Constitutive nuclear factor-kappa B activity is required for central neuron survival.

The function of nuclear factor (NF)-kappaB within the developing and mature CNS is controversial. We have generated transgenic mice to reveal NF-kappaB transcriptional activity in vivo. As expected, constitutive NF-kappaB activity was observed within immune organs, and tumor necrosis factor-inducible NF-kappaB activity was present in mesenchymal cells.

NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis.

The mechanisms employed by the p75 neurotrophin receptor (p75NTR) to mediate neurotrophin-dependent apoptosis are poorly defined. Two-hybrid analyses were used to identify proteins involved in p75NTR apoptotic signaling, and a p75NTR binding partner termed NRAGE (for neurotrophin receptor-interacting MAGE homolog) was identified. NRAGE binds p75NTR in vitro and in vivo, and NRAGE associates with the plasma membrane when NGF is bound to p75NTR.

The p75 neurotrophin receptor (p75NTR) alters tumor necrosis factor-mediated NF-kappaB activity under physiological conditions, but direct p75NTR-mediated NF-kappaB activation requires cell stress.

The p75 neurotrophin receptor (p75NTR) has been linked to activation of the NF-kappaB transcriptional complex in oligodendrocytes, Schwann cells, and PCNA cells. In this report, tumor necrosis factor (TNF)- and neurotrophin-mediated NF (nuclear factor)-kappaB activation were compared in several cell lines. All cell types showed TNF-mediated activation of NF-kappaB, but direct neurotrophin-dependent activation of NF-kappaB was never observed under normal growth conditions.

Transgenic mice expressing the intracellular domain of the p75 neurotrophin receptor undergo neuronal apoptosis.

We have asked whether p75(NTR) may play a role in neuronal apoptosis by producing transgenic mice that express the p75(NTR) intracellular domain within peripheral and central neurons. These animals showed profound reductions in numbers of sympathetic and peripheral sensory neurons as well as cell loss in the neocortex, where there is normally little or no p75(NTR) expression. Developmental loss of facial motor neurons was not observed, but induced expression of the p75(NTR) intracellular domain within adult animals led to increased motor neuron death after axotomy.

Quantitative measurement from vascular casts.

A review of quantitative measurements show casting materials shrink from 0.2 - 20% and have viscosities ranging from 1.4 - 100,000 centipoise.