Dexmedetomidine improving complete Freund’s adjuvant-induced anxiety-like and depression-like behaviour by promoting the expression of brain-derived&nbsp; neurotrophic factor-tyrosin kinase receptor B in mice hippocampus

WANG Ya-Juan; YANG Bin; ZENG Xue-Qing; LIANG Yue; LIU Zhi-Wen; CAO Wen-Yu; ZHONG Xiao-Lin

doi:10.16098/j.issn.0529-1356.2023.02.008

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Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (2) : 181-187. DOI: 10.16098/j.issn.0529-1356.2023.02.008

Dexmedetomidine improving complete Freund’s adjuvant-induced anxiety-like and depression-like behaviour by promoting the expression of brain-derived neurotrophic factor-tyrosin kinase receptor B in mice hippocampus

WANG Ya-juan¹ YANG Bin² ZENG Xue-qing³ LIANG Yue¹ LIU Zhi-wen² CAO Wen-yu^3* ZHONG Xiao-lin^1*

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Abstract

Objective To study the effect of dexmedetomidine (DEX), an α2- adrenoceptor agonist, on the pain-related anxiety-like and depression-like behaviour induced by complete Freund’s adjuvant (CFA) injection and its possible regulatory mechanism. Methods Thirty-six ICR female mice were randomly divided into normal saline (NS) group, CFA group and DEX+CFA group, n=12 for each group. Chronic inflammatory pain model was established by subcutaneous injection of 10 μl CFA into the right hind limb of mice. DEX+CFA group mice were injected intraperitoneally with 0.025 mg/kg DEX 30 minutes before nociceptive behavior test, and once a day for 7 days. Von-frey fiber was used to evaluate the threshold of mechanical pain in mice, n=12 for each group. The anxiety-like behavior of mice were detected by open field test, n=12 for each group. Sucrose preference, tail suspension test and forced swimming test were used to detected the depression-like behavior of mice, n=12 for each group. The expression of adrenergic receptor β2 (ADRB2), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB), and glutamate receptors 1(GluR1) and GluR2 were detected by Western blotting, n=8 for each group. Immunohistochemical staining was used to detect the expression of recombinant doublecortin(DCX), which is a marker of newborn neurons in the hippocampus, n=4 for each group. Results Compared with the NS group, the mechanical threshold of mice on the 1st, 3rd and 7th day after CFA injection decreased significantly (P<0.05); But there was no significant difference between DEX+CFA group and CFA group (P>0.05). Compared with the NS group, the time spent in the inner ares (P<0.01), number of entering the central grid area (P<0.01) and distance travelled in the inner area (P<0.01) of CFA group mice reduced significantly, while the time (P<0.01), numbers (P<0.05) and distance（P<0.05）of DEX+CFA group mice entering the central grid area enhanced significantly. The result of depression-like behavior tests showed that the sucrose preference percentage (P<0.05) reduced significantly in CFA group when compared with NS group, and the immobility time increased significantly in tail suspension test (P<0.01) and forced swimming test (P<0.001) in CFA mice when compared with NS group, while DEX intervention could significantly increase the sucrose preference scores (P<0.05) and decreased the immobility time in tail suspension test (P<0.05) and forced swimming test (P<0.05). The result of Western blotting showed that compared with the NS group, the levels of ADRB2 (P<0.0010), BDNF (P<0.001), TrkB (P<0.01), GluR1 (P<0.001) and GluR2 (P<0.001) in the hippocampus of CFA group were significantly decreased, while DEX intervention could significantly increase the expression of ADRB2 (P<0.05), BDNF (P<0.001), TrkB (P<0.001), GluR1 (P<0.001) and GluR2 (P<0.001). Immunohistochemical result showed that compared with the NS group, the average absorbance(AA) of DCX decreased significantly in hippocampus of CFA group (P<0.05), but increased significantly in DEX+CFA group (P<0.05). Conclusion Dexmedetomidine may promote hippocampal neurogenesis through upregulated the expression of BDNF-TrkB, thus improving CFA-induced anxiety-like and depression-like behaviors in mice.

Key words

Chronic pain

/ Dexmedetomidine / Brain-derived neurotrophic factor / Neurogenesis / Anxietylikebehavior / Depressionlikebehavior / Westernblotting / Mouse

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WANG Ya-juan YANG Bin ZENG Xue-qing LIANG Yue LIU Zhi-wen CAO Wen-yu ZHONG Xiao-lin.

[J]. Acta Anatomica Sinica. 2023, 54(2): 181-187 https://doi.org/10.16098/j.issn.0529-1356.2023.02.008

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