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Desvenlafaxine may accelerate neuronal maturation in the dentate gyri of adult male rats.

Asokan A, Ball AR, Laird CD, Hermer L, Ormerod BK - PLoS ONE (2014)

Bottom Line: To explore this link further, we tested whether the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine impacted adult hippocampal neurogenesis differently than its primary active SNRI metabolite desvenlafaxine.Our data expand the body of literature showing that antidepressants impact adult neurogenesis by stimulating NPC proliferation and perhaps the survival of neuronal progeny and by showing that a high dose of the SNRI antidepressant desvenlafaxine, but neither a high nor low venlafaxine dose, may also accelerate neuronal maturation in the adult rat hippocampus.These data support the hypothesis that hippocampal neurogenesis may indeed serve as a biomarker of depression and the effects of antidepressant treatment, and may be informative for developing novel fast-acting antidepressant strategies.

View Article: PubMed Central - PubMed

Affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering and Evelyn F. & William L. McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.

ABSTRACT
Adult hippocampal neurogenesis has been linked to the effects of anti-depressant drugs on behavior in rodent models of depression. To explore this link further, we tested whether the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine impacted adult hippocampal neurogenesis differently than its primary active SNRI metabolite desvenlafaxine. Adult male Long Evans rats (n = 5-6 per group) were fed vehicle, venlafaxine (0.5 or 5 mg) or desvenlafaxine (0.5 or 5 mg) twice daily for 16 days. Beginning the third day of drug treatment, the rats were given a daily bromodeoxyuridine (BrdU; 50 mg/kg) injection for 5 days to label dividing cells and then perfused 2 weeks after the first BrdU injection to confirm total new hippocampal cell numbers and their phenotypes. The high desvenlafaxine dose increased total new BrdU+ cell number and appeared to accelerate neuronal maturation because fewer BrdU+ cells expressed maturing neuronal phenotypes and more expressed mature neuronal phenotypes in the dentate gyri of these versus vehicle-treated rats. While net neurogenesis was not increased in the dentate gyri of rats treated with the high desvenlafaxine dose, significantly more mature neurons were detected. Our data expand the body of literature showing that antidepressants impact adult neurogenesis by stimulating NPC proliferation and perhaps the survival of neuronal progeny and by showing that a high dose of the SNRI antidepressant desvenlafaxine, but neither a high nor low venlafaxine dose, may also accelerate neuronal maturation in the adult rat hippocampus. These data support the hypothesis that hippocampal neurogenesis may indeed serve as a biomarker of depression and the effects of antidepressant treatment, and may be informative for developing novel fast-acting antidepressant strategies.

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Related in: MedlinePlus

High dose desvenlafaxine increases NPCproliferation and survival in the DG of rats.A)Representative brightfield image of BrdU+ cellsrevealed in the dentate gyrus of a vehicle-treated rat using DAB BrdU (inbrown). Scale bar  = 50 µm. B) Stereological estimates revealed more 10–14day-old BrdU+ cells in the dentate gyriof DES-HI- versus vehicle-treated rats (p = 0.01*).
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pone-0098530-g002: High dose desvenlafaxine increases NPCproliferation and survival in the DG of rats.A)Representative brightfield image of BrdU+ cellsrevealed in the dentate gyrus of a vehicle-treated rat using DAB BrdU (inbrown). Scale bar  = 50 µm. B) Stereological estimates revealed more 10–14day-old BrdU+ cells in the dentate gyriof DES-HI- versus vehicle-treated rats (p = 0.01*).

Mentions: Figure 2A shows a representative example of BrdU+ cells counted in the SGZs and GCLs of rats in each treatment group and Figure 2B shows the stereologically estimated mean (±S.E.M.) total number of BrdU+ cells found in these regions. Anti-depressant drug treatment significantly affected total BrdU+ cell number in the dentate gyri of adult male rats (F(4,21) = 3.16; p<0.05). Specifically, more new cells were found in the dentate gyri of rats treated with high dose of desvenlafaxine versus vehicle (p<0.05). Since 2 weeks elapsed between the first BrdU injection and perfusion, the effect of high desvenlafaxine on total new cell number could reflect stimulated NPC proliferation and/or enhanced new cell survival.


Desvenlafaxine may accelerate neuronal maturation in the dentate gyri of adult male rats.

Asokan A, Ball AR, Laird CD, Hermer L, Ormerod BK - PLoS ONE (2014)

High dose desvenlafaxine increases NPCproliferation and survival in the DG of rats.A)Representative brightfield image of BrdU+ cellsrevealed in the dentate gyrus of a vehicle-treated rat using DAB BrdU (inbrown). Scale bar  = 50 µm. B) Stereological estimates revealed more 10–14day-old BrdU+ cells in the dentate gyriof DES-HI- versus vehicle-treated rats (p = 0.01*).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4045676&req=5

pone-0098530-g002: High dose desvenlafaxine increases NPCproliferation and survival in the DG of rats.A)Representative brightfield image of BrdU+ cellsrevealed in the dentate gyrus of a vehicle-treated rat using DAB BrdU (inbrown). Scale bar  = 50 µm. B) Stereological estimates revealed more 10–14day-old BrdU+ cells in the dentate gyriof DES-HI- versus vehicle-treated rats (p = 0.01*).
Mentions: Figure 2A shows a representative example of BrdU+ cells counted in the SGZs and GCLs of rats in each treatment group and Figure 2B shows the stereologically estimated mean (±S.E.M.) total number of BrdU+ cells found in these regions. Anti-depressant drug treatment significantly affected total BrdU+ cell number in the dentate gyri of adult male rats (F(4,21) = 3.16; p<0.05). Specifically, more new cells were found in the dentate gyri of rats treated with high dose of desvenlafaxine versus vehicle (p<0.05). Since 2 weeks elapsed between the first BrdU injection and perfusion, the effect of high desvenlafaxine on total new cell number could reflect stimulated NPC proliferation and/or enhanced new cell survival.

Bottom Line: To explore this link further, we tested whether the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine impacted adult hippocampal neurogenesis differently than its primary active SNRI metabolite desvenlafaxine.Our data expand the body of literature showing that antidepressants impact adult neurogenesis by stimulating NPC proliferation and perhaps the survival of neuronal progeny and by showing that a high dose of the SNRI antidepressant desvenlafaxine, but neither a high nor low venlafaxine dose, may also accelerate neuronal maturation in the adult rat hippocampus.These data support the hypothesis that hippocampal neurogenesis may indeed serve as a biomarker of depression and the effects of antidepressant treatment, and may be informative for developing novel fast-acting antidepressant strategies.

View Article: PubMed Central - PubMed

Affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering and Evelyn F. & William L. McKnight Brain Institute, University of Florida, Gainesville, Florida, United States of America.

ABSTRACT
Adult hippocampal neurogenesis has been linked to the effects of anti-depressant drugs on behavior in rodent models of depression. To explore this link further, we tested whether the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine impacted adult hippocampal neurogenesis differently than its primary active SNRI metabolite desvenlafaxine. Adult male Long Evans rats (n = 5-6 per group) were fed vehicle, venlafaxine (0.5 or 5 mg) or desvenlafaxine (0.5 or 5 mg) twice daily for 16 days. Beginning the third day of drug treatment, the rats were given a daily bromodeoxyuridine (BrdU; 50 mg/kg) injection for 5 days to label dividing cells and then perfused 2 weeks after the first BrdU injection to confirm total new hippocampal cell numbers and their phenotypes. The high desvenlafaxine dose increased total new BrdU+ cell number and appeared to accelerate neuronal maturation because fewer BrdU+ cells expressed maturing neuronal phenotypes and more expressed mature neuronal phenotypes in the dentate gyri of these versus vehicle-treated rats. While net neurogenesis was not increased in the dentate gyri of rats treated with the high desvenlafaxine dose, significantly more mature neurons were detected. Our data expand the body of literature showing that antidepressants impact adult neurogenesis by stimulating NPC proliferation and perhaps the survival of neuronal progeny and by showing that a high dose of the SNRI antidepressant desvenlafaxine, but neither a high nor low venlafaxine dose, may also accelerate neuronal maturation in the adult rat hippocampus. These data support the hypothesis that hippocampal neurogenesis may indeed serve as a biomarker of depression and the effects of antidepressant treatment, and may be informative for developing novel fast-acting antidepressant strategies.

Show MeSH
Related in: MedlinePlus