PMID- 25669997
OWN - NLM
STAT- MEDLINE
DCOM- 20150407
LR  - 20150211
IS  - 1872-8421 (Electronic)
IS  - 0165-5728 (Linking)
VI  - 279
DP  - 2015 Feb 15
TI  - Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and 
      autism spectrum disorders.
PG  - 33-8
LID - S0165-5728(14)00987-4 [pii]
LID - 10.1016/j.jneuroim.2014.12.003 [doi]
AB  - Rett syndrome is a neurodevelopmental disorder, which occurs in about 1:15,000 
      females and presents with neurologic and communication defects. It is transmitted 
      as an X-linked dominant linked to mutations of the methyl-CpG-binding protein 
      (MeCP2), a gene transcription suppressor, but its definitive pathogenesis is 
      unknown thus hindering development of effective treatments. Almost half of 
      children with Rett syndrome also have behavioral symptoms consistent with those 
      of autism spectrum disorders (ASDs). PubMed was searched (2005-2014) using the 
      terms: allergy, atopy, brain, brain-derived neurotrophic factor (BDNF), 
      corticotropin-releasing hormone (CRH), cytokines, gene mutations, inflammation, 
      mast cells (MCs), microglia, mitochondria, neurotensin (NT), neurotrophins, 
      seizures, stress, and treatment. There are a number of intriguing differences and 
      similarities between Rett syndrome and ASDs. Rett syndrome occurs in females, 
      while ASDs more often in males, and the former has neurologic disabilities unlike 
      ASDs. There is evidence of dysregulated immune system early in life in both 
      conditions. Lack of microglial phagocytosis and decreased levels of BDNF appear 
      to distinguish Rett syndrome from ASDs, in which there is instead microglia 
      activation and/or proliferation and possibly defective BDNF signaling. Moreover, 
      brain mast cell (MC) activation and focal inflammation may be more prominent in 
      ASDs than Rett syndrome. The flavonoid luteolin blocks microglia and MC 
      activation, provides BDNF-like activity, reverses Rett phenotype in mouse models, 
      and has a significant benefit in children with ASDs. Appropriate formulations of 
      luteolin or other natural molecules may be useful in the treatment of Rett 
      syndrome.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Theoharides, Theoharis C
AU  - Theoharides TC
AD  - Molecular Immunopharmacology and Drug Discovery Laboratory, Department of 
      Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 
      Harrison Avenue, Boston, MA, USA; Department of Internal Medicine, Tufts 
      University School of Medicine, 136 Harrison Avenue, Boston, MA, USA; Tufts 
      Medical Center, Boston, MA, USA; Department of Psychiatry, Tufts University 
      School of Medicine, 136 Harrison Avenue, Boston, MA, USA. Electronic address: 
      theoharis.theoharides@tufts.edu.
FAU - Athanassiou, Marianna
AU  - Athanassiou M
AD  - Molecular Immunopharmacology and Drug Discovery Laboratory, Department of 
      Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 
      Harrison Avenue, Boston, MA, USA.
FAU - Panagiotidou, Smaro
AU  - Panagiotidou S
AD  - Molecular Immunopharmacology and Drug Discovery Laboratory, Department of 
      Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 
      Harrison Avenue, Boston, MA, USA.
FAU - Doyle, Robert
AU  - Doyle R
AD  - Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston MA, 
      USA; Harvard Medical School, Boston MA, USA.
LA  - eng
GR  - AR47652/AR/NIAMS NIH HHS/United States
GR  - NS38326/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20141204
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Cytokines)
RN  - 0 (MECP2 protein, human)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (Nerve Growth Factors)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
SB  - IM
MH  - *Brain/immunology/metabolism
MH  - Child Development Disorders, Pervasive/genetics/*pathology
MH  - Corticotropin-Releasing Hormone
MH  - Cytokines
MH  - Female
MH  - Humans
MH  - Male
MH  - Methyl-CpG-Binding Protein 2/genetics
MH  - Mutation/genetics
MH  - Nerve Growth Factors/*metabolism
MH  - PubMed/statistics & numerical data
MH  - Rett Syndrome/genetics/*pathology
MH  - Signal Transduction/*physiology
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Inflammation
OT  - Mast cells
OT  - Microglia
OT  - Mitochondria
OT  - Rett syndrome
OT  - Treatment
EDAT- 2015/02/12 06:00
MHDA- 2015/04/08 06:00
CRDT- 2015/02/12 06:00
PHST- 2014/08/09 00:00 [received]
PHST- 2014/11/18 00:00 [revised]
PHST- 2014/12/02 00:00 [accepted]
PHST- 2015/02/12 06:00 [entrez]
PHST- 2015/02/12 06:00 [pubmed]
PHST- 2015/04/08 06:00 [medline]
AID - S0165-5728(14)00987-4 [pii]
AID - 10.1016/j.jneuroim.2014.12.003 [doi]
PST - ppublish
SO  - J Neuroimmunol. 2015 Feb 15;279:33-8. doi: 10.1016/j.jneuroim.2014.12.003. Epub 
      2014 Dec 4.