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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 do not show more anxiety in the sucrose preference test. Mice were habituated to freely accessible plain drinking water and 1% sucrose water for 3 d. Then, after 16 h of water deprivation, they were given access to both plain and sucrose water for 24 h. The consumption from each bottle was measured after the first 20 min of the test and again at the end of the test. A, Percentage of sucrose water consumption at 20 min. B, Percentage of sucrose water consumption at the end of the 24 h test. C, Total consumption from the two bottles in 24 h. n.s., Not significant.
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Figure 10: ERK5 icKO mice do not show more anxiety in the sucrose preference test. Mice were habituated to freely accessible plain drinking water and 1% sucrose water for 3 d. Then, after 16 h of water deprivation, they were given access to both plain and sucrose water for 24 h. The consumption from each bottle was measured after the first 20 min of the test and again at the end of the test. A, Percentage of sucrose water consumption at 20 min. B, Percentage of sucrose water consumption at the end of the 24 h test. C, Total consumption from the two bottles in 24 h. n.s., Not significant.

Mentions: Next, we evaluated whether ERK5 deletion affects the animal’s interest in pleasure using the sucrose-preference assay. Mice were given access to both sucrose water and plain water. A significant preference to sucrose water versus plain water indicates the interest for pleasure. We first habituated both the ERK5 icKO mice and control mice to freely available water and 1% sucrose for 3 d. After 16 h of fluid deprivation, mice were reintroduced to both bottles and their preference for each bottle was measured during a 20 min test followed by a 24 h test. Both groups preferred the sucrose drink over the plain water in the first 20 min (p = 0.799, ERK5 icKO mice vs control mice)20 (Fig. 10A) as well as over the next 24 h (p = 0.188, ERK5 icKO mice vs control mice)21 (Fig. 10B), and they consumed the same amount of total liquid (p = 0.468)22 (Fig. 10C).


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 do not show more anxiety in the sucrose preference test. Mice were habituated to freely accessible plain drinking water and 1% sucrose water for 3 d. Then, after 16 h of water deprivation, they were given access to both plain and sucrose water for 24 h. The consumption from each bottle was measured after the first 20 min of the test and again at the end of the test. A, Percentage of sucrose water consumption at 20 min. B, Percentage of sucrose water consumption at the end of the 24 h test. C, Total consumption from the two bottles in 24 h. n.s., Not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 10: ERK5 icKO mice do not show more anxiety in the sucrose preference test. Mice were habituated to freely accessible plain drinking water and 1% sucrose water for 3 d. Then, after 16 h of water deprivation, they were given access to both plain and sucrose water for 24 h. The consumption from each bottle was measured after the first 20 min of the test and again at the end of the test. A, Percentage of sucrose water consumption at 20 min. B, Percentage of sucrose water consumption at the end of the 24 h test. C, Total consumption from the two bottles in 24 h. n.s., Not significant.
Mentions: Next, we evaluated whether ERK5 deletion affects the animal’s interest in pleasure using the sucrose-preference assay. Mice were given access to both sucrose water and plain water. A significant preference to sucrose water versus plain water indicates the interest for pleasure. We first habituated both the ERK5 icKO mice and control mice to freely available water and 1% sucrose for 3 d. After 16 h of fluid deprivation, mice were reintroduced to both bottles and their preference for each bottle was measured during a 20 min test followed by a 24 h test. Both groups preferred the sucrose drink over the plain water in the first 20 min (p = 0.799, ERK5 icKO mice vs control mice)20 (Fig. 10A) as well as over the next 24 h (p = 0.188, ERK5 icKO mice vs control mice)21 (Fig. 10B), and they consumed the same amount of total liquid (p = 0.468)22 (Fig. 10C).

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