Involvement of MHC I, TLR2 and TLR4 in the synaptic plasticity and functional reovery following crushing of spinal ventral roots in mice

• Grant number: 19/02714-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2019
• End date: July 31, 2023
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Luciana Politti Cartarozzi
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 18/05006-0 - Sensorimotor recovery following spinal root axotomy: use of different experimental approaches, AP.TEM

Abstract

Peripheral nerve lesions are followed by an increase in expression of immune molecules, such as the Major Histocompatibility Complex Class I (MHC-I). The MHC-I upregulation is directly related to the synaptic plasticity process, glial cell activity modulation and functional recovery. Knockout mice for the MHC-I obligatory chain ²2 microglobulin (²2m), show increased reduction in synaptic density and deficit in axonal regeneration after peripheral lesion. There are other receptors that share MHC-I domains, such as paired-immunoglobulin receptors (PIR-A and B) and Killer-cell immunoglobulin-like receptors (KIR), specifically KIR3DL2. Such receptors have an inhibitory role in axonal growth after lesion. In the same way, Toll-like receptors 2 and 4 (TLR 2 and TLR 4) are activated in the spinal cord after lesion, relating TLR 4 to mediate synaptic stability and TLR 2, synaptic elimination. The present project aims to evaluate the synaptic plasticity process and functional recovery after ventral root crush (VRC) in knockout mice for ²2m, TLR 4 and TLR 2, correlating morphological findings with glial reactivity and expression of proteins related to the signaling pathways involving immune system components.

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)

PEREZ, MATHEUS; CARTAROZZI, LUCIANA POLITTI; CHIAROTTO, GABRIELA BORTOLANCA; GUIMARAES, FRANCISCO SILVEIRA; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Short and long-term neuroprotective effects of cannabidiol after neonatal peripheral nerve axotomy. Neuropharmacology, v. 197, OCT 1 2021. (12/22751-5, 18/05006-0, 19/02714-7)

CARTAROZZI, LUCIANA POLITTI; PEREZ, MATHEUS; FERNANDES, GABRIEL GRIPP; CHIAROTTO, GABRIELA BORTOLANCA; LUZO, ANGELA CRISTINA MALGEIROS; CAMPOS, ALLINE CRISTINA; KIRCHHOFF, FRANK; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. europrotection and gliosis attenuation by intravenous application of human mesenchymal stem cells (hMSC) following ventral root crush in mic. Molecular and Cellular Neuroscience, v. 118, JAN 2022. (18/05006-0, 19/02714-7)

HOELZ, AMANDA GARCIA; BERNARDES, DANIELLE; CARTAROZZI, LUCIANA POLITTI; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Gliosis attenuation in experimental autoimmune encephalomyelitis by a combination of dimethyl fumarate and pregabalin. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 16, p. 11-pg., 2022-08-12. (18/05006-0, 15/04665-2, 14/06892-3, 19/02714-7)