Abstracts (complete list) - Wissenschaft Online

Stephan Paxian, Markus P. Kummer, Lars Tatenhorst, Klaus Pfeffer, Frank Kirchhoff,
Roland Schmid, Michael T. Heneka
Effects of neuronal and microglial disrupted RelA(p65) in the
CNS during neuroinflammatory disorders
Proteins of the NF-κB/Rel family of transcription factors are ubiquitously expressed and
play a key role in a variety of physiological processes as acute phase, stress- and
immune response, cell cycle and apoptosis. In mammals, the NF-κB/Rel family
comprises five members, RelA (p65), RelB, c-Rel, NF-κB1 (p105/p50) and NF-κB2
(p100/p52). Its role in the immune system and host defence has been well defined over
the last decades. In contrast, our understanding of the function of this transcription
factors in the nervous system (NS) is only emerging. Recent reports decipher the
diverse functions of NF-κB in NS development and activity, which range from the control
of cell growth, survival and inflammatory response to synaptic plasticity, behavior and
cognition. Particular attention is given to the specific roles of NF-κB in the various cells
of the NS, e.g. neurons and glia as NF-κB participates to several neurodegenerative
disorders, such as Alzheimer´s, Parkinson´s and Multiple Sklerosis. To determine the
specific role of the NF-κB subunit RelA(p65) in the NS we generated conditional RelA
knockout mice using the Cre/lox-system to bypass the embryonic letality of mice with a
conventional inactivated RelA. Intercrossing these mouse line with mice expressing
either a neuronal (NEXC) or microglial (F4/80) specific Cre generates mice exhibiting a
specific deletion of RelA in the referring tissue. Current inspections determine the
efficiacy of the Cre specified RelA deletion in the CNS. In addition, histological analysis
show a clear tissue defined effect of a Cre induced RelA inactivation. Ongoing
experiments allocate the specific expression profiles and protein patterns of NF-κB/RelA
target genes of isolated primary neurons (NEXC) or microglia (F4/80) from mice with a
disrupted RelA in these cells. In addition, mouse models of neuroinflammatory disorders
as e.g. MPTP (Parkinson), intercrossed APP/PS1 mice (Alzheimer), EAE (experimental
autoimmune encephalomyelitis) and stroke should be established, as well as behavioral
and cognitive (Morris water maze, open field, active avoidance) changes in these mice.