Limits...
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 MAPK expression in the dentate gyrus of the adult mouse brain. Images are representative immunostaining of coronal sections of adult mouse brain tissue showing ERK5 protein expression (green) primarily in transiently amplifying progenitors and/or newborn neurons (doublecortin+ (DCX) or NCAM+) but not in mature neurons (NeuN, red) in the SGZ. Hoechst staining (blue) was used to identify all cell nuclei. Scale bar represents 100 μm and applies to all panels.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4596085&req=5

Figure 2: ERK5 MAPK expression in the dentate gyrus of the adult mouse brain. Images are representative immunostaining of coronal sections of adult mouse brain tissue showing ERK5 protein expression (green) primarily in transiently amplifying progenitors and/or newborn neurons (doublecortin+ (DCX) or NCAM+) but not in mature neurons (NeuN, red) in the SGZ. Hoechst staining (blue) was used to identify all cell nuclei. Scale bar represents 100 μm and applies to all panels.

Mentions: Under normal conditions, ERK5 expression in the adult brain is limited to the neural stem/progenitor cells, transiently amplifying progenitors, and/or newborn neurons in the adult neurogenic regions including the subgranular zone (SGZ) of the dentate gyrus in the hippocampus and the subventricular zone/rostral migratory stream. ERK5 is not expressed in mature neurons (NeuN+) in the adult brain (Pan et al., 2012c; Pan et al., 2012d; Li et al., 2013; Wang et al., 2013). Data in Figure 2 confirm that ERK5 protein is specifically expressed along the SGZ of the dentate gyrus, and that it is colabeled with markers for transiently amplifying progenitors and/or newborn neurons (PSA-NCAM, DCX), but not with NeuN, a marker expressed in mature neurons.


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 MAPK expression in the dentate gyrus of the adult mouse brain. Images are representative immunostaining of coronal sections of adult mouse brain tissue showing ERK5 protein expression (green) primarily in transiently amplifying progenitors and/or newborn neurons (doublecortin+ (DCX) or NCAM+) but not in mature neurons (NeuN, red) in the SGZ. Hoechst staining (blue) was used to identify all cell nuclei. Scale bar represents 100 μm and applies to all panels.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: ERK5 MAPK expression in the dentate gyrus of the adult mouse brain. Images are representative immunostaining of coronal sections of adult mouse brain tissue showing ERK5 protein expression (green) primarily in transiently amplifying progenitors and/or newborn neurons (doublecortin+ (DCX) or NCAM+) but not in mature neurons (NeuN, red) in the SGZ. Hoechst staining (blue) was used to identify all cell nuclei. Scale bar represents 100 μm and applies to all panels.
Mentions: Under normal conditions, ERK5 expression in the adult brain is limited to the neural stem/progenitor cells, transiently amplifying progenitors, and/or newborn neurons in the adult neurogenic regions including the subgranular zone (SGZ) of the dentate gyrus in the hippocampus and the subventricular zone/rostral migratory stream. ERK5 is not expressed in mature neurons (NeuN+) in the adult brain (Pan et al., 2012c; Pan et al., 2012d; Li et al., 2013; Wang et al., 2013). Data in Figure 2 confirm that ERK5 protein is specifically expressed along the SGZ of the dentate gyrus, and that it is colabeled with markers for transiently amplifying progenitors and/or newborn neurons (PSA-NCAM, DCX), but not with NeuN, a marker expressed in mature neurons.

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