ABSTRACT
Objective To determine whether the integration of immature neurons born before status epilepticus (SE)can be disrupted by an epileptogenic insult.Methods Pilocarpine was used to induce SE in mice. At week 1 before induction,BrdU or retroviral vector expressing green fluorescent protein (RV-GFP)was used to label the newly born cells in the dentate gyrus (DG).At week 8 after SE,BrdU+Map2 or BrdU+NeuN double-labeling staining was carried out to visualize hilar basal dendrite or hilar ectopic migration.Virus-transduced GFP signals were used to identify the mossy fiber sprouting from the newly generated neurons.The number of cells with aberrant integrations was compared using unpaired Student's t-test.Results The percentage of newborn neurons with aberrant dendritic morphology was (20.8±8.4)% at week 8 after SE.The percentage of BrdU+NeuN double labeled cells ectopically migrated into the hilus was (15.9 ± 7.4)%.At week 8 after SE,the chronically epileptic mice showed many GFP+ processes in the IML with the same axonal appearance and small mossy fiber bouton-like structures as those seen in the hilus.The number of newborn neurons with aberrant integrations in SE mice wassignificantly increased when compared with the control mice (P <0.05).Conclusion These data demonstrate the existence of aberrant integrations-hilar basal dendrites,hilar ectopic migration and mossy fiber sprouting in the DG-generated cells born 1 week before an SE insult.
ABSTRACT
Objective To determine whether the integration of immature neurons born before status epilepticus (SE)can be disrupted by an epileptogenic insult.Methods Pilocarpine was used to induce SE in mice. At week 1 before induction,BrdU or retroviral vector expressing green fluorescent protein (RV-GFP)was used to label the newly born cells in the dentate gyrus (DG).At week 8 after SE,BrdU+Map2 or BrdU+NeuN double-labeling staining was carried out to visualize hilar basal dendrite or hilar ectopic migration.Virus-transduced GFP signals were used to identify the mossy fiber sprouting from the newly generated neurons.The number of cells with aberrant integrations was compared using unpaired Student's t-test.Results The percentage of newborn neurons with aberrant dendritic morphology was (20.8±8.4)% at week 8 after SE.The percentage of BrdU+NeuN double labeled cells ectopically migrated into the hilus was (15.9 ± 7.4)%.At week 8 after SE,the chronically epileptic mice showed many GFP+ processes in the IML with the same axonal appearance and small mossy fiber bouton-like structures as those seen in the hilus.The number of newborn neurons with aberrant integrations in SE mice wassignificantly increased when compared with the control mice (P <0.05).Conclusion These data demonstrate the existence of aberrant integrations-hilar basal dendrites,hilar ectopic migration and mossy fiber sprouting in the DG-generated cells born 1 week before an SE insult.