News Blog readers may have seen previous posts on synaptic pruning. Synaptic pruning involves the elimination of synapses with weak connections between brain neurons. Pruning is especially exuberant after periods of rapid neuronal multiplication (in mid-gestation, around the age of two years, and in late adolescence). Over-exuberant synaptic pruning is associated with schizophrenia. It may also play a crucial role in degenerative brain diseases, such as Alzheimer’s, and in people with memory loss after West Nile fever. The biochemical trigger arises from products of the complement cascade. Astrocytes induce neuronal cells to make the protein C1q, which triggers the complement cascade in neurons. Complement factors, such as C3 attach to weak synapses, and micro-glia (the macrophages of the brain) then ingest the tagged synapses. This process can be visualised by staining living brain cells – bits of synapse end up in the micro-glia. A genetic predisposition to over-express certain complement components increases the risk of schizophrenia markedly, as reported in a previous post. As brains age C1q levels increase four-fold, and this likely predisposes to degenerative diseases, such as Alzheimer’s. Drugs to dampen down this cascade are entering clinical trials. For a lively account if the human story behind one of the leading scientists involved in unravelling this story, see an article by Emily Underwood.
— Richard Lilford, CLAHRC WM Director
- Lilford RJ. Psychiatry Comes of Age. NIHR CLAHRC West Midlands. 11 March 2016.
- Lilford RJ. Molecular Diagnostic Testing, Including Whole-Exome Sequencing, in Children with Autism Spectrum Disorder. NIHR CLAHRC West Midlands. 23 October 2015.
- Underwood E. This woman may know a secret to saving the brain’s synapses. Aug 18 2016.