title: Endocannabinoid-hydrolysing enzymes in the post-mortem cerebellum of humans affected by hereditary autosomal dominant ataxias.
abstract: OBJECTIVE
  Spinocerebellar ataxias (SCAs) are characterized by a loss of balance and motor coordination due to degeneration of the cerebellum and its afferent and efferent connections. We recently found important changes in cannabinoid CB1 and CB2 receptors in the post-mortem cerebellum of patients affected by different SCAs.
  
  
  METHODS
  We wanted to further explore this issue by analysing the two major endocannabinoid-hydrolysing enzymes, fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL), in the post-mortem cerebellum of SCA patients and control subjects.
  
  
  RESULTS
  Immunoreactivity for the FAAH and MAGL enzymes was found in the granular layer, in Purkinje cells, in neurons of the dentate nucleus and in areas of white matter in the cerebellum of patients at levels frequently notably higher than those in control subjects. Using double-labelling procedures, we found co-localization of FAAH and MAGL with calbindin, supporting the presence of these enzymes in Purkinje neurons.
  
  
  CONCLUSIONS
  Degradative endocannabinoid enzymes are significantly increased in the cerebellum of SCA patients, which would presumably lead to reduced endocannabinoid levels. The identification of these enzymes in Purkinje neurons suggests a relationship with the pathogenesis of SCAs and suggests that the endocannabinoid system could provide potential therapeutic targets for the treatment of disease progression in SCAs.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodríguez-Cueto
authors.forename: Cristina
authors.initials: C
authors.lastname: Benito
authors.forename: Julián
authors.initials: J
authors.lastname: Romero
authors.forename: Mariluz
authors.initials: M
authors.lastname: Hernández-Gálvez
authors.forename: María
authors.initials: M
authors.lastname: Gómez-Ruiz
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández-Ruiz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000581:Amidohydrolases / Q000378:metabolism*; D001344:Autopsy; D016022:Case-Control Studies; D002529:Cerebellar Nuclei / Q000378:metabolism / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged; D008994:Monoacylglycerol Lipases / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000378:metabolism* / Q000473:pathology; D066127:White Matter / Q000378:metabolism / Q000473:pathology; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D063388:Endocannabinoids; D008994:Monoacylglycerol Lipases; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases