1,302
Views
20
CrossRef citations to date
0
Altmetric
Research Article

Genipin normalizes depression-like behavior induced by prenatal stress through inhibiting DNMT1

, , , &
Pages 310-317 | Received 06 Dec 2017, Accepted 05 Mar 2018, Published online: 03 May 2018

Figures & data

Figure 1. Depression-like behaviors in PRS mice are reversed by treatment with genipin. Forty-day-old NS (offspring of non-stressed dams) and PRS (offspring of prenatally stressed dams) male mice were treated i.p. once a day for 7 days, with vehicle (VEH), 25 mg/kg of genipin (GEP). The depression-like behaviors were measured 2 h after the last treatment by means of FST (A) and TST (B). Administration of genipin at the dose above normalizes locomotor (horizontal and vertical) hyperactivity in PRS but not NS mice (C and D). The data are expressed as mean +/- SEM of 10 mice per group. The indices for TST and FST are represented as seconds, while locomotor activities are expressed as counts during 15 min. # P < 0.05 when genipin (GEP)-treated PRS mice are compared to vehicle (VEH)-treated PRS mice *P < 0.05 when PRS mice are compared to vehicle (VEH)- and genipin (GEP)-treated NS mice.

Figure 1. Depression-like behaviors in PRS mice are reversed by treatment with genipin. Forty-day-old NS (offspring of non-stressed dams) and PRS (offspring of prenatally stressed dams) male mice were treated i.p. once a day for 7 days, with vehicle (VEH), 25 mg/kg of genipin (GEP). The depression-like behaviors were measured 2 h after the last treatment by means of FST (A) and TST (B). Administration of genipin at the dose above normalizes locomotor (horizontal and vertical) hyperactivity in PRS but not NS mice (C and D). The data are expressed as mean +/- SEM of 10 mice per group. The indices for TST and FST are represented as seconds, while locomotor activities are expressed as counts during 15 min. # P < 0.05 when genipin (GEP)-treated PRS mice are compared to vehicle (VEH)-treated PRS mice *P < 0.05 when PRS mice are compared to vehicle (VEH)- and genipin (GEP)-treated NS mice.

Figure 2. Downregulated expression of Bdnf-i, Bdnf-iv, Bdnf-vi, and Bdnf-ix transcripts in hippocampus of PRS mice are normalized by genipin. Forty-day-old NS (offspring of non-stressed dams) and PRS (offspring of prenatally stressed dams) male mice were treated i.p. once a day for 7 days, with vehicle (VEH), 25 mg/kg of genipin (GEP). Levels of mRNA were measured by qPCR and the data were normalized by β-actin. Bdnf expression was calculated by the ddCt method. Means of mRNA levels are expressed relative to control group. The data are expressed as mean +/- SEM. * P < 0.05 when vehicle (VEH)-treated PRS mice are compared to genipin (GEP)-treated PRS mice, or to vehicle (VEH)- and genipin (GEP)-treated NS mice. n = 10 per group.

Figure 2. Downregulated expression of Bdnf-i, Bdnf-iv, Bdnf-vi, and Bdnf-ix transcripts in hippocampus of PRS mice are normalized by genipin. Forty-day-old NS (offspring of non-stressed dams) and PRS (offspring of prenatally stressed dams) male mice were treated i.p. once a day for 7 days, with vehicle (VEH), 25 mg/kg of genipin (GEP). Levels of mRNA were measured by qPCR and the data were normalized by β-actin. Bdnf expression was calculated by the ddCt method. Means of mRNA levels are expressed relative to control group. The data are expressed as mean +/- SEM. * P < 0.05 when vehicle (VEH)-treated PRS mice are compared to genipin (GEP)-treated PRS mice, or to vehicle (VEH)- and genipin (GEP)-treated NS mice. n = 10 per group.

Figure 3. Reduced BDNF protein induced by prenatal stress is normalized by the treatment of genipin. Forty-day-old NS (offspring of non-stressed dams) and PRS (offspring of prenatally stressed dams) male mice were treated i.p. once a day for 7 days, with vehicle (VEH), 25 mg/kg of genipin (GEP). The immunoblots of BDNF protein in hippocampus were examined by Western blot and BDNF immunoblots were normalized by β-actin protein levels. The data are expressed as mean +/- SEM. * P < 0.05 when vehicle (VEH)-treated PRS mice are compared to genipin (GEP)-treated PRS mice, or to vehicle (VEH)- and genipin (GEP)-treated NS mice. n = 5 per group.

Figure 3. Reduced BDNF protein induced by prenatal stress is normalized by the treatment of genipin. Forty-day-old NS (offspring of non-stressed dams) and PRS (offspring of prenatally stressed dams) male mice were treated i.p. once a day for 7 days, with vehicle (VEH), 25 mg/kg of genipin (GEP). The immunoblots of BDNF protein in hippocampus were examined by Western blot and BDNF immunoblots were normalized by β-actin protein levels. The data are expressed as mean +/- SEM. * P < 0.05 when vehicle (VEH)-treated PRS mice are compared to genipin (GEP)-treated PRS mice, or to vehicle (VEH)- and genipin (GEP)-treated NS mice. n = 5 per group.

Figure 4. Enrichment of 5mC on Bdnf-i, Bdnf-iv, Bdnf-vi, and Bdnf-ix promoter regions in the hippocampus of PRS mice are reduced by treatment with genipin. Forty-day-old NS (offspring of non-stressed dams) and PRS (offspring of prenatally stressed dams) male mice were treated i.p. once a day for 7 days, with vehicle (VEH), 25 mg/kg genipin (GEP). The enrichment of 5mC was measured using MeDIP and the enrichments of 5mC were corrected by corresponding input DNA. The data are expressed as mean +/- SEM. * P < 0.05 when vehicle (VEH)-treated PRS samples are compared to genipin (GEP)-treated PRS samples or to vehicle (VEH)- and genipin (GEP)-treated NS mice. n = 10 per group.

Figure 4. Enrichment of 5mC on Bdnf-i, Bdnf-iv, Bdnf-vi, and Bdnf-ix promoter regions in the hippocampus of PRS mice are reduced by treatment with genipin. Forty-day-old NS (offspring of non-stressed dams) and PRS (offspring of prenatally stressed dams) male mice were treated i.p. once a day for 7 days, with vehicle (VEH), 25 mg/kg genipin (GEP). The enrichment of 5mC was measured using MeDIP and the enrichments of 5mC were corrected by corresponding input DNA. The data are expressed as mean +/- SEM. * P < 0.05 when vehicle (VEH)-treated PRS samples are compared to genipin (GEP)-treated PRS samples or to vehicle (VEH)- and genipin (GEP)-treated NS mice. n = 10 per group.

Figure 5. The increased expression of DNMT1 mRNA and protein in the hippocampus of PRS mice is reduced by treatment with genipin. Forty-day-old NS (offspring of non-stressed dams) and PRS (offspring of prenatally stressed dams) male mice were treated i.p. once a day for 7 days, with vehicle (VEH), 25 mg/kg of genipin (GEP). The Dnmt1 transcript was measured by qPCR and data were normalized by β-actin. PCR values were calculated by the Delta-Delta Ct (ddCt) method. Means of mRNA levels are expressed relative to control group (A). (B) DNMT1 protein was accessed by Western blot and the immunoblot of DNMT1 protein was normalized by β-actin protein levels. The data are expressed as mean +/- SEM. * P < 0.05 when vehicle (VEH)-treated PRS samples are compared to genipin (GEP)-treated PRS samples or to vehicle (VEH)- and genipin (GEP)-treated NS mice. n = 10 per group for qPCR and n = 5 per group for Western blot assay.

Figure 5. The increased expression of DNMT1 mRNA and protein in the hippocampus of PRS mice is reduced by treatment with genipin. Forty-day-old NS (offspring of non-stressed dams) and PRS (offspring of prenatally stressed dams) male mice were treated i.p. once a day for 7 days, with vehicle (VEH), 25 mg/kg of genipin (GEP). The Dnmt1 transcript was measured by qPCR and data were normalized by β-actin. PCR values were calculated by the Delta-Delta Ct (ddCt) method. Means of mRNA levels are expressed relative to control group (A). (B) DNMT1 protein was accessed by Western blot and the immunoblot of DNMT1 protein was normalized by β-actin protein levels. The data are expressed as mean +/- SEM. * P < 0.05 when vehicle (VEH)-treated PRS samples are compared to genipin (GEP)-treated PRS samples or to vehicle (VEH)- and genipin (GEP)-treated NS mice. n = 10 per group for qPCR and n = 5 per group for Western blot assay.
Supplemental material

Tab1_supplemental_information.doc

Download MS Word (37.5 KB)

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.