PMID- 29883228
OWN - NLM
STAT- MEDLINE
DCOM- 20200714
LR  - 20211204
IS  - 1563-5279 (Electronic)
IS  - 0020-7454 (Linking)
VI  - 130
IP  - 1
DP  - 2020 Jan
TI  - Effectiveness of low dose of rapamycin in preventing seizure-induced anxiety-like 
      behaviour, cognitive impairment, and defects in neurogenesis in developing rats.
PG  - 9-18
LID - 10.1080/00207454.2018.1486827 [doi]
AB  - Aims: Previous studies have demonstrated that rapamycin prevents seizure-induced 
      anxiety-like behaviors. However, rapamycin had been used at a higher dose of 3 
      mg/kg and resulted in side effects in immature animals. This work was designed to 
      explore whether a lower dose of rapamycin has similar efficacy but has milder 
      side effects.Methods: Acute seizures were induced by injection of pilocarpine at 
      postnatal 10-day Sprague-Dawley rats. Western blot analysis was used to detect 
      changes in mammalian target of rapamycin (mTOR) pathway after seizure. 
      Immunofluorescent intensity of doublecortin (DCX) was conducted to evaluate the 
      development of neurons in hippocampus. Morris water maze and Y-maze test were 
      used to assess cognitive functions and open-field test and elevated plus maze 
      were used to detect anxiety-like behaviors 4 weeks after seizure onset.Results: 
      mTOR pathway was abnormally activated with two peaks after pilocarpine-induced 
      seizures, and no difference of DCX-positive cells and body weight were noticed 
      between control and pilocarpine-induced seizure rats. Pilocarpine-induced seizure 
      in postnatal 10 days rats did not exert impairment on cognitive functions, but 
      resulted in obvious anxiety-like behaviors. Low dose of rapamycin at 0.3 mg/kg 
      significantly reversed seizure-induced increase of p-S6 levels as well as 
      abnormal anxiety-like behaviors. In addition, rapamycin at the dose of 0.3mg/kg 
      did not affect normal development and cognitive functions.Conclusion: lower doses 
      of rapamycin should be used in infants compared with older children or adults.
FAU - Liu, Furong
AU  - Liu F
AD  - Department of Pharmacy, School of Medicine, Zhejiang University City College, 
      Hangzhou, Zhejiang, China.
AD  - Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, 
      Zhejiang, China.
FAU - Wu, Meiling
AU  - Wu M
AD  - Department of Pharmacy, School of Medicine, Zhejiang University City College, 
      Hangzhou, Zhejiang, China.
AD  - Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, 
      Zhejiang, China.
FAU - Kai, Jiejing
AU  - Kai J
AD  - Department of Pharmacy, School of Medicine, Zhejiang University City College, 
      Hangzhou, Zhejiang, China.
AD  - Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, 
      Zhejiang, China.
FAU - Dong, Jingyin
AU  - Dong J
AD  - Department of Pharmacy, School of Medicine, Zhejiang University City College, 
      Hangzhou, Zhejiang, China.
FAU - Zhang, Binbin
AU  - Zhang B
AD  - Department of Pharmacy, School of Medicine, Zhejiang University City College, 
      Hangzhou, Zhejiang, China.
FAU - Liu, Luna
AU  - Liu L
AD  - Department of Pharmacy, School of Medicine, Zhejiang University City College, 
      Hangzhou, Zhejiang, China.
FAU - Zhu, Feng
AU  - Zhu F
AD  - Department of Pharmacy, School of Medicine, Zhejiang University City College, 
      Hangzhou, Zhejiang, China.
FAU - Zeng, Ling-Hui
AU  - Zeng LH
AD  - Department of Pharmacy, School of Medicine, Zhejiang University City College, 
      Hangzhou, Zhejiang, China.
AD  - Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, 
      Zhejiang, China.
LA  - eng
PT  - Journal Article
DEP - 20191010
PL  - England
TA  - Int J Neurosci
JT  - The International journal of neuroscience
JID - 0270707
RN  - 0 (Dcx protein, rat)
RN  - 0 (Doublecortin Protein)
RN  - 0 (Ribosomal Protein S6)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Cognitive Dysfunction/*prevention & control
MH  - Dose-Response Relationship, Drug
MH  - Doublecortin Protein
MH  - Hippocampus/metabolism
MH  - Male
MH  - Neurogenesis/*drug effects
MH  - Neurons/drug effects
MH  - Pilocarpine
MH  - Rats
MH  - Ribosomal Protein S6/biosynthesis
MH  - Seizures/chemically induced/psychology
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Anxiety-like behaviors
OT  - cognitive function
OT  - immature rats
OT  - rapamycin
OT  - seizure
EDAT- 2018/06/09 06:00
MHDA- 2020/07/15 06:00
CRDT- 2018/06/09 06:00
PHST- 2018/06/09 06:00 [pubmed]
PHST- 2020/07/15 06:00 [medline]
PHST- 2018/06/09 06:00 [entrez]
AID - 10.1080/00207454.2018.1486827 [doi]
PST - ppublish
SO  - Int J Neurosci. 2020 Jan;130(1):9-18. doi: 10.1080/00207454.2018.1486827. Epub 
      2019 Oct 10.