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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 increased despair behavior in a tail-suspension test. A, Latency to the first episode of immobility. B, Total number of episodes of immobility. C, Accumulated duration of immobility. n.s., Not significant.
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Figure 12: ERK5 icKO mice do not show increased despair behavior in a tail-suspension test. A, Latency to the first episode of immobility. B, Total number of episodes of immobility. C, Accumulated duration of immobility. n.s., Not significant.

Mentions: To assess hopelessness, we subjected ERK5 icKO mice and control mice to the forced-swim and tail-suspension tests. In the forced-swim test, a mouse is placed into an inescapable container filled with water. After a brief period of vigorous swimming, the mouse exhibits a characteristic immobile posture. Early onset of immobility and an increased level of immobility indicate increased behavioral despair or lowered mood (Porsolt et al., 1977). Compared with controls, ERK5 icKO mice showed no signs of increased despair in the forced-swim test, determined by the latency to the first immobile episode (p = 0.192)23, the immobility frequency (p = 0.470)24, and the total time spent immobile (p = 0.191)25 (Fig. 11). In the tail-suspension test, the mice were hung on a bar by the tail for 6 min and immobility behavior was scored. The ERK5 icKO mice did not show earlier onset of immobility (p = 0.942)26, or increased frequency (p = 0.840)27 or duration of immobility (p = 0.389)28 (Fig. 12), signs of increased behavioral despair.


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 increased despair behavior in a tail-suspension test. A, Latency to the first episode of immobility. B, Total number of episodes of immobility. C, Accumulated duration of immobility. n.s., Not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4596085&req=5

Figure 12: ERK5 icKO mice do not show increased despair behavior in a tail-suspension test. A, Latency to the first episode of immobility. B, Total number of episodes of immobility. C, Accumulated duration of immobility. n.s., Not significant.
Mentions: To assess hopelessness, we subjected ERK5 icKO mice and control mice to the forced-swim and tail-suspension tests. In the forced-swim test, a mouse is placed into an inescapable container filled with water. After a brief period of vigorous swimming, the mouse exhibits a characteristic immobile posture. Early onset of immobility and an increased level of immobility indicate increased behavioral despair or lowered mood (Porsolt et al., 1977). Compared with controls, ERK5 icKO mice showed no signs of increased despair in the forced-swim test, determined by the latency to the first immobile episode (p = 0.192)23, the immobility frequency (p = 0.470)24, and the total time spent immobile (p = 0.191)25 (Fig. 11). In the tail-suspension test, the mice were hung on a bar by the tail for 6 min and immobility behavior was scored. The ERK5 icKO mice did not show earlier onset of immobility (p = 0.942)26, or increased frequency (p = 0.840)27 or duration of immobility (p = 0.389)28 (Fig. 12), signs of increased behavioral despair.

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