Age-related modifications of egr1 expression and ubiquitin-proteasome components in pet dog hippocampus.

In this paper we examined the impact of age on cognitive functions and the age-related modifications of egr1 expression, an inducible transcription factor with a confirmed role in synaptic plasticity and regulation of the proteasome activity, on pet dogs. Additionally, we examined the age-related changes of some elements of the ubiquitin-proteasome system, which is the apparatus that prevents the intracellular accumulation of abnormal proteins. The results of behavioral analysis revealed that old/senior dogs (9–16-year-old) had impaired cognitive performance compared to young/middle-aged dogs (2–8-year-old) in the Reversal Learning task. Taken togheter, the results (age-related decline of Psmd4, Psmb8, CHIP, and egr1 expression; increase of Psmb9 and Hsp90 expression) suggest that the activity of the ubiquitin-proteasome system in the dog hippocampus is a multi-step process, in which abnormal proteins destined for degradation are recognized and destroyed, and shows an age-related decline. The consequent failure of the “protein quality control system” might have detrimental effects on cell physiology and lead to a progressive impairment of cognitive functions.