The synaptic pruning of newborn neurons by microglia depends upon phosphatidylserine in the adult brain. This mechanism is essential for the maturation of newborn neurons.
A research group led by Kazunobu Sawamoto, a teacher at Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences and National Institute for Physiological Sciences, and Chihiro Kurematsu, a fourth-year trainee at Nagoya City University School of Medicine, has actually clarified the system that manages synaptic pruning of new neurons in the adult brain.
As these brand-new nerve cells grow, they form connections called synapses with existing nerve cells to develop functional neural circuits. It was unidentified how new neurons in the adult brain remove additional synapses throughout maturation.
Three-dimensional restoration of electron microscopic images showing a synaptic spinal column (blue) of a new nerve cell (pink), which forms a synapse with another nerve cell (light blue), engulfed by microglia (green) in the adult mouse olfactory bulb. These results suggest that the synaptic pruning of newborn neurons by microglia is PS-dependent in the adult brain, and that this system is important for the right maturation of newborn neurons.
In the mammalian brain, neural stem cells exist even after birth, and brand-new nerve cells are produced. As these new neurons grow, they form connections called synapses with existing nerve cells to develop functional neural circuits. For the brain to develop and function usually, it is essential to preserve a suitable variety of synapses, but the mechanism to control the variety of synapses has not been completely understood. Cells called microglia, which exist near afferent neuron, play an essential function in this process. Microglia can “consume” (phagocytose) dead cells and are also known to digest extra synapses during development. It was unidentified how brand-new nerve cells in the adult brain remove additional synapses during maturation.
Three-dimensional restoration of electron microscopic images revealing a synaptic spine (blue) of a brand-new neuron (pink), which forms a synapse with another nerve cell (light blue), engulfed by microglia (green) in the adult mouse olfactory bulb. Credit: © 2022 Kurematsu et al. Initially published in Journal of Experimental Medicine
Sawamotos group focused on phosphatidylserine (PS), a molecule that typically lives inside the cell membrane, however is found on the external surface of dead cells or establishing synapses, where it is acknowledged by microglia. Initially, the researchers used an electron microscopic lense to take a look at the microglia in information and observed that microglia really engulf synapses. Next, they took a look at the localization of PS and found that PS is exposed outside the cell membrane at synapses in the adult mouse brain, especially at less active synapses.
” To study whether microglial PS detection is very important for synaptic pruning and typical nerve cell maturation in the adult brain, we needed to see what takes place when PS is masked in living adult mice,” Sawamoto stated.
Nerve cells in these mice showed electrophysiological abnormalities. These results show that the synaptic pruning of newborn neurons by microglia is PS-dependent in the adult brain, and that this system is crucial for the appropriate maturation of newborn neurons.
Current research studies have actually revealed that brand-new neurons are also produced in the human brain throughout the neonatal duration, and microglial synaptic pruning is thought to be essential for postnatal brain advancement.
” We hope that investigating PS-dependent synaptic elimination in mouse designs of brain illness will cause the advancement of brand-new restorative methods for human pathological conditions such as autism, where irregularities in microglia and synaptic density have been observed,” said Kurematsu.
The complete findings of the study are published in the Journal of Experimental Medicine.
Recommendation: “Phosphatidylserine-dependent synaptic pruning by microglia in the maturation of adult-born neurons” by Chihiro Kurematsu, Masato Sawada, Masaki Ohmuraya, Motoki Tanaka, Kazuya Kuboyama, Takashi Ogino, Mami Matsumoto, Hisashi Oishi, Hiroyuki Inada, Yuri Ishido, Yukina Sakakibara, Huy Bang Nguyen, Truc Quynh Thai, Shinichi Kohsaka, Nobuhiko Ohno, Maki K. Yamada, Masato Asai, Masahiro Sokabe, Junichi Nabekura, Kenichi Asano, Masato Tanaka and Kazunobu Sawamoto, 17 March 2022, Journal of Experimental Medicine.DOI: 10.1084/ jem.20202304.
In addition to Kazunobu Sawamoto and Chihiro Kurematsu, co-authors of this research study article include scientists from Nagoya City University, National Institute for Physiological Sciences, Hyogo College of Medicine, Aichi Developmental Disability Center, University of Medicine and Pharmacy of Ho Chi Minh City, Pham Ngoc Thach University of Medicine, National Institute of Neuroscience, Jichi Medical University, Tokushima Bunri University, Nagoya University, and Tokyo University of Pharmacy and Life Sciences.
