Reversal learning impairment and alterations in the prefrontal cortex and the hippocampus in a model of portosystemic hepatic encephalopathy.
Patients with liver dysfunction often suffer from hepatic encephalopathy (HE), a neurological complication that affects attention and memory. Various experimental animal models have been used to study HE, the most frequently used being the portocaval shunt (PCS). In order to determine brain substrates of cognitive impairment in this model, we assessed reversal learning and c-Fos expression in a rat model of portosystemic derivation. PCS and sham-operated rats (SHAM) were tested for reversal learning. Brains were processed for c-Fos immunocytochemistry. The total number of c-Fos positive nuclei was quantified in the prefrontal cortex and hippocampus. The spatial reference memory task showed no differences between groups in escape latencies. The no-platform probe test showed that both the PCS and the SHAM learned the location of platform. However, the PCS group perseverated in the old target during reversal. The PCS group presented less c-Fos- positive cells in prelimbic cortex, CA1 and dentate gyrus of the dorsal hippocampus than SHAM. Overall, these results suggest that this specific model of portosystemic hepatic encephalopathy produces reversal learning impairment that could be linked to dysfunction in neuronal activity in the prefrontal cortex and hippocampus.
Laboratorio de Neurociencias, Departamento de Psicología, Universidad de Oviedo, Spain. mendezlmarta@uniovi.es
Marta
M
Méndez
Magdalena
M
Méndez-López
Laudino
L
López
Azucena
A
Begega
María Angeles
MA
Aller
Jaime
J
Arias
Jorge L
JL
Arias
D000818:Animals; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008568:Memory / Q000502:physiology; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D012193:Reversal Learning / Q000502:physiology*; D013028:Space Perception / Q000502:physiology
D016760:Proto-Oncogene Proteins c-fos