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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 exhibit enhanced depression after a 4 week course of CUS treatment. A, Latency to the first episode of immobility from the onset of the test, and the accumulated duration of immobility in the last 4 min of the forced-swim test. B, Latency of immobility, the total number of episodes of immobility, and the accumulated duration of immobility in the tail suspension test. n.s., Not significant.
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Figure 13: ERK5 icKO mice do not exhibit enhanced depression after a 4 week course of CUS treatment. A, Latency to the first episode of immobility from the onset of the test, and the accumulated duration of immobility in the last 4 min of the forced-swim test. B, Latency of immobility, the total number of episodes of immobility, and the accumulated duration of immobility in the tail suspension test. n.s., Not significant.

Mentions: Finally, we investigated whether impaired adult neurogenesis increases the animal’s susceptibility to depression in the context of chronic stress, using a modified CUS protocol. Stressors included food and water deprivation, cage tilt and wet bedding, cold swim and warm swim, electrical foot shock, tail pinch, and alteration of light/dark cycle with a randomized schedule for 4 weeks. Mice were then subjected to the forced-swim or tail-suspension tests to evaluate depression. There was no difference between ERK5 icKO and control mice in their latency to immobility (p = 0.389)29 and time spent immobile (p = 0.527)30 in the forced-swim test (Fig. 13A), and in their latency to immobility (p = 0.816)31, frequency of immobility (p = 0.694)32, and time spent in immobility (p = 0.771)33 in the tail-suspension test (Fig. 13B). These data indicate that the inhibition of adult neurogenesis by ERK5 deletion does not increase the animal’s susceptibility to depression induced by chronic unpredictable stress.


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 exhibit enhanced depression after a 4 week course of CUS treatment. A, Latency to the first episode of immobility from the onset of the test, and the accumulated duration of immobility in the last 4 min of the forced-swim test. B, Latency of immobility, the total number of episodes of immobility, and the accumulated duration of immobility in the tail suspension test. n.s., Not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 13: ERK5 icKO mice do not exhibit enhanced depression after a 4 week course of CUS treatment. A, Latency to the first episode of immobility from the onset of the test, and the accumulated duration of immobility in the last 4 min of the forced-swim test. B, Latency of immobility, the total number of episodes of immobility, and the accumulated duration of immobility in the tail suspension test. n.s., Not significant.
Mentions: Finally, we investigated whether impaired adult neurogenesis increases the animal’s susceptibility to depression in the context of chronic stress, using a modified CUS protocol. Stressors included food and water deprivation, cage tilt and wet bedding, cold swim and warm swim, electrical foot shock, tail pinch, and alteration of light/dark cycle with a randomized schedule for 4 weeks. Mice were then subjected to the forced-swim or tail-suspension tests to evaluate depression. There was no difference between ERK5 icKO and control mice in their latency to immobility (p = 0.389)29 and time spent immobile (p = 0.527)30 in the forced-swim test (Fig. 13A), and in their latency to immobility (p = 0.816)31, frequency of immobility (p = 0.694)32, and time spent in immobility (p = 0.771)33 in the tail-suspension test (Fig. 13B). These data indicate that the inhibition of adult neurogenesis by ERK5 deletion does not increase the animal’s susceptibility to depression induced by chronic unpredictable stress.

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