Early endosome antigen 1 (Endosome-associated protein p162) (Zinc finger FYVE domain-containing protein 2) [ZFYVE2]

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Quantitative Immunoblotting Analyses Reveal that the Abundance of Actin, Tubulin, Synaptophysin and EEA1 Proteins is Altered in the Brains of Aged Mice.

Optimal synaptic activity is essential for cognitive function, including memory and learning. Evidence indicates that cognitive decline in elderly individuals is associated with altered synaptic function. However, the impact of aging on the expression of neurotransmitter receptors and accessory proteins in brain synapses remains unclear. To fill this knowledge gap, we investigated the effect of aging on the mouse brain by utilizing a subcellular brain tissue fractionation procedure to measure protein abundance using quantitative Western Blotting. Comparing 7-month- (control) and 22-month- (aged) old mouse tissue, no significant differences were identified in the levels of AMPA receptor subunits between the experimental groups. The abundance of GluN2B NMDA receptor subunits decreased in aged mice, whereas the levels of GluN2A did not change. The analysis of cytoskeletal proteins showed an altered level of actin and tubulin in aged mice while PSD-95 protein did not change. Vesicle protein analysis revealed that synaptophysin abundance is decreased in older brains whereas EEA1 was significantly increased. Thus, our results suggest that physiological aging profoundly impacts the abundance of molecules associated with neurotransmitter release and vesicle cycling, proteins implicated in cognitive function.


Keywords

  • aging
  • brain
  • cortex
  • glutamate receptor
  • synapse
  • vesicle


Hippocampal signaling cascades are modulated in voluntary and treadmill exercise rats.

Systematic protein expression studies in the brain of exercising and sedentary animals have not been carried out for far. Signaling proteins are main structures regulating hippocampal function and we decided to determine differences in signaling protein levels in rat hippocampus by a proteomic approach. Aged, male Sprague-Dawley rats, 23 months old, were used for the study: the first group consisted of sedentary rats, the second of rats with voluntary exercise from 5 to 23 months and the third was performing involuntary exercise on a treadmill from 5 to 23 months. 2-DE with subsequent mass spectrometrical identification of spots followed by quantification of spots was carried out. Annexin A5, A3, phosphatidylethanolamine-binding protein, guanine nucleotide-binding protein G(I)/G(S)/G(T), 14-3-3 protein gamma, 14-3-3 protein zeta/delta, prohibitin, visinin-like 1, protein phosphatase 1, septin 8, phosphoprotein enriched in astrocytes 15, transcription factor Pur-beta, EEA1 protein, SH3 domain-binding glutamic acid-rich-like protein 2, and cell division cycle 42 showed differential protein levels in the three groups. These results form the basis for functional studies elucidating mechanisms and links between exercise and hippocampal signaling and function.

MeSH Terms

  • Aging
  • Animals
  • Behavior
  • Brain Chemistry
  • Calcium-Binding Proteins
  • Electrophoresis, Gel, Two-Dimensional
  • Exercise Test
  • Gene Expression Regulation
  • Hippocampus
  • Intracellular Signaling Peptides and Proteins
  • Isoelectric Focusing
  • Male
  • Nerve Tissue Proteins
  • Phosphorylation
  • Physical Conditioning, Animal
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Spectrometry, Mass, Electrospray Ionization