title: Intranasal Cerebrolysin Attenuates Learning and Memory Impairments in D-galactose-Induced Senescence in Mice.
abstract: Neurotrophic factors are currently being considered as pro-cognitive therapeutic approaches for management of cognitive deficits. This study aims to evaluate the effects of intranasal (i.n.) or intraperitoneal (i.p.) administration of Cerebrolysin (CBL) (as a mixture of neurotrophic factors) on the d-galactose-induced oxidative stress, apoptosis and memory as well as learning impairment in mice. For this purpose, CBL (1, 2.5, 5 ml/kg/i.p.) or (1 ml/kg/i.n.), were administrated daily in d-galactose-received (100 mg/kg/subcutaneous (s.c.)) mice model of aging for eight weeks. Spatial and recognition memories were assessed by the Morris water maze and novel object recognition tasks. Brain and blood of animals were analysed for oxidative stress biomarkers including malondialdehyde, total antioxidant capacity, glutathione peroxidase and superoxide dismutase. Apoptosis rate in the hippocampus was evaluated by TUNEL staining of brain tissue. 5 ml/kg/i.p. dose of CBL increased the locomotor activity but, 1 ml/kg/i.p. dose didn't show detectable behavioural or molecular effects on aged mice. Treatment with 2.5 ml/kg/i.p. and 1 ml/kg/i.n. doses attenuated d-galactose-impaired spatial and recognition memories. Results showed an obvious increase in the antioxidant biomarkers and decrease in the malondialdehyde levels both in the blood and brain of aged mice in 2.5 ml/kg/i.p. dose, and only in the brain in 1 ml/kg/i.n. dose of CBL. Anti-apoptotic effects also were seen in the same dose/rout of CBL administration in aged animals. This study proves the usefulness of i.n. CBL administration as a non-invasive and efficient method of drug delivery to the brain to improve aging-induced oxidative stress, apoptosis and learning as well as memory impairment.
authors.affiliation: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Pourmemar
authors.affiliation: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Majdi
authors.affiliation: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Haramshahi
authors.affiliation: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Talebi
authors.affiliation: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Pouran
authors.initials: P
authors.lastname: Karimi
authors.affiliation: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: Saeed.sadigetegad@gmail.com.
authors.forename: Saeed
authors.initials: S
authors.lastname: Sadigh-Eteghad
mesh_terms: D000281:Administration, Intranasal; D000375:Aging / Q000187:drug effects*; D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D005690:Galactose / Q000633:toxicity; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D018696:Neuroprotective Agents; C006952:cerebrolysin; D005690:Galactose
keywords: Cerebrolysin; D-galactose; Intranasal; Learning; Memory; Senescence