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- Berg, A., et al.
(författare)
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Reduced removal of synaptic terminals from axotomized spinal motoneurons in the absence of complement C3
- 2012
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 237:1, s. 8-17
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Tidskriftsartikel (refereegranskat)abstract
- Complement proteins C1q and C3 play a critical role in synaptic elimination during development. Axotomy of spinal motoneurons triggers removal of synaptic terminals from the cell surface of motoneurons by largely unknown mechanisms. We therefore hypothesized that the complement system is involved also in synaptic stripping of injured motoneurons. In the sciatic motor pool of wild type (WT) mice, the immunoreactivity (IR) for both C1q and C3 was increased after sciatic nerve transection (SNT). Mice deficient in C3 (C3(-/-)) showed a reduced loss of synaptic terminals from injured motoneurons at one week after SNT, as assessed by immunoreactivity for synaptic markers and electron microscopy. In particular, the removal of putative inhibitory terminals, immunopositive for vesicular inhibitory amino acid transporter (VIAAT) and ultrastructurally identified as type F synapses, was reduced in C3(-/-) mice. In contrast, lesion-induced removal of nerve terminals in C1q(-/-) mice appeared similar to WT mice. Growth associated protein (GAP)-43 mRNA expression in lesioned motoneurons increased much more in C3(-/-) compared to WT mice after SNT. After sciatic nerve crush (SNC), the C3(-/-) mice showed a faster functional recovery, assessed as grip strength, compared to WT mice. No differences were detected regarding nerve inflammation at the site of injury or pattern of muscle reinnervation. These data indicate that a non-classical pathway of complement activation is involved in axotomy-induced adult synapse removal, and that its inhibition promotes functional recovery. (c) 2012 Elsevier Inc. All rights reserved.
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| 2. |
- Cullheim, S, et al.
(författare)
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Classic major histocompatibility complex class I molecules: new actors at the neuromuscular junction
- 2010
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Ingår i: The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry. - : SAGE Publications. - 1089-4098. ; 16:6, s. 600-607
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Tidskriftsartikel (refereegranskat)abstract
- The presence and function of immune molecules in the central nervous system (CNS) have been under debate for a long time. There is mounting evidence that molecules fundamental for immune function are indeed expressed by both neurons and glia and that such molecules may have important nonimmunological function for the organization and stability of synaptic connections. Here, we present data showing that the classic form of major histocompatibility complex (MHC) class I molecules is expressed in spinal motoneurons, in particular in their axons and presynaptically at their synapses with skeletal muscles, the neuromuscular junctions (NMJs). The expression is strongly increased after axon lesion in the peripheral nerve. In the absence of classic MHC I, the organization of NMJs is disturbed with NMJs in higher numbers than normal, thereby equipping single muscle fibers with multiple NMJs. It is suggested that these effects are mediated by the classic MHC class I in the motor axons, possibly through effects mediated by the peripherally myelinating Schwann cells, which express receptors for classic MHC class I. The presence of immune molecules normally used by other cells for antigen presentation in peripheral motor axons may have implications for the onset of specific motoneuron disease.
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