title: Effect of inhibition of fatty acid amide hydrolase on MPTP-induced dopaminergic neuronal damage.
abstract: BACKGROUND
  Parkinson's disease (PD) is a neurodegenerative disorder characterised by balance problems, muscle rigidity, and slow movement due to low dopamine levels and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The endocannabinoid system is known to modulate the nigrostriatal pathway through endogenous ligands such as anandamide (AEA), which is hydrolysed by fatty acid amide hydrolase (FAAH). The purpose of this study was to increase AEA levels using FAAH inhibitor URB597 to evaluate the modulatory effect of AEA on dopaminergic neuronal death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
  
  
  METHODS
  Our study included 4 experimental groups (n = 6 mice per group): a control group receiving no treatment, a group receiving URB597 (0.2mg/kg) every 3 days for 30 days, a group treated with MPTP (30mg/kg) for 5 days, and a group receiving URB597 and subsequently MPTP injections. Three days after the last dose, we conducted a series of behavioural tests (beam test, pole test, and stride length test) to compare motor coordination between groups. We subsequently analysed immunoreactivity of dopaminergic cells and microglia in the SNpc and striatum.
  
  
  RESULTS
  Mice treated with URB597 plus MPTP were found to perform better on behavioural tests than mice receiving MPTP only. According to the immunohistochemistry study, mice receiving MPTP showed fewer dopaminergic cells and fibres in the SNpc and striatum. Animals treated with URB597 plus MPTP displayed increased tyrosine hydroxylase immunoreactivity compared to those treated with MPTP only. Regarding microglial immunoreactivity, the group receiving MPTP showed higher Iba1 immunoreactivity in the striatum and SNpc than did the group treated with URB597 plus MPTP.
  
  
  CONCLUSIONS
  Our results show that URB597 exerts a protective effect since it inhibits dopaminergic neuronal death, decreases microglial immunoreactivity, and improves MPTP-induced motor alterations.
authors.affiliation: Departamento de Farmacobiología CUCEI, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: J M
authors.initials: JM
authors.lastname: Viveros-Paredes
authors.affiliation: Laboratorio de Microscopía de Alta Resolución, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: R E
authors.initials: RE
authors.lastname: Gonzalez-Castañeda
authors.affiliation: Departamento de Farmacobiología CUCEI, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: A
authors.initials: A
authors.lastname: Escalante-Castañeda
authors.affiliation: Departamento de Farmacobiología CUCEI, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: A R
authors.initials: AR
authors.lastname: Tejeda-Martínez
authors.affiliation: Departamento de Farmacobiología CUCEI, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: F
authors.initials: F
authors.lastname: Castañeda-Achutiguí
authors.affiliation: Departamento de Farmacobiología CUCEI, Universidad de Guadalajara, Guadalajara, Jalisco, México; Laboratorio de Inmunodeficiencias y Retrovirus Humanos, Centro de Investigación Biomédica de Occidente, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México. Electronic address: mario.flores@hotmail.es.
authors.forename: M E
authors.initials: ME
authors.lastname: Flores-Soto
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001549:Benzamides; D002219:Carbamates; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009048:Motor Skills / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010300:Parkinson Disease; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000581:Amidohydrolases; D001549:Benzamides; D002219:Carbamates; D018696:Neuroprotective Agents; D014446:Tyrosine 3-Monooxygenase; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
keywords: Cannabinoides; Cannabinoids; Cuerpo estriado, Enfermedad de Parkinson; Neuroprotective; Neuroprotector; Parkinson's disease; Striatum; Substantia nigra; Sustancia nigra