Journal Article Epublish
PubMed: 42399524 DOI: 10.1007/s12640-026-00807-0
EGF and GHRP6 Co-Administration Attenuates Cognitive Decline in Preclinical Models: Behavioral and Molecular Evidences.
Neurotox Res 44(4)
Authors: Daniela Risco-Acevedo, Nelvys Subirós-Martínez, Hanlet Camacho-Rodríguez, Jeney Ramírez-Sánchez, Yaima Rodríguez-Virulich, Ana Yansi Etchegoyen-Amoros, Wendy Hernández-Estrada, Maylin Wong-Guerra, Yanay Montano-Peguero, Thalia Estrada-Olivares, Dasha Fuentes-Morales, Daniel Palenzuela-Gardón, Héctor Pérez-Saad, Yanier Núñez-Figueredo, Li Wen, Gerardo E Guillén-Nieto, Diana García-Del-Barco-Herrera
Affiliations
- Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), 31th Avenue 15802, Playa, Havana, 11600, Cuba.
- Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), 31th Avenue 15802, Playa, Havana, 11600, Cuba.
- Department of Biology, Faculty of Chemistry and Biology, Universidad de Santiago de Chile (USACH), Santiago, Alameda, 3363, Chile.
- Faculty of Chemical and Pharmaceutical Sciences, Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santos Dumont 964, Santiago, Chile.
- National Center for Laboratory Animal Breeding (CENPALAB), 3rd Street 40759 between 6th and Carretera Tirabeque, La Union District, Boyeros, Havana, 10800, Cuba.
- Laboratory of Experimental Neuropharmacology, Center for Drug Research and Development (CIDEM), 26Th Avenue 1605, Havana, 10600, Cuba.
- China-Cuba Biotechnology Joint Innovation Center (CCBJIC), Lengshuitan District, Yongzhou City, Hunan, 425000, China.
- Biomedical Research Division, Center for Genetic Engineering and Biotechnology (CIGB), 31th Avenue 15802, Playa, Havana, 11600, Cuba.
- China-Cuba Biotechnology Joint Innovation Center (CCBJIC), Lengshuitan District, Yongzhou City, Hunan, 425000, China.
Abstract
Cognitive decline is a hallmark of neurodegenerative diseases. The complex pathophysiology of these diseases has limited the efficacy of current therapies. The co-administration of epidermal growth factor (EGF) and growth hormone-releasing peptide 6 (GHRP6) emerges as a promising neuroprotective candidate. The present study evaluated the therapeutic potential of this combination in two preclinical models of cognitive impairment: (i) age-related decline and (ii) impairment induced by intracerebroventricular administration of streptozotocin (STZ). In both experiments, C57BL/6 mice were used and distributed into three experimental groups, each comprising 14-15 animals per group. Cognitive and motor function was assessed through gait pattern, Y-maze and novel object recognition tests. Differential gene expression was analyzed using qPCR. Both models reproduced hallmark features of cognitive decline, including deficits in working and spatial memory and changes in the expression of genes associated with oxidative stress, neuroinflammation and synaptic plasticity. In aged animals, EGF + GHRP6 treatment increased step length (p = 0.04). In the forced alternation Y-maze test, aged-EGF + GHRP6 animals made more visits to the novel arm than to the familiar arm 1 (p = 0.001) or to the familiar arm 2 (p = 0.04). Cognitive benefits were also observed in the STZ-induced model. STZ-EGF + GHRP6 group exhibited an alternation percentage higher than the STZ-vehicle group (p = 0.03). Moreover, EGF + GHRP6 treatment significantly increased the expression of genes associated with antioxidant defense (Hmox1), synaptic plasticity (Creb1), and oligodendrocyte differentiation (Olig1) while concurrently reducing the expression of Nfkb1. These findings highlight the therapeutic potential of EGF + GHRP6 co-administration as a neuroprotective strategy to mitigate neurodegeneration and preserve cognitive function.
MeSH
Genes, Growth, Neuronal Plasticity, Cognitive Dysfunction, Aged, Therapeutics