 protein after IMI and Zn + IMI ↓ZnT-1 protein after Zn ↔ ZnT-1 protein level after IMI ↑ ZnT-1 protein level after Zn + IMI | Rafało-Ulińska et al. [173] |
Nitric oxide synthases | ||||||
nNOS | ICR male, female mouse |
| Hippocampus | Western Blot | ↔ nNOS protein after YG, ES, YG+LPS, ES+LPS (both sexes) ↓nNOS protein after CUS (female) ↑nNOS protein after CUS+YG, CUS+ES (female) ↑nNOS protein after CUS (male) ↓nNOS protein after CUS+YG, CUS+ES (male) | Yin et al. [169] |
Postsynaptic Proteins | Species/Strain | Model/Treatment | Brain Region | Methods | Findings | Authors’ Names |
---|---|---|---|---|---|---|
Postsynaptic density protein 95 | ||||||
PSD-95 | Sprague Dawley male rats |
| Medial prefrontal cortex | Western blot | ↓PSD-95 protein after CUS ↑PSD-95 protein after CUS+ IFE | Li et al. [145] |
Sprague Dawley male rats |
| Hippocampus (CA1 and CA3 region) Dentate gyrus | Western blot | ↓PSD-95 protein after CUMS in all regions ↑PSD-95 protein after CUMS+ NaHS in all regions | Hou et al. [162] | |
Sprague Dawley male rats |
| Hypothalamus | Western blot qPCR | ↑PSD-95 protein after CUS ↑Dlg4 mRNA after CUS | Li et al. [161] | |
Sprague Dawley male rats |
| Medial prefrontal cortex | Western blot | ↑PSD-95 protein after CX717 (only 2 h after administration) | Gordillo-Salas et al. [174] | |
Sprague Dawley male rats |
| Hippocampus | Western blot | ↓PSD-95 protein after CUMS ↑PSD-95 protein after CUMS+ S-KET ↑PSD-95 protein after CUMS+ NSC23766 + S-KET ↑PSD-95 protein after CUMS+ NSC23766 | Zhu et al. [156] | |
Sprague Dawley male rats |
| Amygdala (AMY) Prefrontal cortex (PFC) | Western blot | ↑PSD-95 protein after 3 CS-US in AMY ↔PSD-95 protein after 6 CS-US in AMY ↑PSD-95 protein after 10 CS-US in AMY ↔PSD-95 protein after 10 CS-US+ KET in AMY ↔PSD-95 protein after 10 CS-US+ FLU in AMY ↓PSD-95 protein after 3 CS-US in PFC ↓PSD-95 protein after 6 CS-US in PFC ↓PSD-95 protein after 10 CS-US in PFC ↑PSD-95 protein after 10 CS-US+ KET in PFC ↔PSD-95 protein after 10 CS-US + FLU in PFC | Lee et al. [157] | |
Sprague Dawley male rats |
| Medial prefrontal cortex | Western blot | ↓PSD-95 protein after CUMS ↑PSD-95 protein after CUMS+ YY-21 ↔PSD-95 protein after CUMS+ FLU | Guo et al. [150] | |
Sprague Dawley male rats |
| Prefrontal cortex | Western blot | ↔PSD95 protein 30min after Zn treatment ↑PSD95 protein level 3 h after Zn treatment ↔PSD95 protein level 24h after Zn treatment | Szewczyk et al. [159] | |
Wistar male rats |
| Prefrontal cortex | qPCR | ↓Dlg4 mRNA after CMS (stress-reactive group) ↑Dlg4mRNA after CMS+ LUR | Luoni et al. [175] | |
PSD-95 | Sprague Dawley male rats |
| Hippocampus | Western blot Immunohistochemistry qPCR | ↓PSD-95 protein after CUMS ↑PSD95 protein CUMS+ FLU ↑PSD95 protein CUMS+ SDDH ↔PSD95 protein CUMS+ SDDL ↓PSD-95 protein after CUMS ↑PSD95 protein CUMS+ FLU ↑PSD95 protein CUMS+ SDDH ↔PSD95 protein CUMS+ SDDL ↓Dlg4 mRNA after CUMS ↑Dlg4 mRNA after CUMS+ FLU ↑Dlg4 mRNA after CUMS+ SDDH ↑Dlg4 mRNA after CUMS+ SDDL | Liu et al. [163] |
Calcium/calmodulin-dependent protein kinase II | ||||||
CaMKII p-T286-CaMKII p-T286-CaMKIIα p-T286-CaMKIIβ | Sprague Dawley male rats |
| Hippocampus | Western blot | ↔CaMKII protein after CUMS ↔CaMKII protein after CUMS+ GXDSF in all groups ↑p-CaMKII protein after CUMS ↓p-CaMKII protein after CUMS+ GXDSF in all groups ↑p-CaMKIIα protein after CUMS ↓p-CaMKIIα protein after CUMS+ GXDSF in all groups ↑p-CaMKIIβ protein after CUMS ↓ p-CaMKIIβ protein after CUMS+ GXDSF in all groups | Xie et al. [176] |
CaMKIIγ CaMKIIβ | Dark Agouti male rats |
| Frontal cortex | qPCR | ↑Camk2g mRNA after VLX ↑Camk2b mRNA after VLX | Tamási et al. [152] |
Homer scaffold protein 1 | ||||||
Homer 1 | Wistar male rats |
| Prefrontal cortex | Western blot | ↑Homer1 protein in resilient group compared to anhedonic | Palmfeldt et al. [177] |
Homer 1 | Sprague Dawley male rats |
| Hippocampus (synaptoneurosomes) | Western blot | ↔Homer1 protein after CRS ↔Homer1 protein after CRS+ FAS | Román-Albasini et al. [148] |
Homer 1 | Sprague Dawley male rats |
| Hippocampus | Western blot Immunohistochemistry qPCR | ↑Homer1b/c protein after CUMS ↓Homer-1b/c protein after CUMS+ FLU ↓Homer1b/c protein after CUMS+ SSDH ↓Homer1b/c protein after CUMS+ SSDL ↑Homer1b/c protein after CUMS ↓Homer1b/c protein after CUMS+ FLU ↓Homer1b/c protein after CUMS+ SSDH ↓Homer1b/c protein after CUMS+ SSDL ↑Homer1 mRNA after CUMS ↓Homer1 mRNA after CUMS+ FLU ↓Homer1 mRNA after CUMS+ SDDH ↓Homer1 mRNA after CUMS+ SDDL | Liu et al. [163] |
Nitric oxide synthases | ||||||
nNOS iNOS eNOS | Wistar male rats |
| Cerebellum (CER) Frontal cortex (FC) Midbrain (MID) Olfactory bulb (OB) Pons Striatum Temporal cortex (TC) Thalamus (TH) Hippocampus (HP) | qPCR | ↔Nos1 mRNA after AR ↔Nos1 mRNA after AR+ FLU, AR+MIL, AR+MIR—all brain regions ↑Nos2 mRNA after AR—CER, FC, MID, OB, pons, striatum, TC, TH ↔Nos2 mRNA after AR—HP ↔Nos2 mRNA after AR+ FLU, AR+MIL, AR+MIR—all brain regions ↔Nos3 mRNA after AR ↑Nos3 mRNA after AR+ FLU—CER, Hp, midbrain, pons, striatum, thalamus, FC ↔Nos3 mRNA after AR+ FLU—OB, TC; after AR+ MIL and AR+ MIR—all brain regions | Yoshino et al. [178] |
nNOS | Sprague Dawley male rats |
| Hippocampus | Western blot | ↑nNOS protein after CUS ↓nNOS protein after CUS + MEM | Mishra et al. [179] |
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Samojedny, S.; Czechowska, E.; Pańczyszyn-Trzewik, P.; Sowa-Kućma, M. Postsynaptic Proteins at Excitatory Synapses in the Brain—Relationship with Depressive Disorders. Int. J. Mol. Sci. 2022, 23, 11423. https://doi.org/10.3390/ijms231911423
Samojedny S, Czechowska E, Pańczyszyn-Trzewik P, Sowa-Kućma M. Postsynaptic Proteins at Excitatory Synapses in the Brain—Relationship with Depressive Disorders. International Journal of Molecular Sciences. 2022; 23(19):11423. https://doi.org/10.3390/ijms231911423
Chicago/Turabian StyleSamojedny, Sylwia, Ewelina Czechowska, Patrycja Pańczyszyn-Trzewik, and Magdalena Sowa-Kućma. 2022. "Postsynaptic Proteins at Excitatory Synapses in the Brain—Relationship with Depressive Disorders" International Journal of Molecular Sciences 23, no. 19: 11423. https://doi.org/10.3390/ijms231911423