Proteomic investigation of the hippocampus in prenatally stressed mice implicates changes in membrane trafficking, cytoskeletal, and metabolic function.
Prenatal stress influences the development of the fetal brain and so contributes to the risk of the development of psychiatric disorders in later life. The hippocampus is particularly sensitive to prenatal stress, and robust abnormalities have been described in the hippocampus in schizophrenia and depression. The aim of this study was to determine whether prenatal stress is associated with distinct patterns of differential protein expression in the hippocampus using a validated mouse model. We therefore performed a comparative proteomic study assessing female hippocampal samples from 8 prenatally stressed mice and 8 control mice. Differential protein expression was assessed using 2-dimensional difference in gel electrophoresis and subsequent mass spectrometry. The observed changes in a selected group of differentially expressed proteins were confirmed by Western blotting. In comparison to controls, 47 protein spots (38 individual proteins) were found to be differentially expressed in the hippocampus of prenatally stressed mice. Functional grouping of these proteins revealed that prenatal stress influenced the expression of proteins involved in brain development, cytoskeletal composition, stress response, and energy metabolism. Western blotting was utilized to validate the changes in calretinin, hippocalcin, profilin-1 and the signal-transducing adaptor molecule STAM1. Septin-5 could not be validated via Western blotting due to methodological issues. Closer investigation of the validated proteins also pointed to an interesting role for membrane trafficking deficits mediated by prenatal stress. Our findings demonstrate that prenatal stress leads to altered hippocampal protein expression, implicating numerous molecular pathways that may provide new targets for psychotropic drug development.
We thank Caitriona Scaife, BSc, for technical assistance in 2D-DIGE image analysis. Access to and use of mass spectrometry instrumentation of the Conway Institute is gratefully acknowledged; Giuliano Elia, PhD, Cathy Rooney, BSc, and Kasper Pedersen, BSc provided technical assistance in mass spectrometry. This work was supported by the Irish Health Research Board, Science Foundation Ireland, The Brain and Behavior Research Foundation (formerly NARSAD), and the Stanley Medical Research Institute.
CommentsThe final, published version of this article is available at https://www.karger.com/Article/Abstract/365327
Published CitationFöcking M, Opstelten R, Prickaerts J, Steinbusch HW, Dunn MJ, van den Hove DL, Cotter DR. Proteomic investigation of the hippocampus in prenatally stressed mice implicates changes in membrane trafficking, cytoskeletal, and metabolic function. Developmental Neuroscience. 2014;36(5):432-42
- Beaumont Hospital