PMID- 28983622
OWN - NLM
STAT- MEDLINE
DCOM- 20180626
LR  - 20180626
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 16
IP  - 6
DP  - 2017 Dec
TI  - Novel insights into the effect of paroxetine administration in 
      pilocarpine‑induced chronic epileptic rats.
PG  - 8245-8252
LID - 10.3892/mmr.2017.7659 [doi]
AB  - The aim of the present study was to investigate the role of paroxetine 
      intervention in epilepsy, and its association with the expression of serotonin 
      transporter (SERT) and hippocampal apoptosis. Thirty adult male Sprague Dawley 
      rats were divided into control vehicle (n=6) and epileptic (n=24) groups. Status 
      epilepticus (SE) was induced via systemic injection of pilocarpine, and seizure 
      activity was monitored via video electroencephalogram. The epileptic group was 
      then randomly divided into two groups; Four weeks following SE induction, 
      paroxetine (5 mg/kg/day; SE + paroxetine group) or normal saline (SE group) was 
      intraperitoneally injected for 4 weeks. Brain tissue was collected to evaluate 
      apoptosis via terminal deoxynucleotidyl transferase dUTP nick‑end labeling. SERT, 
      B‑cell lymphoma‑2 (Bcl‑2) and brain derived neurotropic factor (BDNF) expression 
      levels were evaluated by western blotting, and miR‑16 expression was evaluated by 
      reverse transcription‑quantitative polymerase chain reaction. Paroxetine did not 
      affect the mortality of the pilocarpine‑induced chronic epileptic rats. 
      Spontaneous recurrent seizures (SSRs) were observed 7‑28 days following SE 
      induction. The frequency and stage of the SSRs were reduced by paroxetine 
      administration. Apoptotic cells were observed in the epileptic hippocampus. 
      Following paroxetine intervention, the staining intensity and number of apoptotic 
      cells were significantly decreased. Expression levels of BDNF and Bcl‑2 were 
      lower in the SE group compared with the vehicle group. The former was not altered 
      by paroxetine injection; however, the latter was increased. In the SE group, SERT 
      expression was not altered in the raphe nucleus but was decreased in the 
      hippocampus. Following paroxetine administration, SERT expression was decreased 
      in the raphe nucleus and increased in the hippocampus. In the SE group, miR‑16 
      expression was decreased in the raphe nucleus and increased in the hippocampus. 
      Following paroxetine administration, miR‑16 expression was not altered in the 
      raphe nucleus but was reduced in the hippocampus. In conclusion, the seizures and 
      hippocampal apoptosis observed in chronic epileptic rats were alleviated by 
      paroxetine treatment. This effect may be associated with the reduced Bcl‑2 and 
      BDNF expression and the modulation of SERT expression. The alterations in miR‑16 
      expression may provide a potential explanation for the modulation of apoptosis; 
      however, further research is required to determine the complete underlying 
      molecular mechanism.
FAU - Lin, Wan-Hui
AU  - Lin WH
AD  - Department of Neurology and Geriatrics, Union Hospital of Fujian Medical 
      University, Fuzhou, Fujian 350001, P.R. China.
FAU - Li, Xiao-Feng
AU  - Li XF
AD  - Department of Neurology, Union Hospital of Fujian Medical University, Fuzhou, 
      Fujian 350001, P.R. China.
FAU - Lin, Ming-Xing
AU  - Lin MX
AD  - Department of Pediatrics, Union Hospital of Fujian Medical University, Fuzhou, 
      Fujian 350001, P.R. China.
FAU - Zhou, Ying
AU  - Zhou Y
AD  - Neuroscience Research Center of Fujian Medical University, Fuzhou, Fujian 350001, 
      P.R. China.
FAU - Huang, Hua-Pin
AU  - Huang HP
AD  - Department of Neurology and Geriatrics, Union Hospital of Fujian Medical 
      University, Fuzhou, Fujian 350001, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170928
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - 41VRH5220H (Paroxetine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Brain/metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Disease Models, Animal
MH  - Epilepsy/*chemically induced/drug therapy/*physiopathology
MH  - Hippocampus/metabolism/pathology
MH  - Immunohistochemistry
MH  - Male
MH  - Paroxetine/*administration & dosage
MH  - Pilocarpine/*adverse effects
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - Rats
MH  - Serotonin Plasma Membrane Transport Proteins/genetics/metabolism
EDAT- 2017/10/07 06:00
MHDA- 2018/06/27 06:00
CRDT- 2017/10/07 06:00
PHST- 2016/07/12 00:00 [received]
PHST- 2017/05/09 00:00 [accepted]
PHST- 2017/10/07 06:00 [pubmed]
PHST- 2018/06/27 06:00 [medline]
PHST- 2017/10/07 06:00 [entrez]
AID - 10.3892/mmr.2017.7659 [doi]
PST - ppublish
SO  - Mol Med Rep. 2017 Dec;16(6):8245-8252. doi: 10.3892/mmr.2017.7659. Epub 2017 Sep 
      28.