Opposite effects of Toll-like receptors 2 and 4 on synaptic stability in the spinal cord after peripheral nerve injury

• Grant number: 12/19612-3
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Duration: November 01, 2012 - April 30, 2013
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Background: Glial cells are involved in the synaptic elimination process that follows neuronal lesions. They are also responsible for mediating the interaction between the nervous and immune systems. Neurons and glial cells express Toll-like receptors (TLRs), which may affect central nervous system (CNS) plasticity. Because TLRs might also have non-immune functions in the spinal cord injury (SCI), the present work aimed to investigate the influence of TLR2 and TLR4 on synaptic plasticity and glial reactivity after peripheral nerve axotomy. Methods: The lumbar spinal cords of C3H/HePas wild-type mice (WT), C3H/HeJ TLR4-mutant mice, C57BL/6J WT mice, and C57BL/6J TLR2-knockout mice were studied after unilateral sciatic nerve transection. The mice were euthanized via intracardiac perfusion, and the spinal cord was processed for immunohistochemistry, transmission electron microscopy (TEM), Western blotting, cell culture, and RT-PCR. Primary cultures of astrocytes from newborn mice were established to study the astrocyte response in the absence of TLR2 and the deficiency of TLR4 expression.Results: The results showed that TLR4 and TLR2 expression in the CNS may have opposite effects on the stability of presynaptic terminals in the spinal cord. In one hand, TLR4 contributes to synaptic preservation of terminals in apposition to lesioned motoneurons after peripheral injury, regardless the major histocompatibility complex of class I (MHC I) expression. Also, in the presence of TLR4, there is upregulation of GDNF and downregulation of IL6, but no morphological differences in glial reactivity can be observed. On the contrary, TLR2 expression leads to greater synaptic loss, correlating with increased astrogliosis and up-regulation of pro-inflammatory interleukins. Moreover, the absence of TLR2 resulted in the upregulation of neurotrophic factors and MHC I expression.Conclusion: TLR4 and TLR2 in the CNS may have opposite effects on the stability of presynaptic terminals in the spinal cord as well as in astroglial reaction, indicating possible roles for these proteins in neuronal and glial responses to injury. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FRERIA, CAMILA MARQUES; VELLOSO, LICIO AUGUSTO; OLIVEIRA, ALEXANDRE L. R.. Opposing effects of Toll-like receptors 2 and 4 on synaptic stability in the spinal cord after peripheral nerve injury. JOURNAL OF NEUROINFLAMMATION, v. 9, OCT 23 2012. (12/19612-3, 10/17688-7)