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. 2022 Sep 28;23(19):11423. doi: 10.3390/ijms231911423

Table 4.

Summary of studies on the expression of postsynaptic density proteins in mouse models of depression and/or after antidepressants treatment.

Postsynaptic Proteins Species/Strain Model/Treatment/Groups Brain Region Methods Findings Authors’ Names
Postsynaptic density protein 95
PSD-95 ICR male, female mice

  • Ketamine 20 mg/kg i,p. 14 days (twice a day) (KET)

  • Betaine 0, 30, 100 mg/kg i,p. 7 days after KET (BET30, 100)

 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

  • Ketamine 1 or 5 mg/kg i,p. acute (KET1, 5, respectively)

  • Guanosine (1 or 5 mg/kg i,p. acute (GUO1, 5, respectively)

  • Corticosterone 20 mg/kg p.o.—21 days (1 week after administration KET or GUO) (CORT)

  • Fluoxetine 10 mg/kg p.o. 3 weeks (FLU)

  • Corticosterone 20 mg/kg p.o. 3 weeks (after FLU) (CORT)

  • KET1 + GUO5—1 week before administration CORT—21 days (CORT)

 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

  • Chronic restraint stress (CRS)—21 days

  • CRS + Imipramine 20 mg/kg i.p. 21 days 30 min before stress (IMI)

 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

  • Chronic Unpredictable Mild Stress (CUMS)—8 weeks

  • CUMS + Fluoxetine 20 mg/kg were administered by oral gavage 4 weeks (4th-8th week of the experiment) (FLU)

  • CUMS + Asiaticoside 10, 20 or 40 mg/kg were administered by oral gavage 4 weeks (4th-8th week of the experiment) (ASI10, 20, 40, respectively)

 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

  • Lurasidone 3 mg/kg (LUR3)

  • Lurasidone 10 mg/kg (LUR10)

  • Fluoxetine 20 mg/kg (FLU20)

Drugs were administered orally for 2 weeks		 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

  • CRS—14 days

  • Fluoxetine 20 mg/kg i,p. 7 days after CRS (FLU)

 Basolateral
Amygdala		 Western Blot ↑PSD-95 protein after CRS
↓PSD-95 protein after CRS + FLU		 Yi et al. [136]
C57BL/6J male mice

  • CRS

  • CRS + (2R,6R)-Hydroxynorketamine 10 mg/kg i,p. on 15 day (HNK)

  • CRS+ HNK+ NBQX 10 mg/kg i,p. 30 min before HNK

  • CRS + HNK + ANA-12 0.5 mg/kg i,p. at the same time as HNK

 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

  • UCMS—8 weeks

  • UCMS +Alarin 1 nmol i.c.v. (Ala1)

  • UCMS + Alarin 2 nmol i.c.v. (Ala2)

  • UCMS + Ala2 + Rapamycin 3 mg/kg i,p. (Rapa)

 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

  • CRS—21 days

  • CRS + Imipramine 20 mg/kg i,p. 21 days 30 min before stress (IMI)

 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

  • Citalopram 10 mg/kg i,p. 5 days (CTM)

  • Sleep Deprivation 24h (SD)

  • CTM+SD

 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

  • Yueju-Ganmaidazao^ 1 g/kg i.g. 4 days (YG)

  • Escitalopram 10 mg/kg i.g. 4 days (ES)

  • Lipopolysaccharide 1 mg/kg i,p. 4 days (LPS)

  • LPS + YG 4 days

  • LPS + ES 4 days

  • Chronic Unpredictable Stress 3 weeks (CUS)+ YG

  • CUS + ES

 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

  • Chronic Learned Helplessness 13 days (training: 1–3, 8, 13 day) (cLH)

  • Yueju 1.25 g/kg in 0.9% saline for 21 days after cLH (YJ)

  • Fluoxetine 18 mg/kg in 0.9% saline for 21 days after cLH (FLU)

 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

  • Citalopram 10 mg/kg i,p. 5 days (CTM)

  • Sleep Deprivation 24h (SD)

  • CTM+SD

 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

  • Fear Conditioning (FC)—2 days + Ketamine 30 mg/kg i,p. (KET) acute 22 h after FC

 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

  • Chronic Unpredictable Mild Stress (CUMS; 8 weeks)

  • CUMS + High-frequency repetitive transcranial magnetic stimulation 15 Hz (15 Hz HF-rTMS; 4 weeks)

  • CUMS + High-frequency repetitive transcranial magnetic stimulation 25 Hz (25 Hz HF-rTMS; 4 weeks)

 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

  • Chronic behavioral despair model—5 days (CDM5)

  • CDM (for 4 weeks after CDM5 without any antidepressant treatment)

  • Imipramine 15 mg/kg in water for 4 weeks after CDM5 (IMI)

  • Fluoxetine 15 mg/kg for 4 weeks in water after CDM5 (FLU)

  • Ketamine 3 mg/kg i.p. (KET) after CDM5 Positive control; single injection in 32th day experiments

 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

  • Chronic Social Defeat Stress 10 days with CD-1 aggressor mouse (CSDS)

After 10 days of CSDS, the mice were separated into susceptible and resilient subpopulations based on behavioral tests		 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

  • Zn 40 mg/kg p.o. (Zn)

  • Imipramine 60 mg/kg p.o.(IMI)

  • Zn + IMI

Mice were decapitated sixty minutes following drug administration.		 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

  • Yueju-Ganmaidazao 1 g/kg by gavage 4 days (YG)

  • Escitalopram 10 mg/kg by gavage 4 days (ES)

  • Lipopolysaccharide 1 mg/kg i.p. 4 days (LPS)

  • LPS + YG 4 days

  • LPS + ES 4 days

  • Chronic Unpredictable Stress 3 weeks (CUS)+ YG

  • CUS + ES

 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]

Abbreviations: Asiaticoside —product derived from the plant Centella asiatica. It has been shown to possess wound healing, anti-inflammatory and liver protective effects. In addition, studies demonstrated that asiaticoside could attenuate neurobehavioral andneurochemical; Alarin—neuropeptide with antidepressant activity; Yueju-Ganmaidazao (YG)–an herbal medicine prescribed for the treatment of mood disorders, consisting of two classic traditional Chinese herbal medicines Yueju and Ganmaidazao. Yueju and Ganmaidazao are used to treat depression.