MHC class I, beta2 microglobulin, and the INF-gamma receptor are upregulated in aged motoneurons.
During aging, spinal cord motoneurons show characteristic changes including the loss of afferent boutons, a selective process that associates with gliosis and behavioral motor impairment. Evidence suggests that the major histocompatibility complex Class I (MHC I) system may be involved in synaptic plasticity of neurons during development and regeneration. In search of a mechanism governing senescent changes in synaptic connectivity, we report evidence for increased expression of MHC I and beta2 microglobulin (beta2M) in motoneurons and glial-like profiles of 30-month-old rats. The regulatory signal(s) for MHC I expression in normal neurons remains unresolved but among tentative molecules are cytokines such as interferon-gamma (INF-gamma) and tumor necrosis factor alpha (TNF-alpha). Interestingly, aged motoneurons, overlapping with those showing increased levels of MHC I, contained increased levels of INF-gamma receptor message. INF-gamma mRNA was detected at low levels in most (8/9) of the aged spinal cords but only infrequently (2/9) in young adult spinal cords; however, the cellular localization of INF-gamma mRNA could not be determined. Our data also indicates that TNF-alpha is upregulated in the senescent spinal cord but that TNF-alpha immunoreactive protein does not associate with motoneurons. We report evidence for an increased expression of MHC I and beta2M in senescent spinal motoneurons and discuss the possibility that this regulation associates with INF-gamma or changes in neurotrophin signaling and neuron activity in senescence.
Edström
Erik
E
Experimental Neurogerontology, Department of Neuroscience, Retzius Laboratory, Karolinska Institutet, Stockholm, Sweden.
Kullberg
Susanna
S
Ming
Yu
Y
Zheng
Huaiyu
H
Ulfhake
Brun
B
D000375:Aging / Q000502:physiology*; D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017471:Receptors, Interferon / Q000235:genetics*; D013116:Spinal Cord / Q000254:growth & development / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000235:genetics*; D000096743:Interferon gamma Receptor
D015395:Histocompatibility Antigens Class I; D017471:Receptors, Interferon; D001613:beta 2-Microglobulin; D000096743:Interferon gamma Receptor