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

From: MIF: Mood Improving/Inhibiting Factor?

Authors Model (n) Intervention Analysis Results
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
  1. ECS = electroconvulsive shock; FST = forced swim test; icv = intracerebroventricular injection; ip = intraperitoneal injection; IR = immunoreactive; KO = knockout; od = once daily; WT = wild-type.