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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

The same cohort of ERK5 icKO mice that show impaired hippocampus-dependent memory do not exhibit anxiety/depression-like behavior. A, ERK5 icKO mice are impaired in remote memory when the erk5 gene was inducibly deleted. Data are from Figure 2 of Pan et al. (2012a). **p < 0.01. B, C, These mice are not deficient in a dark/light exploration test (B) or tail-suspension test (C), performed sequentially after the remote memory test. n.s., Not significant.
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Figure 14: The same cohort of ERK5 icKO mice that show impaired hippocampus-dependent memory do not exhibit anxiety/depression-like behavior. A, ERK5 icKO mice are impaired in remote memory when the erk5 gene was inducibly deleted. Data are from Figure 2 of Pan et al. (2012a). **p < 0.01. B, C, These mice are not deficient in a dark/light exploration test (B) or tail-suspension test (C), performed sequentially after the remote memory test. n.s., Not significant.

Mentions: The behavior data in Figures 4-13 suggest that impaired adult neurogenesis does not lead to anxiety/depression-like behaviors. Since these data are all negative, we performed another set of experiments using a fourth cohort of ERK5 icKO mice, which had been subjected to hippocampus-dependent learning and memory behavior tests. In addition, ERK5loxP/loxP littermates similarly treated with tamoxifen or vehicle were added as genotype controls. The ERK5 icKO mice showed reduced remote contextual fear memory (Pan et al., 2012a) (Fig. 14A) (p = 0.0005534, p = 0.01635, and p = 0.01036 for percent freezing on a 5 week test, when ERK5 icKO mice were compared with control A, B, and C, mice respectively). However, they showed no change in the dark/light box test (Fig. 14B) and tail-suspension test (Fig. 14C) compared to all three groups of control mice, including genotype controls and tamoxifen drug controls (p = 0.43637, p = 0.98038, and p = 0.76539 for time in light, and p = 0.92040, p = 0.98541, and p = 0.95242 for light entries in the dark/light box test; p = 0.58043, p = 0.79644, and p = 0.76945 for immobile latency, and p = 0.71446, p = 0.66547 and p = 0.58948 for the immobile episodes in the tail-suspension test when ERK5 icKO mice were compared with control A, B, and C mice, respectively).


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)

The same cohort of ERK5 icKO mice that show impaired hippocampus-dependent memory do not exhibit anxiety/depression-like behavior. A, ERK5 icKO mice are impaired in remote memory when the erk5 gene was inducibly deleted. Data are from Figure 2 of Pan et al. (2012a). **p < 0.01. B, C, These mice are not deficient in a dark/light exploration test (B) or tail-suspension test (C), performed sequentially after the remote memory test. n.s., Not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 14: The same cohort of ERK5 icKO mice that show impaired hippocampus-dependent memory do not exhibit anxiety/depression-like behavior. A, ERK5 icKO mice are impaired in remote memory when the erk5 gene was inducibly deleted. Data are from Figure 2 of Pan et al. (2012a). **p < 0.01. B, C, These mice are not deficient in a dark/light exploration test (B) or tail-suspension test (C), performed sequentially after the remote memory test. n.s., Not significant.
Mentions: The behavior data in Figures 4-13 suggest that impaired adult neurogenesis does not lead to anxiety/depression-like behaviors. Since these data are all negative, we performed another set of experiments using a fourth cohort of ERK5 icKO mice, which had been subjected to hippocampus-dependent learning and memory behavior tests. In addition, ERK5loxP/loxP littermates similarly treated with tamoxifen or vehicle were added as genotype controls. The ERK5 icKO mice showed reduced remote contextual fear memory (Pan et al., 2012a) (Fig. 14A) (p = 0.0005534, p = 0.01635, and p = 0.01036 for percent freezing on a 5 week test, when ERK5 icKO mice were compared with control A, B, and C, mice respectively). However, they showed no change in the dark/light box test (Fig. 14B) and tail-suspension test (Fig. 14C) compared to all three groups of control mice, including genotype controls and tamoxifen drug controls (p = 0.43637, p = 0.98038, and p = 0.76539 for time in light, and p = 0.92040, p = 0.98541, and p = 0.95242 for light entries in the dark/light box test; p = 0.58043, p = 0.79644, and p = 0.76945 for immobile latency, and p = 0.71446, p = 0.66547 and p = 0.58948 for the immobile episodes in the tail-suspension test when ERK5 icKO mice were compared with control A, B, and C mice, respectively).

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