Antidepressant effects of creatine on amyloid β1-40 -treated mice: The role of GSK-3β/Nrf2 pathway

Progress in Neuro-psychopharmacology & Biological Psychiatry
Julia Macedo RosaAna Lúcia S Rodrigues

Abstract

Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction and neuronal lost in specific brain areas including hippocampus, resulting in memory/learning deficits and cognitive impairments. In addition, non-cognitive symptoms are reported in AD patients, such as anxiety, apathy and depressed mood. The current antidepressant drugs present reduced efficacy to improve depressive symptoms in AD patients. Here, we investigated the ability of creatine, a compound with neuroprotective and antidepressant properties, to counteract amyloid β1-40 peptide-induced depressive-like behavior in mice. Moreover, we addressed the participation of the intracellular signaling pathway mediated by glycogen synthase kinase-3β (GSK-3β)/nuclear factor erythroid-2-related factor 2 (Nrf2) in the creatine effects. Aß1-40 administration (400 pmol/mouse, i.c.v.) increased the immobility time in the tail suspension test and decreased the grooming time and increased latency to grooming in the splash test, indicative of depressive-like behavior. These impairments were attenuated by creatine (0.01 and 10 mg/kg, p.o.) and fluoxetine (10 mg/kg, p.o., positive control). No significant alterations on locomotor performance were observed in the open ...Continue Reading

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Citations

Jul 14, 2020·Artificial Cells, Nanomedicine, and Biotechnology·Tong LiuWeisheng Feng
May 23, 2020·Chronic Stress·Anderson Camargo, Ana Lúcia S Rodrigues

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