Another Example of Immune System Getting Involved in Development - Neurodegenerative diseases may be regarded as autoimmune diseases

In addition to my last post in November, 2007, Beth Stevens et al. published a paper on Cell that adds another example of immune system involved in development, also in central nervous system (CNS).

Inspired by the coincidence of dynamic synaptic refinement with appearance of astrocytes in the postnatal brain, and recent evidence indicating a role for astrocyte-derived signals in synapse development, the authors used gene profiling approach to screen candidate retinal ganglion cells (RGCs) genes that are upregulated by astrocytes. RT-PCR confirmed this finding. And further histology studies also verified that C1q is localized to developing CNS synapse in vivo throughout inner plexiform layer (IPL), retinal ganglion cells (RGCs), distal lateral geniculate nucleus (dLGNs). C1q "tag" unwanted CNS synapses as they opsonize pathogen or antibody, pruning of inappropriate synapses. Further, C1q-deficient (C1qKO) mice have defects in this developement shift of synaptic convergence. Without synapse elimination, LGN neurons remain multiply innervated by RGC axons, and they are defective in eye-specific segregation.

On the other hand, they also revealed that the expression of C1q declines as the nervous system mature. These neuronal C1q are downregulated in adult. However, they "revive" again in a mouse model of glaucoma! Their observation showed that C1q overexpress at early stage of glaucoma, prior to overt neurodegeneration.

This paper underscores the role that the immune system may act against "self" in a normal, physiological way in development. Moreover, it highlights hazardous effect when this immune response went too far, shedding a light on that neurodegenerative diseases may be taken as autoimmune diseases. There are quite a lot questions to be asked. In terms of neurology and neurosciene, can this model be broadened from retina and geniculate nucleus to cortex, midbrain or other part of CNS? Are C1q and complement cascade the mechanism how we forget, and how we reshape our memory? Are they also involved in other neurodegenerative disease, say Alzheimer or Parkinsonism? In terms of rheumatology and immunology, are there any other members of immune system participating in this process other than complement system? Although it has been known that steroid can cause glaucoma, but could we treat it, and other neurodegenerative diseases, from the perspective of autoimmune diseases?

Wilfred Wu Wonderland [ Portal | 1996 edition | 2001 edition | 2006 Blog ]
Tags: Medicine, Medical Science, Biomedical Science, Biological Science, Bioscience, Medicine-Immunology, Medicine-Rheumatology, Medicine-Neurology, Medicine-Neuroscience, Medicine-Developmental Biology, CNS, Central Nervous System, Medicine-Developmental Biology-Synapse Convergence, Synapse refinement, Synapse elimination, Astrocyte, Medicine-Rheumatology-Autoimmune disease, Medicine-Neurology-Neurodegenerative Disease, Medicine-Immunology-Complement Cascade, C1q, C1qA, C1qB, C1qC, Astrocyte, Glia cells, RGC, RGCs, Retinal ganglion cells, gene profiling, RT-PCR, IPL, inner plexiform layer, LGN, LGNs, Lateral geneiculate nucleus, Medicine-Ophthalmology-Glaucoma, Medicine-Ophthalmmology, Cortex, Midbrain, Memory, Alzheimer, Parkinsonism, Glucocorticoid, Steroid