Status epilepticus induces region-specific changes in dendritic spines, dendritic length and TrkB protein content of rat brain cortex.
Induction of status epilepticus (SE) with kainic acid results in a large reorganization of neuronal brain circuits, a phenomenon that has been studied primarily in the hippocampus. The neurotrophin BDNF, by acting through its receptor TrkB, has been implicated in such reorganization. In the present work we investigated, by Western blot and immunohistochemistry, whether regional changes of TrkB expression within the rat brain cortex are correlated with altered neuronal morphology and/or with apoptotic cell death. We found that the full-length TrkB protein decreased within the cortex when measured 24 h to 1 week after induction of SE. Analysis by immunohistochemistry revealed that TrkB staining diminished within layer V of the retrosplenial granular b (RSGb) and motor cortices, but not within the auditory cortex. In layer II/III, differential changes were also observed: TrkB decreased in the motor cortex, did not change within the RSGb but increased within the auditory cortex. Reduced TrkB was associated with dendritic atrophy and decreased spine density in pyramidal neurons within layer V of the RSGb. No correlation was observed between regional and cellular changes of TrkB protein and apoptosis, measured by the TdT-mediated dUTP nick end labeling (TUNEL) method. The global decrease of TrkB within the neocortex and the associated dendritic atrophy may counteract seizure propagation in the epileptic brain but may also underlie cognitive impairment after seizures.
Ampuero
Estíbaliz
E
Neuroscience Laboratory, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
Dagnino-Subiabre
Alexies
A
Sandoval
Rodrigo
R
Zepeda-Carreño
Rodrigo
R
Sandoval
Soledad
S
Viedma
Alejandra
A
Aboitiz
Francisco
F
Orrego
Fernando
F
Wyneken
Ursula
U
D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology*; D049229:Dendritic Spines / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling / Q000379:methods; D007608:Kainic Acid; D008297:Male; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism*; D016622:Silver Staining / Q000379:methods; D018709:Statistics, Nonparametric; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors
D020813:Receptor, trkB; D007608:Kainic Acid