Synergistic neuroprotective action of prolactin and 17β-estradiol on kainic acid-induced hippocampal injury and long-term memory deficit in ovariectomized rats.

Abstract

Abstract Purpose The neuroprotective actions of the ovarian hormone 17β-estradiol (E2) against different brain lesions have been continuously confirmed in a variety of models including kainic acid (KA) lesions. In the same line, the pituitary hormone prolactin (PRL), traditionally associated to lactogenesis, has recently been linked to a great diversity of functions, including neurogenesis, neuroprotection, and cognitive processes. While the mechanisms of actions of E2 regarding its neuroprotective and behavioral effects have been extensively explored, the molecular mechanisms of PRL related to these roles remain under investigation. The aim of the current study was to explore if the simultaneous administration of PRL and a low dose of E2 prevents the KA-induced cognitive deficit and if this action is associated to changes in hippocampal neuronal density. Methods Ovariectomized (OVX) rats were treated with saline, PRL and/or E2 in the presence or absence of KA. Neuroprotection was assessed by Nissl staining and neuron counting. Evaluation of memory was carried out by means of the novel object recognition test (NOR). Results These findings indicate that both PRL and E2 prevent short- and long-term memory deficits in lesioned animals. In addition, both hormones exert neuroprotection against KA-induced excitotoxicity in the hippocampus. Interestingly, the combined hormonal treatment was superior at improving the behavioral performance of rats in the NOR and neuronal survival than either treatment administered separately. Conclusion Taken together, these results suggest that these hormones act in different ways at the hippocampus to produce their behavioral, proliferative, and neuroprotective effects.