PMID- 27263037
OWN - NLM
STAT- MEDLINE
DCOM- 20180130
LR  - 20211204
IS  - 1433-8491 (Electronic)
IS  - 0940-1334 (Linking)
VI  - 267
IP  - 5
DP  - 2017 Aug
TI  - mTOR inhibitor reverses autistic-like social deficit behaviours in adult rats 
      with both Tsc2 haploinsufficiency and developmental status epilepticus.
PG  - 455-463
LID - 10.1007/s00406-016-0703-8 [doi]
AB  - Epilepsy is a major risk factor for autism spectrum disorder (ASD) and 
      complicates clinical manifestations and management of ASD significantly. Tuberous 
      sclerosis complex (TSC), caused by TSC1 or TSC2 mutations, is one of the medical 
      conditions most commonly associated with ASD and has become an important model to 
      examine molecular pathways associated with ASD. Previous research showed reversal 
      of autism-like social deficits in Tsc1 (+/-) and Tsc2 (+/-) mouse models by 
      mammalian target of rapamycin (mTOR) inhibitors. However, at least 70 % of 
      individuals with TSC also have epilepsy, known to complicate the severity and 
      treatment responsiveness of the behavioural phenotype. No previous study has 
      examined the impact of seizures on neurocognitive reversal by mTOR inhibitors. 
      Adult Tsc2 (+/-) (Eker)-rats express social deficits similar to Tsc2 (+/-) mice, 
      with additive social deficits from developmental status epilepticus (DSE). DSE 
      was induced by intraperitoneal injection with kainic acid at post-natal days P7 
      and P14 (n = 12). The experimental group that modelled TSC pathology carried the 
      Tsc2 (+/-) (Eker)-mutation and was challenged with DSE. The wild-type controls 
      had not received DSE (n = 10). Four-month-old animals were analysed for social 
      behaviour (T1), then treated three times during 1 week with 1 mg/kg everolimus 
      and finally retested in the post-treatment behavioural analysis (T2). In the 
      experimental group, both social interaction and social cognition were impaired at 
      T1. After treatment at T2, behaviour in the experimental group was 
      indistinguishable from controls. The mTOR inhibitor, everolimus, reversed social 
      deficit behaviours in the Tsc2 haploinsufficiency plus DSE animal model to 
      control levels.
FAU - Schneider, Miriam
AU  - Schneider M
AD  - Research Group Developmental Neuropsychopharmacology, Institute of 
      Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, 
      University of Heidelberg, Mannheim, Germany.
FAU - de Vries, Petrus J
AU  - de Vries PJ
AD  - Division of Child and Adolescent Psychiatry, University of Cape Town, Cape Town, 
      South Africa.
FAU - Schonig, Kai
AU  - Schonig K
AD  - Department of Molecular Biology, Central Institute of Mental Health, Medical 
      Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
FAU - Rossner, Veit
AU  - Rossner V
AD  - Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav 
      Carus, Faculty of Medicine, Technical University of Dresden, Dresden, Germany.
FAU - Waltereit, Robert
AU  - Waltereit R
AUID- ORCID: 0000-0002-5338-2765
AD  - Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav 
      Carus, Faculty of Medicine, Technical University of Dresden, Dresden, Germany. 
      robert.waltereit@uniklinikum-dresden.de.
AD  - Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, 
      Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. 
      robert.waltereit@uniklinikum-dresden.de.
LA  - eng
PT  - Journal Article
DEP - 20160604
PL  - Germany
TA  - Eur Arch Psychiatry Clin Neurosci
JT  - European archives of psychiatry and clinical neuroscience
JID - 9103030
RN  - 0 (Tsc2 protein, mouse)
RN  - 0 (Tsc2 protein, rat)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Autism Spectrum Disorder/*complications/*genetics
MH  - Body Weight/genetics
MH  - Disease Models, Animal
MH  - Everolimus/*therapeutic use
MH  - Haploinsufficiency/genetics
MH  - Interpersonal Relations
MH  - Locomotion/drug effects/genetics
MH  - Rats
MH  - Rats, Transgenic
MH  - Recognition, Psychology/drug effects/physiology
MH  - Social Behavior Disorders/*drug therapy/*etiology
MH  - Status Epilepticus/*complications
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/*deficiency/genetics
OTO - NOTNLM
OT  - Animal model
OT  - Autism spectrum disorder
OT  - Everolimus
OT  - Experimental therapy
OT  - Social cognition
OT  - Tuberous sclerosis complex
EDAT- 2016/06/06 06:00
MHDA- 2018/01/31 06:00
CRDT- 2016/06/06 06:00
PHST- 2016/02/25 00:00 [received]
PHST- 2016/05/23 00:00 [accepted]
PHST- 2016/06/06 06:00 [pubmed]
PHST- 2018/01/31 06:00 [medline]
PHST- 2016/06/06 06:00 [entrez]
AID - 10.1007/s00406-016-0703-8 [pii]
AID - 10.1007/s00406-016-0703-8 [doi]
PST - ppublish
SO  - Eur Arch Psychiatry Clin Neurosci. 2017 Aug;267(5):455-463. doi: 
      10.1007/s00406-016-0703-8. Epub 2016 Jun 4.