TY - JOUR
T1 - Nitric oxide donor molsidomine promotes retrieval of object recognition memory in a model of cognitive deficit induced by 192 IgG-saporin
AU - Hernández-Melesio, M. Alejandra
AU - Alcaraz-Zubeldia, Mireya
AU - Jiménez-Capdeville, María E.
AU - Martínez-Lazcano, Juan Carlos
AU - Santoyo-Pérez, Martha E.
AU - Quevedo-Corona, Lucía
AU - Gerónimo-Olvera, Cristian
AU - Sánchez-Mendoza, Alicia
AU - Ríos, Camilo
AU - Pérez-Severiano, Francisca
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/7/2
Y1 - 2019/7/2
N2 - Nitric oxide (NO) plays a leading role in learning and memory processes. Previously, we showed its ability to modify the deleterious effect of immunotoxin 192 IgG-saporin (192-IgG-SAP) in the cholinergic system. The aim of this study was to analyze the potential of a NO donor (molsidomine, MOLS) to prevent the recognition memory deficits resulting from the septal cholinergic denervation by 192 IgG-SAP in rats. Quantification of neuronal and endothelial nitric oxide synthase (nNOS and eNOS, respectively) expression was evaluated in striatum, prefrontal cortex, and hippocampus. In addition, a choline acetyltransferase immunohistochemical analysis was performed in medial septum and assessed the effect of MOLS treatment on the spatial working memory of rats through a recognition memory test. Results showed that 192-IgG-SAP reduced the immunoreactivity of cholinergic septal neurons (41%), compared with PBS-receiving control rats (p < 0.05). Treatment with MOLS alone failed to antagonize the septal neuron population loss but prevented the progressive abnormal morphological changes of neurons. Those animals exposed to 192-IgG-SAP immunotoxin exhibited a reduction of cortical nNOS expression against the control group, whereas expression was enhanced in the 192-IgG-SAP + MOLS group. The most relevant finding was the recovering of the discrimination index exhibited by the 192-IgG-SAP + MOLS group. When compared with the rats exposed to the 192-IgG-SAP immunotoxin, they reached values similar to those observed in the PBS group. Our results show that although MOLS failed to block the cholinergic neurons loss induced by 192-IgG-SAP, it avoided the neuronal damage progression.
AB - Nitric oxide (NO) plays a leading role in learning and memory processes. Previously, we showed its ability to modify the deleterious effect of immunotoxin 192 IgG-saporin (192-IgG-SAP) in the cholinergic system. The aim of this study was to analyze the potential of a NO donor (molsidomine, MOLS) to prevent the recognition memory deficits resulting from the septal cholinergic denervation by 192 IgG-SAP in rats. Quantification of neuronal and endothelial nitric oxide synthase (nNOS and eNOS, respectively) expression was evaluated in striatum, prefrontal cortex, and hippocampus. In addition, a choline acetyltransferase immunohistochemical analysis was performed in medial septum and assessed the effect of MOLS treatment on the spatial working memory of rats through a recognition memory test. Results showed that 192-IgG-SAP reduced the immunoreactivity of cholinergic septal neurons (41%), compared with PBS-receiving control rats (p < 0.05). Treatment with MOLS alone failed to antagonize the septal neuron population loss but prevented the progressive abnormal morphological changes of neurons. Those animals exposed to 192-IgG-SAP immunotoxin exhibited a reduction of cortical nNOS expression against the control group, whereas expression was enhanced in the 192-IgG-SAP + MOLS group. The most relevant finding was the recovering of the discrimination index exhibited by the 192-IgG-SAP + MOLS group. When compared with the rats exposed to the 192-IgG-SAP immunotoxin, they reached values similar to those observed in the PBS group. Our results show that although MOLS failed to block the cholinergic neurons loss induced by 192-IgG-SAP, it avoided the neuronal damage progression.
KW - 192 IgG-saporin
KW - Cholinergic septal neurons
KW - Molsidomine
KW - Nitric oxide synthase
KW - Object recognition test
UR - http://www.scopus.com/inward/record.url?scp=85063286557&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2019.03.031
DO - 10.1016/j.bbr.2019.03.031
M3 - Artículo
C2 - 30898683
AN - SCOPUS:85063286557
SN - 0166-4328
VL - 366
SP - 108
EP - 117
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -