MHC class I upregulation is not sufficient to rescue neonatal alpha motoneurons after peripheral axotomy.
Associated with neuronal death, profound synaptic changes occur in the spinal cord during the apoptotic process triggered after axotomy in neonatal rats. With respect to this, the major histocompatibility complex of class I (MHC class I) has recently emerged as a new mechanism related to synaptic stripping and plasticity. The present study investigated the impact of upregulating MHC class I expression by treatment with beta interferon (beta INF) on motoneuron survival, synaptic plasticity and astrogliosis after neonatal sciatic nerve injury. P2 rats were subjected to unilateral axotomy followed by three days of beta INF treatment. The results were analyzed by counting Nissl stained motoneurons, immunohistochemistry (anti-synaptophysin, MHC class I, GFAP and Iba-1) and transmission electron microscopy. INF treatment induced an increased expression of MHC class I, which resulted in a stronger synaptic elimination process in the spinal cord, as seen by the synaptophysin labeling. GFAP and Iba-1 upregulation were not significantly altered by the INF treatment, displaying the same degree of enhanced reactivity as compared to the placebo group. The ultrastructural analysis showed that, apart from the overall reduction of inputs in the neuropil, no statistical differences were present when comparing the INF and placebo treated animals. Also, neuronal survival was not altered by cytokine administration. The present results provide evidence that MHC class I upregulation after neonatal injury does not change the fate of lesioned motoneurons. In this way, the lack of neurotrophic support may cause broader synaptic loss, which superposes the more subtle effects of the upregulation of MHC class I.
Payés
Ana Carolina Linardi Munguia
AC
Department of Anatomy, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Zanon
Renata Graciele
RG
Pierucci
Amauri
A
Oliveira
Alexandre L R
AL
D000818:Animals; D000831:Animals, Newborn; D019771:Axotomy; D002135:Calcium-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D008840:Microfilament Proteins; D046529:Microscopy, Electron, Transmission; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016708:Synaptophysin / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D015395:Histocompatibility Antigens Class I; D007155:Immunologic Factors; D008840:Microfilament Proteins; D016708:Synaptophysin; D016899:Interferon-beta