Copolymer-1 enhances cognitive performance in young adult rats

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.

Probiotics and Prebiotics as a Therapeutic Strategy to Improve Memory in a Model of Middle-Aged Rats

“…The autoshaping program consisted of discrete trials, each composed of the presentation of the light stimulus for 8 s (conditioned stimulus, CS) followed by delivery of a 45 mg food pellet (unconditioned stimulus, US) with an inter-trial time (ITT) of 60 s. Once the animal placed its nose inside the nose-poke in response to the CS, the trial was shortened, and the light was turned off, and a food pellet (US) was immediately delivered, followed by the ITT. The response during CS was regarded as a CR, and its increase or decrease was considered as an enhancement or impairment measure of memory, respectively (Nieto-Vera et al, 2018). The autoshaping results were reported as the percentage obtained by the ratio: number of times the animal responded to the stimulus (by touching the nose poke and getting the pellets)/total number of CS (light).…”

Immunization with Neural-Derived Peptides in Neurodegenerative Diseases: A Narrative Review

“…Neuroinflammatory events have also been postulated as possible contributors to PD pathogenesis, as it has been confirmed in post-mortem studies that many of the apoptotic nigrostriatal dopaminergic neurons showed high amounts of molecules such as IL-6 and TNFα and apoptosis-related factors such as p55, Fas and caspases 1-2 [ 49 ]. Furthermore, the intermediary molecules resulting from α-Synuclein accumulation trigger innate as well as the adaptive immunity, promoting microglia activation and ROS production, disturbing synaptic function and causing neuronal degeneration and chronic neuroinflammation.…”

Copolímero-1 como terapia potencial para el deterioro cognitivo leve

“…37 Como se mencionó con anterioridad, el deterioro cognitivo se asocia con una disminución de niveles de BDNF y deterioro de la función inmunitaria. 38 Al considerar lo anterior, estudios recientes muestran que la inmunización con Cop-1 puede mejorar los niveles de BDNF en el hipocampo e inducir una mejor función cognitiva; la inmunización con Cop-1 mejora la memoria y el aprendizaje, estimula la expresión de BDNF, 10 al modular la función sináptica y la plasticidad relacionadas con la cognición y la memoria. 39 Además, dicha inmunización puede promover la migración y acumulación de linfocitos Th2 en el cerebro, permitiendo que interactúen con las células residentes y de esta manera restauren la función inmune.…”

“…Las interacciones neuroinmunes son importantes para promover la neuroplasticidad relacionada con la memoria y el apren-dizaje. 40 Ya que la inmunización con Cop-1 puede inducir neurogénesis, 35 y con ello mejora la función cognitiva, 10 entonces el tratamiento con Cop-1 puede participar de manera importante en la reducción del deterioro cognitivo.…”

“…De esta manera, Cop-1 representa una opción terapéutica potencial para mejorar la cognición. 10 En este artículo proponemos utilizar Cop-1 como un tratamiento novedoso y potencial para tratar el DCL.…”