PMID- 23550806
OWN - NLM
STAT- MEDLINE
DCOM- 20140121
LR  - 20220321
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 37
IP  - 8
DP  - 2013 Aug
TI  - Cyclic adenosine monophosphate and brain-derived neurotrophic factor decreased 
      oxidative stress and apoptosis in developing hypothalamic neuronal cells: role of 
      microglia.
PG  - 1370-9
LID - 10.1111/acer.12104 [doi]
AB  - BACKGROUND: We have previously shown that ethanol (EtOH) increases cellular 
      apoptosis to developing neurons via the effects on oxidative stress of neurons 
      directly and via increasing production of microglia-derived factors. To study 
      further the mechanism of EtOH action on neuronal apoptosis, we determined the 
      effects of 2 well-known PKA activators, dibutyryl cAMP (dbcAMP) and brain-derived 
      neurotrophic factor (BDNF), on EtOH-activated oxidative stress and apoptotic 
      processes in the hypothalamic neurons in the presence and absence of microglial 
      cells' influence. METHODS: In enriched neuronal cells from fetal rat hypothalami 
      treated with EtOH or with conditioned medium from EtOH-treated microglia, we 
      measured cellular apoptosis by the free nucleosome assay and the levels of cAMP, 
      BDNF, O(2)(-), reactive oxygen species (ROS), nitrite, glutathione (GSH), and 
      catalase following treatment with EtOH or EtOH-treated microglial culture 
      conditioned medium. Additionally, we tested the effectiveness of dbcAMP and BDNF 
      in preventing EtOH or EtOH-treated microglial conditioned medium on cellular 
      apoptosis and oxidative stress in enriched hypothalamic neuronal cell in primary 
      cultures. RESULTS: Neuronal cell cultures following treatment with EtOH or 
      EtOH-activated microglial conditioned medium showed decreased production levels 
      of cAMP and BDNF. EtOH also increased apoptotic death as well as oxidative 
      status, as demonstrated by higher cellular levels of oxidants but lower levels of 
      antioxidants, in neuronal cells. These effects of EtOH on oxidative stress and 
      cell death were enhanced by the presence of microglia. Treatment with BDNF or 
      dbcAMP decreased EtOH or EtOH-activated microglial conditioned medium-induced 
      changes in the levels of intracellular free radicals, ROS and O(2)(-), nitrite, GSH, 
      and catalase. CONCLUSIONS: These data support the possibility that EtOH by acting 
      directly and via increasing the production of microglial-derived factors reduces 
      cellular levels of cAMP and BDNF to increase cellular oxidative status and 
      apoptosis in hypothalamic neuronal cells in primary cultures.
CI  - Copyright (c) 2013 by the Research Society on Alcoholism.
FAU - Boyadjieva, Nadka I
AU  - Boyadjieva NI
AD  - Endocrine Program, Department of Animal Sciences, Graduate Program of 
      Neuroscience, Rutgers, The State University of New Jersey, New Brunswick, NJ, 
      USA.
FAU - Sarkar, Dipak K
AU  - Sarkar DK
LA  - eng
GR  - R37 AA008757/AA/NIAAA NIH HHS/United States
GR  - R37 AA08757/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130329
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Antioxidants)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Central Nervous System Depressants)
RN  - 3K9958V90M (Ethanol)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Apoptosis/immunology
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Cells, Cultured
MH  - Central Nervous System Depressants/adverse effects
MH  - Cyclic AMP/*physiology
MH  - Ethanol/adverse effects/*metabolism
MH  - Female
MH  - Fetal Alcohol Spectrum Disorders/etiology
MH  - Hypothalamus/drug effects/*metabolism
MH  - Microglia/drug effects/*physiology
MH  - Oxidative Stress/immunology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Up-Regulation/physiology
PMC - PMC3706564
MID - NIHMS439136
OTO - NOTNLM
OT  - Apoptosis
OT  - BDNF
OT  - Microglia
OT  - Neurons
OT  - Oxidative Stress
OT  - cAMP
EDAT- 2013/04/05 06:00
MHDA- 2014/01/22 06:00
PMCR- 2014/08/01
CRDT- 2013/04/05 06:00
PHST- 2012/08/26 00:00 [received]
PHST- 2013/01/12 00:00 [accepted]
PHST- 2013/04/05 06:00 [entrez]
PHST- 2013/04/05 06:00 [pubmed]
PHST- 2014/01/22 06:00 [medline]
PHST- 2014/08/01 00:00 [pmc-release]
AID - 10.1111/acer.12104 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2013 Aug;37(8):1370-9. doi: 10.1111/acer.12104. Epub 2013 
      Mar 29.