The hippocampal neuroproteome with aging and cognitive decline: past progress and future directions
- Department of Pharmacology, Penn State College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, USA
Although steady progress on understanding brain aging has been made over recent decades through standard anatomical, immunohistochemical, and biochemical techniques, the biological basis of non-neurodegenerative cognitive decline with aging remains to be determined. This is due in part to technical limitations of traditional approaches, in which only a small fraction of neurobiologically relevant proteins, mRNAs or metabolites can be assessed at a time. With the development and refinement of proteomic technologies that enable simultaneous quantitative assessment of hundreds to thousands of proteins, neuroproteomic studies of brain aging and cognitive decline are becoming more widespread. This review focuses on the contributions of neuroproteomic investigations to advances in our understanding of age-related deficits of hippocampus-dependent spatial learning and memory. Accumulating neuroproteomic data demonstrate that hippocampal aging involves common themes of dysregulated metabolism, increased oxidative stress, altered protein processing, and decreased synaptic function. Additionally, growing evidence suggests that cognitive decline does not represent a “more aged” phenotype, but rather is associated with specific neuroproteomic changes that occur in addition to age-related alterations. Understanding if and how age-related changes in the hippocampal neuroproteome contribute to cognitive decline and elucidating the pathways and processes that lead to cognitive decline are critical objectives that remain to be achieved. Progress in the field and challenges that remain to be addressed with regard to animal models, behavioral testing, and proteomic reporting are also discussed.
Keywords: proteome, aging, cognitive decline, learning and memory, brain, hippocampus
Citation: VanGuilder H. D. and Freeman W. M (2011) The hippocampal neuroproteome with aging and cognitive decline: past progress and future directions. Front. Ag. Neurosci. 3:8. doi: 10.3389/fnagi.2011.00008
Received: 06 January 2011; Accepted: 12 May 2011;
Published online: 23 May 2011.
Edited by:Emil C. Toescu, Birmingham University, UK
Reviewed by:Junming Wang, University of Mississippi Medical Center, USA
Lori Lynn Mcmahon, University of Alabama, USA
Aurel Popa Wagner, University of Greifswald, Germany
Copyright: © 2011 VanGuilder and Freeman. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.
*Correspondence: Willard M. Freeman, Department of Pharmacology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA. e-mail: firstname.lastname@example.org