The poor function of microglia, the brain’s immune cells in individuals exposed to early life adversity (ELA) promotes aberrant responses to stress in adulthood that may be linked to mental illness, according to a new study.
During brain development, microglia prune unnecessary synapses resulting in the formation of refined, functional circuits. Disruption of that process leaves too many synapses, changing the behavioral and hormonal responses to further stresses later in life.
The study was published online today in Cell Reports.
“Much of neuroscience and study of brain diseases has focused on the brain’s neurons. This study highlights that in addition to neurons, other brain cells, and especially immune cells, play crucial roles in brain health and disease,” said the senior author.
Brain development is governed by both genetics and early life experiences. Several mental illnesses, characterized by aberrant reactions to stress, often arise after ELA but its effect on stress-related brain circuit maturation was unclear. In the study, transgenic mice of both sexes were housed in temperature-controlled, quiet, uncrowded conditions on a schedule of 12 hours of light and 12 hours of dark, with free access to food and water. The control dams were place in cages with standard amounts of corn husk bedding and nesting material. The ELA dams received only one-half nestlet and reduced bedding materials.
Researchers found that ELA increased functional excitatory synapses onto stress-sensitive hypothalamic corticotropin-releasing hormone-(CRH) expressing neurons, resulting from disrupted developmental synapse pruning by adjacent microglia in the mouse pups. These neuroimmune interactions during development thus made the CRH cells, and they mice, more vulnerability to stress.
“Our discoveries reveal that ELA leads to reduced microglial process dynamics during a sensitive period. We know this is a direct effect of ELA, because we artificially activated microglia in stressed neonatal mice, which prevented the synapse excess and the abnormal responses to stress during adulthood,” the author said. “The next steps are to identify if the molecules that lead to microglial dysfunction can be used to prevent their malfunction and the resulting vulnerability to stress. This may be translatable to people.”
https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00348-5
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fearly-stress-induced&filter=22
Early stress-induces impaired microglial pruning of excitatory synapses
- 1,248 views
- Added
Latest News
Protein that helps COVID-19…
By newseditor
Posted 26 Jul
Spinal Muscular Atrophy (SM…
By newseditor
Posted 26 Jul
Link between bowel movement…
By newseditor
Posted 26 Jul
Inhibition of IL-11 signall…
By newseditor
Posted 25 Jul
Brain changes linked to obe…
By newseditor
Posted 25 Jul
Other Top Stories
Deep-sleep brain waves predict blood sugar control
Read more
Extracellular cytochrome nanowires appear to be ubiquitous in microbes
Read more
Distinct connectivity patterns for depression associated with traum…
Read more
Antisense therapy restores fragile X protein production in human cells
Read more
Biomarker for allergic reaction in kidneys identified!
Read more
Protocols
A systems biology approach…
By newseditor
Posted 24 Jul
quantms: a cloud-based pipe…
By newseditor
Posted 22 Jul
Emerging tools and best pra…
By newseditor
Posted 19 Jul
Directly selecting cell-typ…
By newseditor
Posted 17 Jul
PUFFFIN: an ultra-bright, c…
By newseditor
Posted 16 Jul
Publications
Hepatocyte-intrinsic SMN de…
By newseditor
Posted 26 Jul
Aberrant bowel movement fre…
By newseditor
Posted 26 Jul
A pseudoautosomal glycosyla…
By newseditor
Posted 26 Jul
Microglia protect against a…
By newseditor
Posted 26 Jul
Rigor and reproducibility i…
By newseditor
Posted 26 Jul
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
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
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