Depression is a mental health problem
with typically high levels
of distress and dysfunction, and 150 mg/L fluoride (F) can induce
depression-like behavior. The development of depression is correlated
with neuronal atrophy, insufficient secretion of monoamine neurotransmitters,
extreme deviations from the normal microglial activation status, and
immune-inflammatory response. Studies found that Se supplementation
was related to the improvement of depression. In this study, we applied
selenium nanoparticles (SeNPs) for F-induced depression disease mitigation
by regulating the histopathology, metabolic index, genes, and protein
expression related to the JAK2-STAT3 signaling pathway in vivo. Results
showed that F and 2 mg Se/kg BW/day SeNPs lowered the dopamine (DA)
content (P < 0.05), altered the microglial morphology,
ramification index as well as solidity, and triggered the microglial
neuroinflammatory response by increasing the p-STAT3 nuclear translocation
(P < 0.01). Furthermore, F reduced the cortical
Se content and the number of surviving neurons (P < 0.05), increasing the protein expressions of p-JAK2/JAK2 and
p-STAT3/STAT3 of the cortex (P < 0.01), accompanied
by the depression-like behavior. Importantly, 1 mg Se/kg BW/day SeNPs
alleviated the microglial ramification index as well as solidity changes
and decreased the interleukin-1β secretion induced by F by suppressing
the p-STAT3 nuclear translocation (P < 0.01).
Likewise, 1 mg Se/kg BW/day SeNPs restored the F-disturbed dopamine
and noradrenaline secretion, increased the number of cortical surviving
neurons, and reduced the vacuolation area, ultimately suppressing
the occurrence of depression-like behavior through inhibiting the
JAK2-STAT3 pathway activation. In conclusion, 1 mg Se/kg BW/day SeNPs
have mitigation effects on the F-induced depression-like behavior.
The mechanism of how SeNPs repair neural functions will benefit depression
mitigation. This study also indicates that inhibiting the JAK/STAT
pathway can be a promising novel treatment for depressive disorders.