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Neurabin in the anterior cingulate cortex regulates anxiety-like behavior in adult mice.

Kim SS, Wang H, Li XY, Chen T, Mercaldo V, Descalzi G, Wu LJ, Zhuo M - Mol Brain (2011)

Bottom Line: Absence of neurabin, a cytoskeletal protein, resulted in reduced anxiety-like behavior and increased depression-like behavior.Furthermore, loss of neurabin increased the presynaptic release of glutamate and cingulate neuronal excitability.These findings reveal novel roles of the ACC in anxiety disorders, and provide a new therapeutic target for the treatment of anxiety disorders.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto Centre for the Study of Pain, ON, Canada.

ABSTRACT
Affective disorders, which include anxiety and depression, are highly prevalent and have overwhelming emotional and physical symptoms. Despite human brain imaging studies, which have implicated the prefrontal cortex including the anterior cingulate cortex (ACC), little is known about the ACC in anxiety disorders. Here we show that the ACC does modulate anxiety-like behavior in adult mice, and have identified a protein that is critical for this modulation. Absence of neurabin, a cytoskeletal protein, resulted in reduced anxiety-like behavior and increased depression-like behavior. Selective inhibition of neurabin in the ACC reproduced the anxiety but not the depression phenotype. Furthermore, loss of neurabin increased the presynaptic release of glutamate and cingulate neuronal excitability. These findings reveal novel roles of the ACC in anxiety disorders, and provide a new therapeutic target for the treatment of anxiety disorders.

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Neurabin siRNA in primary cortical neuron culture. A, Reduction of relative neurabin levels in primary cortical neuron culture by neurabin siRNA.
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Figure 5: Neurabin siRNA in primary cortical neuron culture. A, Reduction of relative neurabin levels in primary cortical neuron culture by neurabin siRNA.

Mentions: It is difficult to determine the precise regions of the brain that contribute to anxiety in neurabin KO mice since the gene is deleted globally. Furthermore, potential developmental defects or compensatory changes cannot be ruled out. Therefore, using focal application of neurabin siRNA, we investigated whether the inhibition of neurabin expression in the ACC would modulate anxiety-like behavior. First, to confirm the effectiveness of the siRNA, primary cortical neuron culture at DIV 10 was transfected with siRNA negative control or neurabin siRNA (Invitrogen, CA). The expression of neurabin was then measured by Western blot at 48 h after transfection. We found that neurabin siRNA reduced the relative neurabin levels by approximately 70% (Figure 5A). We also saw reduction in neurabin levels when mice were given injections of neurabin siRNA into the ACC for 3 consecutive days (data not shown).


Neurabin in the anterior cingulate cortex regulates anxiety-like behavior in adult mice.

Kim SS, Wang H, Li XY, Chen T, Mercaldo V, Descalzi G, Wu LJ, Zhuo M - Mol Brain (2011)

Neurabin siRNA in primary cortical neuron culture. A, Reduction of relative neurabin levels in primary cortical neuron culture by neurabin siRNA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3037880&req=5

Figure 5: Neurabin siRNA in primary cortical neuron culture. A, Reduction of relative neurabin levels in primary cortical neuron culture by neurabin siRNA.
Mentions: It is difficult to determine the precise regions of the brain that contribute to anxiety in neurabin KO mice since the gene is deleted globally. Furthermore, potential developmental defects or compensatory changes cannot be ruled out. Therefore, using focal application of neurabin siRNA, we investigated whether the inhibition of neurabin expression in the ACC would modulate anxiety-like behavior. First, to confirm the effectiveness of the siRNA, primary cortical neuron culture at DIV 10 was transfected with siRNA negative control or neurabin siRNA (Invitrogen, CA). The expression of neurabin was then measured by Western blot at 48 h after transfection. We found that neurabin siRNA reduced the relative neurabin levels by approximately 70% (Figure 5A). We also saw reduction in neurabin levels when mice were given injections of neurabin siRNA into the ACC for 3 consecutive days (data not shown).

Bottom Line: Absence of neurabin, a cytoskeletal protein, resulted in reduced anxiety-like behavior and increased depression-like behavior.Furthermore, loss of neurabin increased the presynaptic release of glutamate and cingulate neuronal excitability.These findings reveal novel roles of the ACC in anxiety disorders, and provide a new therapeutic target for the treatment of anxiety disorders.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto Centre for the Study of Pain, ON, Canada.

ABSTRACT
Affective disorders, which include anxiety and depression, are highly prevalent and have overwhelming emotional and physical symptoms. Despite human brain imaging studies, which have implicated the prefrontal cortex including the anterior cingulate cortex (ACC), little is known about the ACC in anxiety disorders. Here we show that the ACC does modulate anxiety-like behavior in adult mice, and have identified a protein that is critical for this modulation. Absence of neurabin, a cytoskeletal protein, resulted in reduced anxiety-like behavior and increased depression-like behavior. Selective inhibition of neurabin in the ACC reproduced the anxiety but not the depression phenotype. Furthermore, loss of neurabin increased the presynaptic release of glutamate and cingulate neuronal excitability. These findings reveal novel roles of the ACC in anxiety disorders, and provide a new therapeutic target for the treatment of anxiety disorders.

Show MeSH
Related in: MedlinePlus