TY - JOUR
T1 - BDNF regulates neuronal sensitivity to endocannabinoids
AU - Maison, Patrick
AU - Walker, Deborah J.
AU - Walsh, Frank S.
AU - Williams, Gareth
AU - Doherty, Patrick
PY - 2009/12/25
Y1 - 2009/12/25
N2 - The diacylglycerol lipases (DAG alpha/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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
AB - The diacylglycerol lipases (DAG alpha/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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
U2 - 10.1016/j.neulet.2009.10.011
DO - 10.1016/j.neulet.2009.10.011
M3 - Article
VL - 467
SP - 90
EP - 94
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -