Limits...
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 are not deficient in an open-field test. Naïve mice were introduced into an open-field arena for 20 min. Activity was scored by the TruScan software. A, There was no difference in the total number of moves, the total distance traveled, or the total time spent moving in the floor plane between ERK5 icKO mice and control mice. B, The ERK5 icKO mice did not exhibit reduced exploration in the center of the arena, shown as the number of entries to the center, the distance traveled, or the time spent in the center of the arena. n.s., Not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4596085&req=5

Figure 4: ERK5 icKO mice are not deficient in an open-field test. Naïve mice were introduced into an open-field arena for 20 min. Activity was scored by the TruScan software. A, There was no difference in the total number of moves, the total distance traveled, or the total time spent moving in the floor plane between ERK5 icKO mice and control mice. B, The ERK5 icKO mice did not exhibit reduced exploration in the center of the arena, shown as the number of entries to the center, the distance traveled, or the time spent in the center of the arena. n.s., Not significant.

Mentions: Conditional deletion of erk5 impairs multiple forms of hippocampus-dependent learning and memory, including contextual fear memory, spatial learning and memory, and pattern separation (Pan et al., 2012c; Pan et al., 2012a, 2013). To evaluate the level of anxiety of ERK5 icKO mice, we first subjected the mice to a series of behavior assays, including the open-field, elevated-plus maze, and the dark/light exploration tests, to test the animal’s adaptation and spontaneous exploration in new environments. In the open-field assay, a mouse was placed in an unfamiliar arena and locomotor activity was recorded. The level of anxiety is primarily assessed by the level of ambulation and the avoidance of exploration to the center of the arena (Bourin et al., 2007; Ramos, 2008). In comparison to control littermates, ERK5 icKO mice did not change the overall ambulation level, quantified as the number of moves (p = 0.324; Table 1)1, moving distance (p = 0.460)2, and moving time (p = 0.419)3 on the floor plane (Fig. 4A), nor did they show reduced exploration to the center of the arena, expressed as the number of entries to the center (p = 0.760)4, and the time spent in the center of the arena (p = 0.512)5 (Fig. 4B). These data indicate that non-stressed ERK5 icKO mice do not display overt anxiety-like behavior in the open-field assay.


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 are not deficient in an open-field test. Naïve mice were introduced into an open-field arena for 20 min. Activity was scored by the TruScan software. A, There was no difference in the total number of moves, the total distance traveled, or the total time spent moving in the floor plane between ERK5 icKO mice and control mice. B, The ERK5 icKO mice did not exhibit reduced exploration in the center of the arena, shown as the number of entries to the center, the distance traveled, or the time spent in the center of the arena. n.s., Not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: ERK5 icKO mice are not deficient in an open-field test. Naïve mice were introduced into an open-field arena for 20 min. Activity was scored by the TruScan software. A, There was no difference in the total number of moves, the total distance traveled, or the total time spent moving in the floor plane between ERK5 icKO mice and control mice. B, The ERK5 icKO mice did not exhibit reduced exploration in the center of the arena, shown as the number of entries to the center, the distance traveled, or the time spent in the center of the arena. n.s., Not significant.
Mentions: Conditional deletion of erk5 impairs multiple forms of hippocampus-dependent learning and memory, including contextual fear memory, spatial learning and memory, and pattern separation (Pan et al., 2012c; Pan et al., 2012a, 2013). To evaluate the level of anxiety of ERK5 icKO mice, we first subjected the mice to a series of behavior assays, including the open-field, elevated-plus maze, and the dark/light exploration tests, to test the animal’s adaptation and spontaneous exploration in new environments. In the open-field assay, a mouse was placed in an unfamiliar arena and locomotor activity was recorded. The level of anxiety is primarily assessed by the level of ambulation and the avoidance of exploration to the center of the arena (Bourin et al., 2007; Ramos, 2008). In comparison to control littermates, ERK5 icKO mice did not change the overall ambulation level, quantified as the number of moves (p = 0.324; Table 1)1, moving distance (p = 0.460)2, and moving time (p = 0.419)3 on the floor plane (Fig. 4A), nor did they show reduced exploration to the center of the arena, expressed as the number of entries to the center (p = 0.760)4, and the time spent in the center of the arena (p = 0.512)5 (Fig. 4B). These data indicate that non-stressed ERK5 icKO mice do not display overt anxiety-like behavior in the open-field assay.

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