3-mercaptopropionic acid-induced seizures decrease NR2B expression in Purkinje cells: cyclopentyladenosine effect.
Inhibitory mechanism of cerebellum epileptic activity can be involved depending on the intensity and frequency of seizure convulsions. N-methyl-D-aspartate receptors (NMDARs) play key roles in excitatory synaptic transmission and have been implicated in neurological disorders: in cerebellum, they have specific characteristics. NMDARs are heteromeric complexes, and the expression of functional receptors in mammalian cells requires the subunit NR1 (essential) and one NR2 subtype of the four isoforms: NR2A-NR2D. In mature Purkinje cells, the combination of NR1 with NR2B subunits forms functional NMDARs; NR2B subunit may be altered in exocitotoxic events. Cyclopentyladenosine (CPA), an adenosine analogue, administered to rats, for one or more days, increases seizure threshold induced by the convulsant drug 3-mercaptopropionic acid (MP). In this study, we focused on the expression of NR2B in cerebellum after repetitive seizures induced by MP and the effect of adenosine analogue CPA administered alone or previous to MP (CPA + MP). A significant decrease in NR2B in the whole cerebellum was observed after MP and CPA administration with a tendency to recover to normal values in the combined treatment of CPA administered 30 min before MP by Western blot assay. In immunohistochemical studies, NR2B expression was observed and analysed in Purkinje cells. NR2B expression was decreased after MP (55%) and CPA (12%) administration, and CPA injected 30 min before MP led to 28% reduction in Purkinje cells. These results could be related to Purkinje cell damage or alternatively to avoid the excitotoxic effect. Results recorded after CPA + MP treatment seemed involved in decreasing the convulsant MP effect.
Girardi
E
E
Instituto de Biología Celular y Neurociencia, Facultad de Medicina, Universidad de Buenos Aires and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Paraguay 2155, Buenos Aires, Argentina. egirardi@retina.ar
Auzmendi
J
J
Charó
N
N
Gori
M B
MB
Castro
M
M
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology*; D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D003292:Convulsants / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism
D003292:Convulsants; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D015097:3-Mercaptopropionic Acid; D000241:Adenosine