Plasticity of GABA(a) system during ageing: focus on vestibular compensation and possible pharmacological intervention.
The lesion of the vestibular end organ evokes static and dynamic symptoms, which spontaneously regress during a complex process known as 'vestibular compensation'. Vestibular compensation is age-dependent and involves several transmitter-identified pathways in the central nervous system. In this paper we studied the time course of vestibular compensation in adult (3 months) and old (24 months) rats and correlated behavioral recovery with modifications of glutamic acid decarboxylase (GAD) mRNA expression and benzodiazepine receptor density in different brain areas. Compensation in adult rats was complete 28 days after hemilabyrinthectomy, whereas old rats still showed significant behavioral impairment. A higher GABAergic tone was found in old rats, as indicated by higher benzodiazepine receptor density in lateral vestibular nucleus and higher mRNA level for glutamic acid decarboxylase in cerebral cortex and medial vestibular nucleus. In adult, compensated rats, benzodiazepine receptor density in the vestibular nuclei was normal 28 days after lesion, whereas GAD mRNA level was higher in anterior cingulate cortex, only. On the contrary, these parameters were still altered in anterior cingulate and somatosensory cortex, basal ganglia, vestibular nuclei and cerebellum in old rats 28 days after vestibular lesion. We also evaluated the effect of the ergoline derivative nicergoline on behavioral and neurochemical correlates of vestibular compensation in old rats. Nicergoline treatment attenuated the severity of oculomotor and postural symptoms after vestibular lesion and reversed most of these age- and lesion-induced alterations in GAD mRNA expression. Thus, lesion-related alterations of the GABAergic transmission and behavioral profile after vestibular lesion are age-dependent.
Giardino
Luciana
L
Department of Veterinary Morphophysiology and Animal Production (DIMORFIPA), Università di Bologna, Via Tolara di Sopra 50, 40064 Ozzano dell'Emilia, Bologna, Italy. lgiardino@vet.unibo.it
Zanni
Massimo
M
Fernandez
Mercedes
M
Battaglia
Angelo
A
Pignataro
Oreste
O
Calzà
Laura
L
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005445:Flunitrazepam; D018757:GABA Modulators; D005968:Glutamate Decarboxylase / Q000235:genetics; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009530:Nicergoline / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015837:Vestibular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D014722:Vestibule, Labyrinth / Q000293:injuries / Q000503:physiopathology* / Q000601:surgery; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018757:GABA Modulators; D018697:Nootropic Agents; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D005968:Glutamate Decarboxylase; D009530:Nicergoline