PMID- 19818836
OWN - NLM
STAT- MEDLINE
DCOM- 20100201
LR  - 20220408
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 467
IP  - 2
DP  - 2009 Dec 25
TI  - BDNF regulates neuronal sensitivity to endocannabinoids.
PG  - 90-4
LID - 10.1016/j.neulet.2009.10.011 [doi]
AB  - The diacylglycerol lipases (DAGLalpha/beta) synthesize 2-arachidonylglycerol 
      (2-AG), the major endocannabinoid in the developing and adult brain (eCB). This 
      lipid acts on cannabinoid receptors to regulate axonal growth and guidance, 
      activity-dependent synaptic plasticity and adult neurogenesis, and can also 
      protect neurons from excitotoxicity. 2-AG action is generally terminated by 
      monoacylglycerol lipase (MAGL), however we know very little about the mechanisms 
      that regulate neuronal sensitivity to eCBs. In the present study we show that the 
      brain-derived neurotrophic factor (BDNF) can determine neuronal sensitivity to 
      eCBs. In this context, in cultured cerebellar granule neurons (CGNs) BDNF 
      increases the expression of CB1 receptor transcripts and decreases expression of 
      MAGL transcripts. Using phosphorylation of Akt as the readout, we show that BDNF 
      can promote a stable increase in neuronal sensitivity to eCBs. For example, 
      concentrations of 2-AG and noladin either (NE) that normally do not lead to Akt 
      phosphorylation in control neurons do so in neurons pre-treated with BDNF. In 
      addition, Akt phosphorylation in response to a wide range of concentrations of NE 
      was always greater in neurons pre-treated with BDNF. Our data suggests the 
      existence of a positive feedback loop that might sustain neuronal survival in the 
      normal brain.
FAU - Maison, Patrick
AU  - Maison P
AD  - Wolfson Centre for Age-Related Diseases, King' College London, London Bridge, 
      London SE1 1UL, United Kingdom.
FAU - Walker, Deborah J
AU  - Walker DJ
FAU - Walsh, Frank S
AU  - Walsh FS
FAU - Williams, Gareth
AU  - Williams G
FAU - Doherty, Patrick
AU  - Doherty P
LA  - eng
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091008
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Arachidonic Acids)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cannabinoid Receptor Modulators)
RN  - 0 (Endocannabinoids)
RN  - 0 (Glycerides)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0D295FLV8W (noladin ether)
RN  - 8D239QDW64 (glyceryl 2-arachidonate)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.1.23 (Monoacylglycerol Lipases)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Arachidonic Acids/pharmacology/physiology
MH  - Brain-Derived Neurotrophic Factor/pharmacology/*physiology
MH  - Cannabinoid Receptor Modulators/*biosynthesis/genetics
MH  - Cells, Cultured
MH  - Cerebellum/cytology
MH  - Down-Regulation
MH  - *Endocannabinoids
MH  - Glycerides/pharmacology/physiology
MH  - Monoacylglycerol Lipases/biosynthesis/genetics
MH  - Neurons/drug effects/*metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Receptor, Cannabinoid, CB1/biosynthesis/genetics
MH  - Up-Regulation
EDAT- 2009/10/13 06:00
MHDA- 2010/02/02 06:00
CRDT- 2009/10/13 06:00
PHST- 2009/08/04 00:00 [received]
PHST- 2009/09/02 00:00 [revised]
PHST- 2009/10/04 00:00 [accepted]
PHST- 2009/10/13 06:00 [entrez]
PHST- 2009/10/13 06:00 [pubmed]
PHST- 2010/02/02 06:00 [medline]
AID - S0304-3940(09)01311-1 [pii]
AID - 10.1016/j.neulet.2009.10.011 [doi]
PST - ppublish
SO  - Neurosci Lett. 2009 Dec 25;467(2):90-4. doi: 10.1016/j.neulet.2009.10.011. Epub 
      2009 Oct 8.