Cerebrolysin enhances the expression of the synaptogenic protein LRRTM4 in the hippocampus and improves learning and memory in senescent rats

Aging reduces the efficiency of the organs and systems, including the cognitive functions. Brain aging is related to a decrease in the vascularity, neurogenesis, and synaptic plasticity. Cerebrolysin, a peptide and amino acid preparation, has been shown to improve the cognitive performance in animal models of Alzheimer's disease. Similarly, the leucine-rich repeat transmembrane 4 protein exhibits a strong synaptogenic activity in the hippocampal synapses. The aim of this study was to evaluate the effect of the cerebrolysin treatment on the learning and memory abilities, sensorimotor functions, and the leucine-rich repeat transmembrane 4 protein expression in the brain of 15-month-old rats. Cerebrolysin (1076 mg/kg) or vehicle was administered to Wistar rats intraperitoneally for 4 weeks. After the treatments, learning and memory were tested using the Barnes maze test, and the acoustic startle response, and its pre-pulse inhibition and habituation were measured. Finally, the leucine-rich repeat transmembrane 4 expression was measured in the brainstem, striatum, and hippocampus using a Western-blot assay. The 15-month-old vehicle-treated rats showed impairments in the habituation of the acoustic startle response and in learning and memory when compared to 3-month-old rats. These impairments were attenuated by the subchronic cerebrolysin treatment. The leucine-rich repeat transmembrane 4 protein expression was lower in the old vehicle-treated rats than in the young rats; the cerebrolysin treatment attenuated that decrease in the old rats. The leucine-rich repeat transmembrane 4 protein was not expressed in striatum or brainstem. These results suggest that the subchronic cerebrolysin treatment enhances the learning and memory abilities in aging by increasing the expression of the leucine-rich repeat transmembrane 4 protein in the hippocampus.