11Beta-hydroxysteroid dehydrogenase type 1 activity in medial vestibular nucleus and cerebellum after unilateral vestibular deafferentation in the rat.
In the early stages of vestibular compensation (VC) (the behavioural recovery that follows unilateral vestibular deafferentation), neurons in the medial vestibular nucleus (MVN) on the lesioned side develop a sustained up-regulation of their intrinsic excitability. This plasticity is dependent on the activation of glucocorticoid receptors, which presumably occurs during the acute stress response that accompanies the vestibular deafferentation symptoms. Recent studies have established that the access of glucocorticoids to their intracellular receptors in brain is potently modulated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which catalyses the generation of active glucocorticoids from their inert 11-keto forms. In this study, we investigated the presence of 11beta-HSD1 bioactivity, and possible changes in activity in the early stage after vestibular deafferentation, in the cerebellar nodulus and uvula, the flocculus/paraflocculus (F/PF) complex and the MVN of the rat. 11beta-HSD1 activity was found in each of these brain areas, with especially high levels of activity in the F/PF complex. No differences were found in the level of 11beta-HSD1 activity in these brain areas between control rats, sham-operated rats and rats that underwent VC for 4 h after unilateral vestibular deafferentation. These findings demonstrate 11beta-HSD1 bioactivity in the MVN and vestibulocerebellum, but exclude the possibility that changes in 11beta-HSD1 activity occur in the early period after deafferentation, over the time when changes in MVN neuronal properties take place.
Guilding
Clare
C
Biomedical Sciences, Hugh Robson Building, George Square, Edinburgh, EH8 9XD UK.
Seckl
Jonathan R
JR
Dutia
Mayank B
MB
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000344:Afferent Pathways; D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D003714:Denervation; D008297:Male; D009473:Neuronal Plasticity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014726:Vestibular Nuclei / Q000378:metabolism*
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1