Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy.
OBJECTIVE
The endocannabinoid system is involved in excitatory/inhibitory balance mechanisms within the central nervous system (CNS). Growing evidence shows that its perturbation leads to development of epileptic seizures in experimental models, thus indicating that endocannabinoids play an intrinsic protective role in suppressing pathologic neuronal excitability. Experimental data also demonstrate that the endocannabinoid anandamide (AEA) can antagonize epileptic discharges in hippocampal tissue. The objective of our study was to measure endocannabinoids levels in the cerebrospinal fluid (CSF) of drug-naive patients affected by temporal lobe epilepsy (TLE).


METHODS
We measured the levels of both AEA and the other endocannabinoid, 2-arachidonoylglycerol (2-AG), in the CSF of drug-naive patients with TLE.


RESULTS
A significant reduction of AEA was found in the CSF of patients with compared with healthy controls (epileptic patients = 2.55 +/- 1.78 pmol/ml; healthy controls = 11.65 +/- 7.53 pmol/ml; n = 9 for both groups, p < 0.01). 2-AG levels, however, were not affected (epileptic patients = 209.5 +/- 146.56; healthy controls = 159.6 +/- 110.2) (n = 6 for both groups, p = 0.48).


CONCLUSIONS
Our findings seem to be consistent with experimental evidence demonstrating a significant prevention of epileptic seizures induced by endocannabinoids in models of epilepsy. Furthermore, they support the hypothesis that AEA may be involved in its pathogenesis, suggesting a hypothetical primary impairment of the endocannabinoid system in untreated TLE. The actual role of this in vivo dysregulation still remains unclear.
Romigi
Andrea
A
Dipartimento di Neuroscienze, Università degli Studi di Roma Tor Vergata, Roma, Italy. a_romigi@inwind.it
Bari
Monica
M
Placidi
Fabio
F
Marciani
M Grazia
MG
Malaponti
Marilena
M
Torelli
Federico
F
Izzi
Francesca
F
Prosperetti
Chiara
C
Zannino
Silvana
S
Corte
Francesca
F
Chiaramonte
Carlo
C
Maccarrone
Mauro
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001095:Arachidonic Acids / Q000134:cerebrospinal fluid* / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000032:analysis / Q000134:cerebrospinal fluid* / Q000502:physiology; D004195:Disease Models, Animal; D063388:Endocannabinoids; D004827:Epilepsy / Q000134:cerebrospinal fluid / Q000503:physiopathology / Q000517:prevention & control; D004833:Epilepsy, Temporal Lobe / Q000134:cerebrospinal fluid* / Q000503:physiopathology* / Q000517:prevention & control; D005260:Female; D005989:Glycerides / Q000134:cerebrospinal fluid / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D053284:Polyunsaturated Alkamides / Q000134:cerebrospinal fluid*; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000502:physiology
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C094503:glyceryl 2-arachidonate; C078814:anandamide