Table 1 Animal studies of macrophage migration inhibitory factor (MIF) in the setting of depression or depressive etiologies

Conboy et al. [36]

Adult male Wistar rats (48)

Chronic unpredictable stress, chronic corticosterone

Immunohistochemistry for Ki-67, MIF-IR cells in dentate gyrus

MIF co-localizes with proliferative markers

MIF levels correlate with neurogenesis

WT and MIF KO mice (16)

Fluoxetine (ip, od/14days), ISO1 (od/14days)

Immunohistochemistry for PCNA, DCX, BrdU, Ki-67, MIF-IR cells in dentate gyrus

Loss of MIF results in decreased basal and antidepressant-stimulated neurogenesis

WT and MIF KO mice (9, 16, 20, 8)

Acute stress exposure

ELISA for serum corticosterone, Western blot for receptor expression

MIF KO mice show no significant difference from WT in levels of serum glucocorticoids or receptor expression

WT and MIF KO mice (52, 20)

None

FST, water maze, acoustic fear conditioning

MIF KO mice show increased behavioral despair

MIF KO mice show impaired hippocampal spatial learning and memory, intact amygdalar fear conditioning

Moon et al. [69]

Male Sprague–Dawley rats (13, 4)

Voluntary exercise (running wheel), ECS (55 mA pulses, 100/s)

RT-PCR, Western blot, immunohistochemistry for MIF mRNA/protein

MIF mRNA is upregulated by exercise and ECS

Neuro-2A and RBL-2H3 cells (3); WT and MIF KO mice (12 to 16); male Sprague–Dawley rats (8 to 12)

MIF (300 ng/mL), exercise/ECS (see above), MIF (icv), CD74 siRNA, CT04 (5ug/mL), U0126 (10 uM)

RT-PCR for candidate genes (Bdnf, Fgf2) and neurogenesis genes (Dcx, Pax6), HPLC for 5HT, Western blot for P-ERK1/2

MIF induces expression of BDNF and Tph2, and also increases intracellular concentrations of 5HT

Effects on BDNF, Tph2, and 5HT are CD74 and ERK1/2 dependent

WT and MIF KO mice (12 to 16); male Sprague–Dawley rats (16 to 20)

Exercise (see above), MIF (icv)

FST

MIF KO mice show diminished antidepressant effects of exercise

Exogenous recombinant MIF has antidepressant activity