The role of neuroactive steroids and GABA(A) receptors in the generation of spontaneous spike-and-wave discharges (SWDs) was investigated in the WAG/Rij rat model of absence epilepsy. The plasma, cerebrocortical, and thalamic concentrations of the progesterone metabolite 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-TH PROG) were increased in the WAG/Rij rat at 2 months of age compared with those in control (Wistar) rats. In contrast, the brain and peripheral levels of 3 alpha,5 alpha.-tetrahydrodeoxycorticosterone (3 alpha,5 alpha-TH DOC) did not differ between the two rat strains at this age. At 6 months of age, when absence epilepsy worsens in WAG/Rij rats, the plasma concentration of 3 alpha,5 alpha-TH PROG remained high whereas that of 3a,5a-TH DOC had increased, the cerebrocortical levels of both 3 alpha,5 alpha-TH PROG and 3 alpha,5 alpha-TH DOC had increased, and the thalamic concentrations of these metabolites had decreased. At 6 months of age the expression of the 04 and 6 subunits of the GABA(A) receptor in relay nuclei was increased. Finally, chronic stress induced by social isolation elicited a reduction in the amount of 3 alpha,5 alpha-TH PROG in the thalamus of 2-month-old WAG/Rij rats that was associated with a reduction in the number and overall duration of SWDs at 6 months of age. Absence epilepsy in the WAG/Rij rat is thus associated with changes in the abundance of neuroactive steroids and in the expression of specific GABAA receptor subunits in the thalamus, a brain area key to the pathophysiology of this condition.
The role of neuroactive steroids and GABA(A) receptors in the generation of spontaneous spike-and-wave discharges (SWDs) was investigated in the WAG/Rij rat model of absence epilepsy. The plasma, cerebrocortical, and thalamic concentrations of the progesterone metabolite 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-TH PROG) were increased in the WAG/Rij rat at 2 months of age compared with those in control (Wistar) rats. In contrast, the brain and peripheral levels of 3 alpha,5 alpha.-tetrahydrodeoxycorticosterone (3 alpha,5 alpha-TH DOC) did not differ between the two rat strains at this age. At 6 months of age, when absence epilepsy worsens in WAG/Rij rats, the plasma concentration of 3 alpha,5 alpha-TH PROG remained high whereas that of 3a,5a-TH DOC had increased, the cerebrocortical levels of both 3 alpha,5 alpha-TH PROG and 3 alpha,5 alpha-TH DOC had increased, and the thalamic concentrations of these metabolites had decreased. At 6 months of age the expression of the 04 and 6 subunits of the GABA(A) receptor in relay nuclei was increased. Finally, chronic stress induced by social isolation elicited a reduction in the amount of 3 alpha,5 alpha-TH PROG in the thalamus of 2-month-old WAG/Rij rats that was associated with a reduction in the number and overall duration of SWDs at 6 months of age. Absence epilepsy in the WAG/Rij rat is thus associated with changes in the abundance of neuroactive steroids and in the expression of specific GABAA receptor subunits in the thalamus, a brain area key to the pathophysiology of this condition.
Neuroactive steroids and GABA(A) receptor plasticity in the brain of the WAG/Rij rat, a model of absence epilepsy
Russo E;De Sarro G;
2008-01-01
Abstract
The role of neuroactive steroids and GABA(A) receptors in the generation of spontaneous spike-and-wave discharges (SWDs) was investigated in the WAG/Rij rat model of absence epilepsy. The plasma, cerebrocortical, and thalamic concentrations of the progesterone metabolite 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-TH PROG) were increased in the WAG/Rij rat at 2 months of age compared with those in control (Wistar) rats. In contrast, the brain and peripheral levels of 3 alpha,5 alpha.-tetrahydrodeoxycorticosterone (3 alpha,5 alpha-TH DOC) did not differ between the two rat strains at this age. At 6 months of age, when absence epilepsy worsens in WAG/Rij rats, the plasma concentration of 3 alpha,5 alpha-TH PROG remained high whereas that of 3a,5a-TH DOC had increased, the cerebrocortical levels of both 3 alpha,5 alpha-TH PROG and 3 alpha,5 alpha-TH DOC had increased, and the thalamic concentrations of these metabolites had decreased. At 6 months of age the expression of the 04 and 6 subunits of the GABA(A) receptor in relay nuclei was increased. Finally, chronic stress induced by social isolation elicited a reduction in the amount of 3 alpha,5 alpha-TH PROG in the thalamus of 2-month-old WAG/Rij rats that was associated with a reduction in the number and overall duration of SWDs at 6 months of age. Absence epilepsy in the WAG/Rij rat is thus associated with changes in the abundance of neuroactive steroids and in the expression of specific GABAA receptor subunits in the thalamus, a brain area key to the pathophysiology of this condition.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.