PMID- 26113375
OWN - NLM
STAT- MEDLINE
DCOM- 20160607
LR  - 20220317
IS  - 1872-7077 (Electronic)
IS  - 1382-6689 (Linking)
VI  - 40
IP  - 1
DP  - 2015 Jul
TI  - Astrocyte activation and neurotoxicity: A study in different rat brain regions 
      and in rat C6 astroglial cells.
PG  - 122-39
LID - S1382-6689(15)30002-8 [pii]
LID - 10.1016/j.etap.2015.06.001 [doi]
AB  - The present study was conducted to investigate the effect of rotenone on 
      astrocytes activation, their viability and its effect on neuronal death in 
      different brain regions. Rotenone was injected in rat brain by 
      intracerebroventricularly (bilateral) route at dose of 6 mug and 12 mug. In vitro 
      C6 cells were treated with rotenone at concentration of 0.1, 0.25, 0.5, 1 and 2 
      muM. Rotenone administration to rat brain caused significant astrocytes activation 
      in frontal cortex, cerebellum, cerebellar nucleus, substantia nigra, hypothalamus 
      and hippocampus regions of the rat brain. Rotenone administration also led to 
      significant degeneration of cells in all the studied regions along with altered 
      nuclear morphology assessed by hematoxylin-eosin and cresyl violet staining. 
      Histological staining showed the significantly decreased number of cells in all 
      the studied regions except cerebellar nucleus in dose and time dependant manner. 
      Rotenone administration in the rat brain also caused significant decrease in 
      glutathione levels and augmented nitrite levels. In vitro treatment of rotenone 
      to astrocytic C6 cells caused significantly increased expression of glial 
      fibrillar acidic protein (GFAP) and decreased viability in dose and time 
      dependent manner. Rotenone treatment to C6 cells exhibited significant generation 
      of reactive oxygen species, augmented nitrite level, impaired mitochondrial 
      activity, apoptotic chromatin condensation and DNA damage in comparison to 
      control cells. Findings showed that oxidative stress play a considerable role in 
      rotenone induced astrocyte death that was attenuated with co-treatment of 
      antioxidant melatonin. In conclusion, results showed that rotenone caused 
      significant astrocytes activation, altered nuclear morphology, biochemical 
      alteration and apoptotic cell death in different rat brain regions. In vitro 
      observations in C6 cells showed that rotenone treatment exhibited oxidative 
      stress mediated apoptotic cell death, which was attenuated with co treatment of 
      melatonin.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Goswami, Poonam
AU  - Goswami P
AD  - Toxicology Division, CSIR-CDRI, Lucknow 226031, India; Academy of Scientific & 
      Innovative Research (AcSIR), India.
FAU - Gupta, Sonam
AU  - Gupta S
AD  - Toxicology Division, CSIR-CDRI, Lucknow 226031, India; Academy of Scientific & 
      Innovative Research (AcSIR), India.
FAU - Joshi, Neeraj
AU  - Joshi N
AD  - Department of Biochemistry and Biophysics, University of California, San 
      Francisco, CA, USA.
FAU - Sharma, Sharad
AU  - Sharma S
AD  - Toxicology Division, CSIR-CDRI, Lucknow 226031, India.
FAU - Singh, Sarika
AU  - Singh S
AD  - Toxicology Division, CSIR-CDRI, Lucknow 226031, India; Academy of Scientific & 
      Innovative Research (AcSIR), India. Electronic address: sarika_singh@cdri.res.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150604
PL  - Netherlands
TA  - Environ Toxicol Pharmacol
JT  - Environmental toxicology and pharmacology
JID - 9612020
RN  - 0 (Nitrites)
RN  - 03L9OT429T (Rotenone)
RN  - GAN16C9B8O (Glutathione)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
EIN - Environ Toxicol Pharmacol. 2022 Jan;89:103758. PMID: 34776397
MH  - Animals
MH  - Astrocytes/cytology/*drug effects
MH  - Brain/cytology/*drug effects/metabolism
MH  - Cells, Cultured
MH  - Glutathione/metabolism
MH  - Melatonin/pharmacology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mice
MH  - Nitrites/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rotenone/pharmacology
OTO - NOTNLM
OT  - Astrocyte activation
OT  - DNA damage
OT  - Melatonin
OT  - Nitrite level
OT  - Reactive oxygen species
OT  - Rotenone
EDAT- 2015/06/27 06:00
MHDA- 2016/06/09 06:00
CRDT- 2015/06/27 06:00
PHST- 2015/01/05 00:00 [received]
PHST- 2015/05/29 00:00 [revised]
PHST- 2015/06/01 00:00 [accepted]
PHST- 2015/06/27 06:00 [entrez]
PHST- 2015/06/27 06:00 [pubmed]
PHST- 2016/06/09 06:00 [medline]
AID - S1382-6689(15)30002-8 [pii]
AID - 10.1016/j.etap.2015.06.001 [doi]
PST - ppublish
SO  - Environ Toxicol Pharmacol. 2015 Jul;40(1):122-39. doi: 
      10.1016/j.etap.2015.06.001. Epub 2015 Jun 4.