Hippocampal expression of myelin-associated inhibitors is induced with age-related cognitive decline and correlates with deficits of spatial learning and memory.

Impairment of cognitive functions including hippocampus-dependent spatial learning and memory affects nearly half of the aged population. Age-related cognitive decline is associated with synaptic dysfunction that occurs in the absence of neuronal cell loss, suggesting that impaired neuronal signaling and plasticity may underlie age-related deficits of cognitive function. Expression of myelin-associated inhibitors (MAIs) of synaptic plasticity, including the ligands myelin-associated glycoprotein, neurite outgrowth inhibitor A, and oligodendrocyte myelin glycoprotein, and their common receptor, Nogo-66 receptor, was examined in hippocampal synaptosomes and Cornu ammonis area (CA)1, CA3 and dentate gyrus subregions derived from adult (12-13 months) and aged (26-28 months) Fischer 344 × Brown Norway rats.

Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment.

Background: Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline.

The hippocampal neuroproteome with aging and cognitive decline: past progress and future directions.

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.

Age-related alterations in retinal neurovascular and inflammatory transcripts.

Purpose: Vision loss is one of the most common complications of aging, even in individuals with no diagnosed ocular disease. Increasing age induces structural alterations and functional impairments in retinal neurons and microvasculature linked to the activation of proinflammatory signaling pathways. Commonalities between the effects of aging and those observed with diabetes, including visual impairment, vascular dysfunction, and increased inflammatory response, have led to the hypothesis that diabetes-associated pathologies reflect an "advanced aging" phenotype.

Chronic insulin treatment of diabetes does not fully normalize alterations in the retinal transcriptome.

Background: Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. Approximately 95% of patients with Type 1 diabetes develop some degree of retinopathy within 25 years of diagnosis despite normalization of blood glucose by insulin therapy. The goal of this study was to identify molecular changes in the rodent retina induced by diabetes that are not normalized by insulin replacement and restoration of euglycemia.

Hippocampal dysregulation of synaptic plasticity-associated proteins with age-related cognitive decline.

Age-related cognitive decline occurs without frank neurodegeneration and is the most common cause of memory impairment in aging individuals. With increasing longevity, cognitive deficits, especially in hippocampus-dependent memory processes, are increasing in prevalence. Nevertheless, the neurobiological basis of age-related cognitive decline remains unknown.

Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration.

Objective diagnostics of excessive alcohol use are valuable tools in the identification and monitoring of subjects with alcohol use disorders. A number of potential biomarkers of alcohol intake have been proposed, but none have reached widespread clinical usage, often due to limited diagnostic sensitivity and specificity. In order to identify novel potential biomarkers, we performed proteomic biomarker target discovery in plasma samples from non-human primates that chronically self-administer high levels of ethanol.

Multi-modal proteomic analysis of retinal protein expression alterations in a rat model of diabetic retinopathy.

Background: As a leading cause of adult blindness, diabetic retinopathy is a prevalent and profound complication of diabetes. We have previously reported duration-dependent changes in retinal vascular permeability, apoptosis, and mRNA expression with diabetes in a rat model system. The aim of this study was to identify retinal proteomic alterations associated with functional dysregulation of the diabetic retina to better understand diabetic retinopathy pathogenesis and that could be used as surrogate endpoints in preclinical drug testing studies.

Clinical application for the preservation of phospho-proteins through in-situ tissue stabilization.

Background: Protein biomarkers will play a pivotal role in the future of personalized medicine for both diagnosis and treatment decision-making. While the results of several pre-clinical and small-scale clinical studies have demonstrated the value of protein biomarkers, there have been significant challenges to translating these findings into routine clinical care. Challenges to the use of protein biomarkers include inter-sample variability introduced by differences in post-collection handling and ex vivo degradation of proteins and protein modifications.

Aging alters the expression of neurotransmission-regulating proteins in the hippocampal synaptoproteome.

Decreased cognitive performance reduces independence and quality of life for aging individuals. Healthy brain aging does not involve significant neuronal loss, but little is known about the effects of aging at synaptic terminals. Age-related cognitive decline likely reflects the manifestation of dysregulated synaptic function and ineffective neurotransmission.

The use of neuroproteomics in drug abuse research.

The number of discovery proteomic studies of drug abuse has begun to increase in recent years, facilitated by the adoption of new techniques such as 2D-DIGE and iTRAQ. For these new tools to provide the greatest insight into the neurobiology of addiction, however, it is important that the addiction field has a clear understanding of the strengths, limitations, and drug abuse-specific research factors of neuroproteomic studies. This review outlines approaches for improving animal models, protein sample quality and stability, proteome fractionation, data analysis, and data sharing to maximize the insights gained from neuroproteomic studies of drug abuse.

Diabetes downregulates presynaptic proteins and reduces basal synapsin I phosphorylation in rat retina.

Diabetic retinopathy can result in vision loss and involves progressive neurovascular degeneration of the retina. This study tested the hypothesis that diabetes decreases the retinal expression of presynaptic proteins involved in synaptic function. The protein and mRNA contents for synapsin I, synaptophysin, vesicle-associated membrane protein 2, synaptosomal-associated protein of 25 kDa and postsynaptic density protein of 95 kDa were measured by immunohistochemistry, immunoblotting and real-time quantitative polymerase chain reaction in whole retinas and retinal synaptosomes from streptozotocin-diabetic and control Sprague-Dawley rats.

Twenty-five years of quantitative PCR for gene expression analysis.

Following its invention 25 years ago, PCR has been adapted for numerous molecular biology applications. Gene expression analysis by reverse-transcription quantitative PCR (RT-qPCR) has been a key enabling technology of the post-genome era. Since the founding of BioTechniques, this journal has been a resource for the improvements in qPCR technology, experimental design, and data analysis.

Catecholase activity associated with copper-S100B.

This study addresses the spectroscopic properties and reactivity associated with the copper-loaded form of S100B isolated from bovine brain. Copper(II)-S100B displays EPR features typical of a type II copper center and is shown here to exhibit catecholase activity, the two-electron oxidation of catechols. The steady-state kinetics associated with the oxidation of several catecholamines has been probed in order to further characterize this activity.