Review Article

Dendritic Spines in Depression: What We Learned from Animal Models

Table 1

The effects of chronic stress on dendritic spines in hippocampus.

#StressParadigmsAnimals CA1CA3References

1CRS6 h/day for 21 daysMale SD ratsndApical, not basal dendritic atrophy[28]

2CRS6 h/day for 21 daysMale SD ratsnd↑ spine density in apical, basal dendrites[29]

3CRS or multiple stress (CMS): 3 different stressors CRS, 6 h/day for 21 days
CMS: 3 stressors/day for 21 days
Male SD rats ndApical dendritic atrophy; CORT habituates to 21-day CRS but not 21-day CMS[30]

4CRS6 h/day for 21 daysMale SD ratsndApical dendritic atrophy is blocked by cyanoketone or CGP43487[31]

5CRS6 h/day for 21 days Male SD ratsnd↑ synaptic vesicle density in MFT[32]

6CRS6 h/day for 21 daysMale SD ratsndApical dendritic atrophy, recovery after 10 days
↓ spine density
[33]

7CRS6 h/day for 21 daysAdult male Wister ratsnd↑ excitatory MF-CA3 synapses, recovery after maze learning [34]

8Acute restraint plus intermittent tail shock30 shocks: 1 mA, 1 s, 1/minAdult male and female SD rats↑ spine density in male and ↓ in female apical dendrites, both 100% blocked by CPPnd[35]

9CRS6 h/day for 21 daysMale Wistar ratsnd↓ PSD number; ↓ spine density in apical dendrites
Retraction of dendritic TE with ↓ in their volume
[36]

10CRS6 h/day for 21 daysAdult SD adult female rats dendritic atrophy
↑ spine density
↑ spine size
Apical dendritic atrophy
Spine density, nd
[37, 38]

11CRS6 h/day for 21 daysMale Wistar rats↑ PSD surface and ↑ PSD volume; excitatory synapses in stratum nd[39]

12CRS6 h/day for 21 daysC57/BL6 male Wt mice↓ spine density in apical dendrite
↓ NR1, NR2B, NR2A, and GAP43
These decreases are tPA and plasminogen dependent[40]

13CRS6 h/day for 21 daysC57/BL6 male Wt mice dendritic atrophy; ↓ total spine density, stubby spines
↓ thin and mushroom spine density
Apical, not basal dendritic atrophy
total spine density, ↑ stubby spines, ↓ thin and mushroom spines
[41]

14CRS6 h/day for 21 daysAdult SD female rats dendritic atrophy
↑ spine density
↑ mushroom spine
Apical dendritic atrophy
↓ spine density
[42]

15CRS2.5 h/day for 14 daysMale rats↓ spine density in apical dendritesnd[43]

16CRS6 h/day for 21 daysAdult SD male rats↑ spine densityApical dendritic atrophy, ↓ spine density, and ↑ spinophilin and Homer1[44]

17CRS6 h/day for 21 daysFemale mice↓ spine density in apical dendritesnd[45]

18CRS2.5 h/day for 14 daysAdult male SD rats↓ spine density, ↓ cadherin, and LIMK/cofilin and p-LIMK/p-cofilinnd[46]

19CRS6 h/day for 25 daysFemale, male Long-Evans rats↓ spine density in basilar dendrites; ↑ apical dendritic arbors in female, not male ventral CA1Deficits in spatial memory in female but not male [47]

20CRS6 h/day for 21 daysAdult male mice↓ spine density; ↓ p-Akt, ↓ p-GSK-3β, and ↓ p-Erk1/2nd[48]

21CUMS1 stressor/day for 30 daysMale Wister rats apical dendrite Apical dendritic atrophy; ↓ MF-CA3 synapses[49]

22CUMS2 stressors/day for 10 daysMale Wister ratsnd CA3 dendrites[50]

23CUMS1 stressor/day for 21 daysMale SD rats↓ CA1 spine density↓ CA3 spine density, ↓ Kalirin-7 protein in hippocampus[24]

24CUMS1 stressor/day for 14 daysMale micend↑ CA3 spine density[51]

25CUMS1 stressor/day for 8 weeksMale SD rat↓ PSD thickness in CA1
↓ PSD95 protein
↓ PSD93, ↓ PSD95, ↓ SYN, ↓ spinophilin, and ↓ synapsin 1[52]

26CUMS2-3 stressors/day for 21–35 daysAdult SD ratsImpaired AMPAR-synaptic excitation at TA-CA1 synapses
↓ GluR1 and PSD95
Induces depression-like behaviors[53]

27CUMS2 stressors/day for 28 daysMale C57/b mice↓ mGlu2 receptors in susceptible, not resilient micemGLu2 deletion in mice results in a more severe susceptibility to stress[54]

28Multimodal stressAdult male C57BL/6J mice5 h↓ synapse numbers in dorsal apical dendrites
↓ PSD-95-ir puncta
↓ synapse numbers in dorsal CA3 apical
↓ PSD-95-ir puncta
[55]

29Psychosocial stress1 h/day for 28 daysMale tree shrewsndApical, not basal dendritic atrophy
spine density
[56]

30Psychosocial stress1 h/day for 28 daysMale ratsndApical dendritic atrophy[57]

31Chronic CORT exposure3-4 weeksMale SD ratsImpaired AMPAR-synaptic excitation at TA-CA1 synapses
↓ GluR1 protein
Induces depression-like behaviors[58]

32CORT exposure35 daysC57/BL6 male mice↓ CA1 thin and stubby spine density, but not mushroom spines CA3 spine density[59]

CRS: chronic restraint stress. CUMS: chronic unpredictable mild stress. TA: temporoammonic. CORT: corticosterone. MFT: mossy fiber terminals. TE: thorny excrescences in the stratum lucidum of CA3. : no change. ↓: decrease. ↑: increase. nd: not done.