Age-related differences in the dynamics of hippocampal proteasome recovery

• Published in: Journal of neurochemistry 2012-11, Vol.123 (4), p.635-644
• Main Authors: Gavilán, M. Paz, Pintado, Cristina, Gavilán, Elena, García-Cuervo, Luisa M., Castaño, Angelica, Ríos, Rosa M., Ruano, Diego
• Format: Article
• Language: English
• Subjects: Age Factors; Aging; Animals; Biological and medical sciences; Brain research; Catalytic Domain - physiology; Cell Nucleolus - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; hippocampus; Hippocampus - cytology; Hippocampus - metabolism; immunoproteasome; Immunoproteins - metabolism; Indexing in process; Male; Medical sciences; Neurochemistry; neurodegen-eration; Neurology; Neurons - cytology; Neurons - metabolism; POMP; proteasome; Proteasome Endopeptidase Complex - metabolism; Rats; Rats, Wistar; Stress; Testing laboratories; ubiquitin; Up-Regulation - physiology; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2012.07932.x

Regulation of proteasome abundance to meet cell needs under stress conditions is critical for maintaining cellular homeostasis. However, the effects of aging on this homeostatic response remain unknown. In this report, we analyzed in young and aged rat hippocampus, the dynamics of proteasome recovery induced by proteasome stress. Proteasome inhibition in young rats leads to an early and coordinate transcriptional and translational up‐regulation of both the catalytic subunits of constitutive proteasome and the proteasome maturation protein. By contrast, aged rats up‐regulated the inducible catalytic subunits and showed a lower and shorter expression of proteasome maturation protein. This resulted in a faster recovery of proteasome activity in young rats. Importantly, proteasome inhibition highly affected pyramidal cells, leading to the accumulation of ubiquitinated proteins in perinuclear regions of aged, but not young pyramidal neurons. These data strongly suggest that age‐dependent differences in proteasome level and composition could contribute to neurodegeneration induced by proteasome dysfunction in normal and pathological aging. Proteasome regulation is critical to hippocampal homeostasis. Here, we show that young rats strongly increase the biogenesis of constitutive proteasomes, whereas aged rats moderately increase the biogenesis of immunoproteasome. Proteasome inhibition highly affected pyramidal cells, leading to the accumulation of ubiquitinated proteins in perinuclear regions of aged, but not young pyramidal neurons. The lower capacity to maintain proteasome homeostasis could represent an additional factor contributing to hippocampal neurodegeneration.