Objective To investigate the effects of minocycline, a neuroinflammation inhibitor, on the
depressive behaviors and neurotransmitters in the vascular depression mice model.
Methods Male CD1 mice were subject to repeated common carotid artery occlusion and
reperfusion to establish the vascular depression model, then randomly divided into experimental
group (n =10), control group (n =10) and sham group (n =10). Minocycline (30 mg/kg, i.p.) and same
dose of saline were administrated immediately after the surgery and subsequently the consecutive
6 days in experimental group and control group respectively. Mice in sham group were conducted
the same surgery expect occluding carotid artery, then administered the same dose of saline as the
control group. After the administration, tail suspension test and open-field test were used to assess
depression behaviors of mice on the post operation day (POD) 8 and 9 respectively, and Morris
water maze was used to assess cognitive function on the POD 10. On POD 11, mice were deeply
anesthetized and euthanized and transcardially perfused with phosphate buffered saline (PBS).
Expressions of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6)
in hippocampus were measured by enzyme-linked immunosorbent assay (ELISA) kit. Contents
of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) were measured by high
performance liquid chromatography (HPLC).
Results Among the three groups, the immobility time was significantly different ([174.75±11.37]s
vs [194.32±14.32]s vs [169.62±19.27]s, F =6.59, P =0.005), and the immobility time of experimental
group and sham group was shorter than control group significantly. The times of exploring holes,
prolonged time and distance of movement were significantly different (F =6.17, P =0.008; F =11.55,
P <0.001; F =13.47, P <0.001), the times of exploring holes of experimental group and sham group
was more than control group significantly, and so did both prolonged time and distance of movement
of those two groups. But there was significant difference in escape latency ([87.38±13.36]s vs
[88.50±19.88]s vs [44.38±19.76]s, F =16.09, P <0.001) among the three groups, the escape latency
of experimental group and control group was significantly longer than sham group. The expression
of TNF-α, IL-1β and IL-6 in hippocampus were down-regulated in experimental group and sham
group compared with control group (TNF-α:[141.10±24.36]pg/100 mg vs [167.6±15.91]pg/100 mg
vs [123.8±15.53]pg/100 mg, F =13.42, P <0.001; IL-6:[20.01±3.62]pg/mg vs [24.39±5.04]pg/mg vs
[18.40±3.78]pg/mg, F =5.49, P =0.010; IL-1β ([5.32±1.89]pg/mg vs [10.31±2.83]pg/mg vs [4.50±2.07]
pg/mg, F =18.69, P <0.001). There were no significant difference in the level of NE among the three
groups ([3.97±1.35]ng/ml vs [3.16±1.55]ng/ml vs [4.68±1.99]ng/ml, F =2.13, P =0.139), but there
is a increased level of DA in experimental group and sham group compared with control group
([10.72±2.65] ng/ml, [11.76±3.10] ng/ml vs [7.99±2.31] ng/ml).
Conclusion Minocycline can restrain the expression of inflammatory cytokines in vascular
depression mice, and inhibited inflammation may improve their depression behaviors, but no
improvement found in the cognitive impairment. Among those relevant neurotransmitters, the
content of DA changes most significantly.
