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Intrinsic up-regulation of 2-AG favors an area specific neuronal survival in different in vitro models of neuronal damage

Kallendrusch, Sonja ; Hobusch, Constance ; Ehrlich, Angela ; Nowicki, Marcin ; Ziebell, Simone ; Bechmann, Ingo ; Geisslinger, Gerd ; Koch, Marco ; Dehghani, Faramarz Rameshwar, Pranela

PloS one, 2012-12, Vol.7 (12), p.e51208 [Peer Reviewed Journal]

United States: Public Library of Science

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Title:
Intrinsic up-regulation of 2-AG favors an area specific neuronal survival in different in vitro models of neuronal damage
Author: Kallendrusch, Sonja ; Hobusch, Constance ; Ehrlich, Angela ; Nowicki, Marcin ; Ziebell, Simone ; Bechmann, Ingo ; Geisslinger, Gerd ; Koch, Marco ; Dehghani, Faramarz
Rameshwar, Pranela
Subjects: Alzheimer's disease ; Animals ; Arachidonic Acids - metabolism ; Astrocytes ; Astrocytes - cytology ; Astrocytes - drug effects ; Astrocytes - metabolism ; Benzodioxoles - pharmacology ; Biology ; Brain ; Brain slice preparation ; Cannabinoids ; Cell culture ; Cell cycle ; Cell survival ; Cell Survival - drug effects ; Cortex (temporal) ; Dentate gyrus ; Diglycerides ; Endocannabinoids - metabolism ; Enzymes ; Ethics ; Excitotoxicity ; Female ; Gene expression ; Gene Knockdown Techniques ; Glycerides - metabolism ; Glycerin ; Glycerol ; Hippocampus ; Hippocampus - cytology ; Ischemia ; Lesions ; Lipase ; Lipoprotein lipase ; Lipoprotein Lipase - metabolism ; Medicine ; Metabolism ; Microglia ; Microglia - cytology ; Microglia - drug effects ; Microglia - metabolism ; Monoacylglycerol Lipases - deficiency ; Monoacylglycerol Lipases - genetics ; Monoacylglycerol Lipases - metabolism ; N-Methylaspartate - toxicity ; Neurodegeneration ; Neurons ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; Neuroprotection ; Penicillin ; Perforant Pathway - cytology ; Perforant Pathway - drug effects ; Perforant Pathway - metabolism ; Physiological aspects ; Physiological effects ; Piperidines - pharmacology ; Protein Transport - drug effects ; Rats, Wistar ; RNA ; Rodents ; Signaling ; Transcription, Genetic - drug effects ; Traumatic brain injury ; Up-regulation ; Up-Regulation - drug effects
Is Part Of: PloS one, 2012-12, Vol.7 (12), p.e51208
Notes: Conceived and designed the experiments: SK GG MK FD. Performed the experiments: SK AE CH. Analyzed the data: SK MK FD. Contributed reagents/materials/analysis tools: GG MN IB SZ. Wrote the paper: SK MK FD.
Competing Interests: The authors have declared that no competing interests exist.
Description: The endocannabinoid 2-arachidonoyl glycerol (2-AG) acts as a retrograde messenger and modulates synaptic signaling e. g. in the hippocampus. 2-AG also exerts neuroprotective effects under pathological situations. To better understand the mechanism beyond physiological signaling we used Organotypic Entorhino-Hippocampal Slice Cultures (OHSC) and investigated the temporal regulation of 2-AG in different cell subsets during excitotoxic lesion and dendritic lesion of long range projections in the enthorhinal cortex (EC), dentate gyrus (DG) and the cornu ammonis region 1 (CA1). 2-AG levels were elevated 24 h after excitotoxic lesion in CA1 and DG (but not EC) and 24 h after perforant pathway transection (PPT) in the DG only. After PPT diacylglycerol lipase alpha (DAGL) protein, the synthesizing enzyme of 2-AG was decreased when Dagl mRNA expression and 2-AG levels were enhanced. In contrast to DAGL, the 2-AG hydrolyzing enzyme monoacylglycerol lipase (MAGL) showed no alterations in total protein and mRNA expression after PPT in OHSC. MAGL immunoreaction underwent a redistribution after PPT and excitotoxic lesion since MAGL IR disappeared in astrocytes of lesioned OHSC. DAGL and MAGL immunoreactions were not detectable in microglia at all investigated time points. Thus, induction of the neuroprotective endocannabinoid 2-AG might be generally accomplished by down-regulation of MAGL in astrocytes after neuronal lesions. Increase in 2-AG levels during secondary neuronal damage reflects a general neuroprotective mechanism since it occurred independently in both different lesion models. This intrinsic up-regulation of 2-AG is synergistically controlled by DAGL and MAGL in neurons and astrocytes and thus represents a protective system for neurons that is involved in dendritic reorganisation.
Publisher: United States: Public Library of Science
Language: English

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Intrinsic up-regulation of 2-AG favors an area specific neuronal survival in different in vitro models of neuronal damage

Kallendrusch, Sonja ; Hobusch, Constance ; Ehrlich, Angela ; Nowicki, Marcin ; Ziebell, Simone ; Bechmann, Ingo ; Geisslinger, Gerd ; Koch, Marco ; Dehghani, Faramarz Rameshwar, Pranela

United States: Public Library of Science

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