Abstract
Cognitive impairment is a dysfunction observed as a sequel of various neurodegenerative diseases, as well as a concomitant element in the elderly stages of life. In clinical settings, this malfunction is identified as mild cognitive impairment. Previous studies have suggested that cognitive impairment could be the result of a reduction in the expression of brain-derived neurotrophic factor (BDNF) and/or immune dysfunction. Copolymer-1 (Cop-1) is an FDA-approved synthetic peptide capable of inducing the activation of Th2/3 cells, which are able to release BDNF, as well as to migrate and accumulate in the brain. In this study, we evaluated the effect of Cop-1 immunization on improvement of cognition in adult rats. For this purpose, we performed four experiments. We evaluated the effect of Cop-1 immunization on learning/memory using the Morris water maze for spatial memory and autoshaping for associative memory in 3- or 6-month-old rats. BDNF concentrations at the hippocampus were determined by ELISA. Cop-1 immunization induced a significant improvement of spatial memory and associative memory in 6-month-old rats. Likewise, Cop-1 improved spatial memory and associative memory when animals were immunized at 3 months and evaluated at 6 months old. Additionally, Cop-1 induced a significant increase in BDNF levels at the hippocampus. To our knowledge, the present investigation reports the first instance of Cop-1 treatment enhancing cognitive function in normal young adult rats, suggesting that Cop-1 may be a practical therapeutic strategy potentially useful for age- or disease-related cognitive impairment.
Highlights
Numerous studies have shown that traumatic brain injury, stroke, or even spinal cord injury induce cognitive impairment (CI) [1,2,3]
CI has been found to result from diverse factors, the pathophysiological mechanisms behind it have been associated to a reduction of brain-derived neurotrophic factor (BDNF) levels and/or a deficient immune function [8,25]
LTP is divided into two phases: a) induction of LTP or early phase LTP (E-LTP) and b) maintenance of LTP, or late phase LTP (L-LTP)
Summary
Numerous studies have shown that traumatic brain injury, stroke, or even spinal cord injury induce cognitive impairment (CI) [1,2,3]. It has been reported that 10–20% of humans aged 65 years and older may present CI, a major public health concern with a rapidly increasing incidence worldwide [4]. In order to address this scenario, clinicians face the challenge of identifying clinically significant cognitive changes for the diagnosis of CI [5]. In this regard, longitudinal studies have demonstrated multiple patterns of cognitive change with. Copolymer-1 improves cognition decision to publish, or preparation of the manuscript
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