Damage to the brain gray matter plays an important role in the progression of multiple sclerosis. This study now shows that such damage can be caused by inflammatory reactions that lead to loss of synapses, which impairs neural activity.
Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, in which nerve cells are attacked by the patient's own immune system. In many cases, the disease develops into a progressive form, which is characterized by a shift of pathology from the white matter to the gray matter, for instance to the cerebral cortex. This phase of the disease has so far been difficult to treat and its underlying causes are poorly understood.
Now, a research team has shown in a mouse model that inflammation of the gray matter leads to a decrease in nerve-cell activity, owing to the (potentially reversible) destruction of synapses. "Targeted inhibition of specific types of immune cells can slow synapse damage down, and offers an interesting new therapeutic approach," the senior author explains.
Loss of synapses - the structures that serve as functional contacts between nerve cells - is an early indicator of damage to the cerebral cortex in cases of progressive MS. The researchers therefore suspected that the synapses are the key to the neuronal damage that ensues in this stage of the disease. With the aid of various imaging techniques, the team was able to demonstrate that such widespread loss of synapses can be reproduced in a mouse model of MS. Moreover, their observations revealed that synaptic spines are destroyed by a specific type of immune cells. "These immune cells preferentially eliminate spines, which contain high levels of calcium. We assume that the inflammation reaction itself triggers an influx of calcium, which destabilizes the spines," says the author. "These changes in late-stage MS are reminiscent of those that can also be observed during the early phases of neurodegeneration," the author adds.
The activated immune cells primarily attack excitatory synapses, which are responsible for activating other nerve cells. As a consequence, the level of activity in neural networks decreases. "The nerve cells are effectively silenced," says the senior author. "However, much to our surprise, we discovered that this process is reversible in our model."
As soon as the inflammation is resolved, the normal number of synapses is restored and the neurons once again exhibit their normal patterns of activity. These results contrast with findings in patients with progressive MS, in whom the cerebral cortex is permanently damaged. "Presumably, the mechanisms responsible for recovery cannot come into effect in these patients, because the inflammation is chronic and remains unresolved," says neuropathologist. "In our model, we induced an acute inflammatory reaction, which is resolved within a few days."
New pharmaceutical agents might be able to specifically inhibit the activation of the immune cells responsible for synapse destruction and could therefore slow the progress of the disease. However, it is crucial that such inhibitors do not completely block the action of these cells, so that they can continue to carry out their essential functions. The authors of the study hope that this concept can help develop therapeutic approaches that will effectively curb the progression of MS.
https://www.en.uni-muenchen.de/news/newsarchiv/2021/kerschensteiner_synapses.html
https://www.nature.com/articles/s41593-020-00780-7
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Flocalized-calcium&filter=22
Calcium accumulation activates immune cells to remove synapses in inflammation
- 1,021 views
- Added
Edited
Latest News
TB blood test which could d…
By newseditor
Posted 27 Mar
Propionate supplementation…
By newseditor
Posted 27 Mar
Role of human Kallistatin i…
By newseditor
Posted 26 Mar
Addressing both flu and COV…
By newseditor
Posted 26 Mar
How the brain senses body p…
By newseditor
Posted 26 Mar
Other Top Stories
Attention recruits frontal cortex in human infants
Read more
Early life stress in neurons is mediated by epigenetic mechanism
Read more
Negative mood linked to prolonged amygdala activity
Read more
How the brain understands sentences
Read more
Does 'harsh parenting' lead to smaller brains?
Read more
Protocols
All-optical presynaptic pla…
By newseditor
Posted 23 Mar
Epigenomic tomography for p…
By newseditor
Posted 20 Mar
A mouse DRG genetic toolkit…
By newseditor
Posted 17 Mar
An optogenetic method for t…
By newseditor
Posted 13 Mar
Profiling native pulmonary…
By newseditor
Posted 08 Mar
Publications
Balancing neuronal activity…
By newseditor
Posted 28 Mar
OSBP-mediated PI(4)P-choles…
By newseditor
Posted 28 Mar
Integrated plasma proteomic…
By newseditor
Posted 27 Mar
APP antisense oligonucleoti…
By newseditor
Posted 27 Mar
Targeting Erbin-mitochondri…
By newseditor
Posted 27 Mar
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar