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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 display enhanced hypophagia behavior in a novelty-suppressed feeding test. After 4 d of food restriction, individually housed mice were introduced into an unfamiliar environment with one pellet of regular mouse food. A, Latency to eat the food pellet in the unfamiliar environment. B, Food consumption in the home cage. Once the mouse started eating the food or the 15 min time limit was reached, the mouse and a new preweighed food pellet were quickly transferred to the home cage and the food consumption in the next 5 min was measured. n.s., Not significant.
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Figure 7: ERK5 icKO mice do not display enhanced hypophagia behavior in a novelty-suppressed feeding test. After 4 d of food restriction, individually housed mice were introduced into an unfamiliar environment with one pellet of regular mouse food. A, Latency to eat the food pellet in the unfamiliar environment. B, Food consumption in the home cage. Once the mouse started eating the food or the 15 min time limit was reached, the mouse and a new preweighed food pellet were quickly transferred to the home cage and the food consumption in the next 5 min was measured. n.s., Not significant.

Mentions: Feeding in a new environment is an indication of adaptation, whereas the inhibition or delay of feeding behavior in a new environment, hypophagia, is a sign of anxiety (Dulawa and Hen, 2005). One commonly used hypophagia test is novelty-suppressed feeding, in which a food-deprived mouse is introduced to a new environment with a pellet of food and the latency to feed is quantified. Compared with the vehicle control mice, ERK5 icKO mice did not delay their first attempt to eat food (p = 0.212)13 (Fig. 7A). However, a confounding factor for this test is the animal’s degree of hunger and level of appetite, which may affect their motivation for food, thus the latency to feed. Therefore, food consumption in a familiar environment, in their home cages, to which they were returned after the test, was used to assess their motivation for food. There was no significant difference between ERK5 icKO mice and the control mice in their home cage food consumption (p = 0.545)14 (Fig. 7B). Together, these data suggest that ERK5 icKO mice do not display an elevated level of hypophagia, indicating that they do not have an increased level of anxiety in the novelty-suppressed feeding test.


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 display enhanced hypophagia behavior in a novelty-suppressed feeding test. After 4 d of food restriction, individually housed mice were introduced into an unfamiliar environment with one pellet of regular mouse food. A, Latency to eat the food pellet in the unfamiliar environment. B, Food consumption in the home cage. Once the mouse started eating the food or the 15 min time limit was reached, the mouse and a new preweighed food pellet were quickly transferred to the home cage and the food consumption in the next 5 min was measured. n.s., Not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: ERK5 icKO mice do not display enhanced hypophagia behavior in a novelty-suppressed feeding test. After 4 d of food restriction, individually housed mice were introduced into an unfamiliar environment with one pellet of regular mouse food. A, Latency to eat the food pellet in the unfamiliar environment. B, Food consumption in the home cage. Once the mouse started eating the food or the 15 min time limit was reached, the mouse and a new preweighed food pellet were quickly transferred to the home cage and the food consumption in the next 5 min was measured. n.s., Not significant.
Mentions: Feeding in a new environment is an indication of adaptation, whereas the inhibition or delay of feeding behavior in a new environment, hypophagia, is a sign of anxiety (Dulawa and Hen, 2005). One commonly used hypophagia test is novelty-suppressed feeding, in which a food-deprived mouse is introduced to a new environment with a pellet of food and the latency to feed is quantified. Compared with the vehicle control mice, ERK5 icKO mice did not delay their first attempt to eat food (p = 0.212)13 (Fig. 7A). However, a confounding factor for this test is the animal’s degree of hunger and level of appetite, which may affect their motivation for food, thus the latency to feed. Therefore, food consumption in a familiar environment, in their home cages, to which they were returned after the test, was used to assess their motivation for food. There was no significant difference between ERK5 icKO mice and the control mice in their home cage food consumption (p = 0.545)14 (Fig. 7B). Together, these data suggest that ERK5 icKO mice do not display an elevated level of hypophagia, indicating that they do not have an increased level of anxiety in the novelty-suppressed feeding test.

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