Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases. Via their effector LIM kinase (LIMK), RhoA and ras-related C3 botulinum toxin substrate 1 (RAC) GTPases phosphorylate and inhibit cofilin, an actin-depolymerizing molecule, favoring spine growth. Additionally, RhoA, through Rho kinase (ROCK), inactivates myosin phosphatase through phosphorylation of the myosin-binding subunit (MYPT1), producing actomyosin contraction and probable spine loss. Some micro-RNAs negatively control the translation of specific mRNAs involved in Rho GTPase signaling. For example, miR-138 indirectly activates RhoA, and miR-134 reduces LIMK1 levels, resulting in spine shrinkage; in contrast, miR-132 activates RAC1, promoting spine formation. We evaluated whether N-cadherin/β-catenin and Rho signaling is sensitive to chronic restraint stress. Stressed rats exhibit anhedonia, impaired associative learning, and immobility in the forced swim test and reduction in N-cadherin levels but not β-catenin in the hippocampus. We observed a reduction in spine number in the apical dendrites of CA1 pyramidal neurons, with no effect on the levels of miR-132 or miR-134. Although the stress did not modify the RAC-LIMK-cofilin signaling pathway, we observed increased phospho-MYPT1 levels, probably mediated by RhoA-ROCK activation. Furthermore, chronic stress raises the levels of miR-138 in accordance with the observed activation of the RhoA-ROCK pathway. Our findings suggest that a dysregulation of RhoA-ROCK activity by chronic stress could potentially underlie spine loss in hippocampal neurons.
Pubmed ID: 26010004 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This unknown targets Cofilin, phospho (Ser3)
View all literature mentionsThis polyclonal targets Phospho-MYPT1 (Thr853)
View all literature mentionsThis unknown targets LIM Kinase 1
View all literature mentionsThis unknown targets MYPT1
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis polyclonal targets Cofilin
View all literature mentionsThis monoclonal targets Cadherin, N
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets CTNNB1
View all literature mentionsThis polyclonal targets R-Y-PT-V-V
View all literature mentionsData analytics software to compute statistical power analyses for many commonly used statistical tests in social and behavioral research. It can also be used to compute effect sizes and to graphically display the results of power analyses.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsDigitizer software which can convert graph images to useful (x,y) data by turning a scanner into an automatic graph digitizer. UN‑SCAN‑IT works with most image formats (TIFF, JPG, BMP, GIF, etc.) from any scanner, digital camera, or other image source to digitize plots, instrumental output, published graphs, etc. Its features include: automatically digitizing strip chart and xy recorder output, digitizing graphs that are on different scales to compare results, comparing data with published graphs of other investigators, digitizing old plots and charts for comparison with new data, and re‑scaling and appending existing printed graphs.
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis unknown targets Cofilin, phospho (Ser3)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Cofilin
View all literature mentionsThis unknown targets MYPT1
View all literature mentionsThis polyclonal targets CTNNB1
View all literature mentionsThis unknown targets LIM Kinase 1
View all literature mentionsThis polyclonal targets R-Y-PT-V-V
View all literature mentionsThis monoclonal targets Cadherin, N
View all literature mentionsData analytics software to compute statistical power analyses for many commonly used statistical tests in social and behavioral research. It can also be used to compute effect sizes and to graphically display the results of power analyses.
View all literature mentionsDigitizer software which can convert graph images to useful (x,y) data by turning a scanner into an automatic graph digitizer. UN‑SCAN‑IT works with most image formats (TIFF, JPG, BMP, GIF, etc.) from any scanner, digital camera, or other image source to digitize plots, instrumental output, published graphs, etc. Its features include: automatically digitizing strip chart and xy recorder output, digitizing graphs that are on different scales to compare results, comparing data with published graphs of other investigators, digitizing old plots and charts for comparison with new data, and re‑scaling and appending existing printed graphs.
View all literature mentionsThis polyclonal targets Phospho-MYPT1 (Thr853)
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentions