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Conditional Inhibition of Adult Neurogenesis by Inducible and Targeted Deletion of ERK5 MAP Kinase Is Not Associated with Anxiety/Depression-Like Behaviors(1,2).

Zou J, Wang W, Pan YW, Abel GM, Storm DR, Xia Z - eNeuro (2015)

Bottom Line: Although there is evidence that adult neurogenesis contributes to the therapeutic efficacy of chronic antidepressant treatment for anxiety and depression disorders, the role of adult neurogenesis in the onset of depression-related symptoms is still open to question.To address this issue, we utilized a transgenic mouse strain in which adult neurogenesis was specifically and conditionally impaired by Nestin-CreER-driven, inducible knockout (icKO) of erk5 MAP kinase in Nestin-expressing neural progenitors of the adult mouse brain upon tamoxifen administration.Our findings indicate that impaired adult neurogenesis does not lead to anxiety or depression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Toxicology Program in the Department of Environmental and Occupational Health Sciences.

ABSTRACT
Although there is evidence that adult neurogenesis contributes to the therapeutic efficacy of chronic antidepressant treatment for anxiety and depression disorders, the role of adult neurogenesis in the onset of depression-related symptoms is still open to question. To address this issue, we utilized a transgenic mouse strain in which adult neurogenesis was specifically and conditionally impaired by Nestin-CreER-driven, inducible knockout (icKO) of erk5 MAP kinase in Nestin-expressing neural progenitors of the adult mouse brain upon tamoxifen administration. Here, we report that inhibition of adult neurogenesis by this mechanism is not associated with an increase of the baseline anxiety or depression in non-stressed animals, nor does it increase the animal's susceptibility to depression after chronic unpredictable stress treatment. Our findings indicate that impaired adult neurogenesis does not lead to anxiety or depression.

No MeSH data available.


Related in: MedlinePlus

ERK5 icKO mice performed similarly to the controls in the elevated-plus maze. Mice were placed in the elevated-plus maze and allowed to explore for 5 min. Exploratory activity and immobility were analyzed by AnyMaze Software. A, Time spent in open arms and closed arms. B, Time spent in open and closed ends (the distal one-third of the open and closed arms). C, Time spent immobile in the open and closed arms. D, Total time immobile in the entire maze. n.s., Not significant.
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Figure 5: ERK5 icKO mice performed similarly to the controls in the elevated-plus maze. Mice were placed in the elevated-plus maze and allowed to explore for 5 min. Exploratory activity and immobility were analyzed by AnyMaze Software. A, Time spent in open arms and closed arms. B, Time spent in open and closed ends (the distal one-third of the open and closed arms). C, Time spent immobile in the open and closed arms. D, Total time immobile in the entire maze. n.s., Not significant.

Mentions: To confirm the findings from the open-field assay, we subjected the ERK5 icKO and control mice to two approach−avoidance conflict-based behavioral paradigms for assessing anxiety behaviors: the elevated-plus maze and the light/dark exploration test. The elevated-plus maze is based on the natural aversion of rodents for open spaces; decreased exploration in the open arms is a sign of anxiety (Bourin et al., 2007; Ramos, 2008). The ERK5 icKO mice did not exhibit an increased avoidance to the open spaces compared to control mice, quantified by the amount of time spent in the open arms (p = 0.630)6 and the open ends defined as the distal one-third of open arms (p =0.758)7 (Fig. 5A,B). However, it is still possible that ERK5 icKO mice spent more time in immobility while they were in the open arms, a hidden sign of elevated maladaption. We therefore analyzed the immobile behavior in the open arms and found that ERK5 icKO mice did not exhibit an increase of immobility in the open arms (p = 0.725)8 (Fig. 5C), confirming that they were actively exploring the open arms as control mice did. Their overall fear response to a novel environment was not compromised by ERK5 deletion, as both groups of mice spent about 50% of time (150 s during the 5 min test) in immobility on the apparatus (p = 0.543)9 (Fig. 5D). These results indicate that ERK5 icKO mice are not deficient in their ability to explore an unfamiliar and open environment, and they do not exhibit increased anxiety in the elevated-plus maze test.


Conditional Inhibition of Adult Neurogenesis by Inducible and Targeted Deletion of ERK5 MAP Kinase Is Not Associated with Anxiety/Depression-Like Behaviors(1,2).

Zou J, Wang W, Pan YW, Abel GM, Storm DR, Xia Z - eNeuro (2015)

ERK5 icKO mice performed similarly to the controls in the elevated-plus maze. Mice were placed in the elevated-plus maze and allowed to explore for 5 min. Exploratory activity and immobility were analyzed by AnyMaze Software. A, Time spent in open arms and closed arms. B, Time spent in open and closed ends (the distal one-third of the open and closed arms). C, Time spent immobile in the open and closed arms. D, Total time immobile in the entire maze. n.s., Not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596085&req=5

Figure 5: ERK5 icKO mice performed similarly to the controls in the elevated-plus maze. Mice were placed in the elevated-plus maze and allowed to explore for 5 min. Exploratory activity and immobility were analyzed by AnyMaze Software. A, Time spent in open arms and closed arms. B, Time spent in open and closed ends (the distal one-third of the open and closed arms). C, Time spent immobile in the open and closed arms. D, Total time immobile in the entire maze. n.s., Not significant.
Mentions: To confirm the findings from the open-field assay, we subjected the ERK5 icKO and control mice to two approach−avoidance conflict-based behavioral paradigms for assessing anxiety behaviors: the elevated-plus maze and the light/dark exploration test. The elevated-plus maze is based on the natural aversion of rodents for open spaces; decreased exploration in the open arms is a sign of anxiety (Bourin et al., 2007; Ramos, 2008). The ERK5 icKO mice did not exhibit an increased avoidance to the open spaces compared to control mice, quantified by the amount of time spent in the open arms (p = 0.630)6 and the open ends defined as the distal one-third of open arms (p =0.758)7 (Fig. 5A,B). However, it is still possible that ERK5 icKO mice spent more time in immobility while they were in the open arms, a hidden sign of elevated maladaption. We therefore analyzed the immobile behavior in the open arms and found that ERK5 icKO mice did not exhibit an increase of immobility in the open arms (p = 0.725)8 (Fig. 5C), confirming that they were actively exploring the open arms as control mice did. Their overall fear response to a novel environment was not compromised by ERK5 deletion, as both groups of mice spent about 50% of time (150 s during the 5 min test) in immobility on the apparatus (p = 0.543)9 (Fig. 5D). These results indicate that ERK5 icKO mice are not deficient in their ability to explore an unfamiliar and open environment, and they do not exhibit increased anxiety in the elevated-plus maze test.

Bottom Line: Although there is evidence that adult neurogenesis contributes to the therapeutic efficacy of chronic antidepressant treatment for anxiety and depression disorders, the role of adult neurogenesis in the onset of depression-related symptoms is still open to question.To address this issue, we utilized a transgenic mouse strain in which adult neurogenesis was specifically and conditionally impaired by Nestin-CreER-driven, inducible knockout (icKO) of erk5 MAP kinase in Nestin-expressing neural progenitors of the adult mouse brain upon tamoxifen administration.Our findings indicate that impaired adult neurogenesis does not lead to anxiety or depression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Toxicology Program in the Department of Environmental and Occupational Health Sciences.

ABSTRACT
Although there is evidence that adult neurogenesis contributes to the therapeutic efficacy of chronic antidepressant treatment for anxiety and depression disorders, the role of adult neurogenesis in the onset of depression-related symptoms is still open to question. To address this issue, we utilized a transgenic mouse strain in which adult neurogenesis was specifically and conditionally impaired by Nestin-CreER-driven, inducible knockout (icKO) of erk5 MAP kinase in Nestin-expressing neural progenitors of the adult mouse brain upon tamoxifen administration. Here, we report that inhibition of adult neurogenesis by this mechanism is not associated with an increase of the baseline anxiety or depression in non-stressed animals, nor does it increase the animal's susceptibility to depression after chronic unpredictable stress treatment. Our findings indicate that impaired adult neurogenesis does not lead to anxiety or depression.

No MeSH data available.


Related in: MedlinePlus