Regulation, cellular localization, and function of the p75 neurotrophin receptor (p75NTR) during the regeneration of facial motoneurons

• Published in: Molecular and cellular neuroscience Vol. 24; no. 2; pp. 307 - 322
• Main Authors: Gschwendtner, Andreas, Liu, ZhiQiang, Hucho, Tim, Bohatschek, Marion, Kalla, Roger, Dechant, Georg, Raivich, Gennadij
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2003
• Subjects: Animals; Facial Nerve - chemistry; Facial Nerve - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Neurons - chemistry; Motor Neurons - physiology; Nerve Regeneration - genetics; Nerve Regeneration - physiology; Rats; Receptor, Nerve Growth Factor; Receptors, Nerve Growth Factor - analysis; Receptors, Nerve Growth Factor - deficiency; Receptors, Nerve Growth Factor - genetics; Receptors, Nerve Growth Factor - physiology
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/S1044-7431(03)00167-2

The common neurotrophin receptor (p75NTR) is a member of the tumor necrosis factor receptor superfamily and binds the neurotrophins nerve growth factor, brain derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. P75NTR is expressed on developing motoneurons and is reexpressed on adult motoneurons under pathological conditions such as nerve trauma or neurodegeneration. Here we examined the regulation and function of p75NTR during regeneration after peripheral transection of the facial nerve of adult mice. Axotomy led to a strong increase in p75NTR immunoreactivity on the injured and regenerating facial motoneurons and on denervated Schwann cells. Cellular colocalization also revealed p75NTR immunoreactivity on neighboring blood vessels and cells in the injured nerve, but not on activated GFAP+ astrocytes or αMβ2+ microglia and macrophages. To determine the function of this receptor we examined the effects of p75NTR deficiency on neuroglial activation, on the speed of axonal regeneration, and on neuronal survival after facial axotomy in two different transgenic mouse lines carrying targeted insertions exon 4 (p75e4−/−) or exon 3 (p75e3−/−) of the p75NTR gene. In both animal models absence of p75NTR led to a twofold, early increase in the number of CD3+. T-cells and in the microglial immunoreactivity for the α5β1, α6β1, and αMβ2 integrins at day 4 in the facial nucleus and in the crushed facial motor nerve. No changes were observed in the number of reactive GFAP+ astrocytes or on late microglial and lymphocyte responses. The rate of axonal elongation in the crushed facial nerve, as well as neuronal survival, was found to be unaffected. Overall, the current study shows that the p75NTR receptor plays an important regulatory role in early neuroglial and immune activation.