PMID- 35782388
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 15
DP  - 2022
TI  - mTOR-Dependent Spine Dynamics in Autism.
PG  - 877609
LID - 10.3389/fnmol.2022.877609 [doi]
LID - 877609
AB  - Autism Spectrum Conditions (ASC) are a group of neurodevelopmental disorders 
      characterized by deficits in social communication and interaction as well as 
      repetitive behaviors and restricted range of interests. ASC are complex genetic 
      disorders with moderate to high heritability, and associated with atypical 
      patterns of neural connectivity. Many of the genes implicated in ASC are involved 
      in dendritic spine pruning and spine development, both of which can be mediated 
      by the mammalian target of rapamycin (mTOR) signaling pathway. Consistent with 
      this idea, human postmortem studies have shown increased spine density in ASC 
      compared to controls suggesting that the balance between autophagy and 
      spinogenesis is altered in ASC. However, murine models of ASC have shown 
      inconsistent results for spine morphology, which may underlie functional 
      connectivity. This review seeks to establish the relevance of changes in 
      dendritic spines in ASC using data gathered from rodent models. Using a 
      literature survey, we identify 20 genes that are linked to dendritic spine 
      pruning or development in rodents that are also strongly implicated in ASC in 
      humans. Furthermore, we show that all 20 genes are linked to the mTOR pathway and 
      propose that the mTOR pathway regulating spine dynamics is a potential mechanism 
      underlying the ASC signaling pathway in ASC. We show here that the direction of 
      change in spine density was mostly correlated to the upstream positive or 
      negative regulation of the mTOR pathway and most rodent models of mutant mTOR 
      regulators show increases in immature spines, based on morphological analyses. We 
      further explore the idea that these mutations in these genes result in aberrant 
      social behavior in rodent models that is due to these altered spine dynamics. 
      This review should therefore pave the way for further research on the specific 
      genes outlined, their effect on spine morphology or density with an emphasis on 
      understanding the functional role of these changes in ASC.
CI  - Copyright (c) 2022 Chaudry and Vasudevan.
FAU - Chaudry, Shabani
AU  - Chaudry S
AD  - School of Biological Sciences, University of Reading, Reading, United Kingdom.
FAU - Vasudevan, Nandini
AU  - Vasudevan N
AD  - School of Biological Sciences, University of Reading, Reading, United Kingdom.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220615
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC9241970
OTO - NOTNLM
OT  - autism spectrum conditions
OT  - autophagy
OT  - mTORC1
OT  - neurocircuitry
OT  - rodent models
OT  - social behaviors
OT  - spine density
OT  - synaptic transmission
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/07/06 06:00
MHDA- 2022/07/06 06:01
PMCR- 2022/01/01
CRDT- 2022/07/05 09:50
PHST- 2022/02/16 00:00 [received]
PHST- 2022/04/25 00:00 [accepted]
PHST- 2022/07/05 09:50 [entrez]
PHST- 2022/07/06 06:00 [pubmed]
PHST- 2022/07/06 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2022.877609 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2022 Jun 15;15:877609. doi: 10.3389/fnmol.2022.877609. 
      eCollection 2022.