Abstract:
:To date, the neurochemical basis underlying the motor and cognitive deficits described in patients with multiple sclerosis (MS) is unclear. Since the neuropeptide somatostatin (SRIF) and the striatum have been implicated in movement control and implicit memory, the aim of this study was to analyze the striatal somatostatinergic system in an animal model of MS, experimental autoimmune encephalomyelitis (EAE). Female Lewis rats were immunized with an emulsion containing myelin basic protein (MBP) in complete Freund's adjuvant to induce the disease. The animals were decapitated when limp tail (grade 1) or severe hind limb paralysis (grade 3) was observed. Acute EAE in grade 3 did not modify striatal somatostatin-like immunoreactivity (SRIF-LI) content but decreased the overall SRIF receptor density, without affecting the apparent affinity, in the rat striatal membranes. A selective reduction in the protein levels of the SRIF receptor subtype sst2, analyzed by Western blotting, was detected in the EAE rats, which correlated with decreased sst2 mRNA levels. The expression of the receptor subtypes sst1, sst3 or sst4 was unaltered by the disease. The decrease in the SRIF receptor density was accompanied by an attenuated capacity of SRIF to inhibit both basal and forskolin-stimulated adenylyl cyclase activity. No significant changes, however, were found in the protein levels of Gi proteins (G(ialpha1), G(ialpha2) or G(ialpha3)) nor in those of the G-protein-coupled receptor kinase subtypes GRK2, GRK5 or GRK6. Acute EAE in grade 1 did not modify any of the parameters studied. In conclusion, these data demonstrate that acute EAE, in grade 3, disrupts the rat striatal SRIF receptor-effector system. These findings provide new insight into the molecular basis of EAE which might contribute to a better understanding of multiple sclerosis in humans.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Aguado-Llera D,Puebla-Jiménez L,Yébenes-Gregorio L,Arilla-Ferreiro Edoi
10.1016/j.neuroscience.2007.04.065subject
Has Abstractpub_date
2007-08-10 00:00:00pages
238-49issue
1eissn
0306-4522issn
1873-7544pii
S0306-4522(07)00519-2journal_volume
148pub_type
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