Title : Novel effects of glucosamine on animal learning and memory
Abstract:
Learning and memory functions are closely linked and significantly influence quality of life. The degeneration or loss of these functions due to diseases or aging, such as Alzheimer's disease, has become a major health concern. Research has shown that fibroblast growth factor 21 (FGF21) plays a vital role in both metabolism and cognitive functions. Glucosamine (GLN) is well known for its wide range of beneficial effects, and our previous studies have demonstrated its positive impact on cognitive performance in animals, accompanied by an increase in brain-derived neurotrophic factor (BDNF) levels. In our recent studies, which included both in vivo and in vitro experiments, we investigated the effects of GLN on mice fed either a normal or high- fat diet, as well as on mouse HT22 hippocampal cells, STHdhQ7/Q7 striatal cells, and rat primary cortical neurons. The findings clearly showed that GLN improves learning and memory in mice, and notably, it also induced FGF21 production in the hippocampus, cortex, and striatum, as well as in HT22 cells, STHdhQ7/Q7 cells, and cortical neurons. When animals were administered GLN together with an FGF21 receptor inhibitor (PD173074), the GLN-induced enhancement of learning and memory functions, as well as FGF21 production in the hippocampus, were significantly reduced. Given that Alzheimer's disease is a leading cause of dementia, characterized by age-related neurodegeneration and amyloid β (Aβ) protein aggregation, which leads to synaptic damage, protein loss, neurofibrillary tangles, neuroinflammation, and cell apoptosis, we also aimed to determine whether GLN affects the expression of genes related to neuroplasticity. In the hippocampus and cortex from GLN-injected mice, GLN increased the expression of neuroplasticity markers such as synaptophysin (SYP), postsynaptic density 95 (PSD-95), Densin-180, and growth-associated protein 43 (GAP-43) at both the mRNA and protein levels, along with BDNF and FGF21. Similarly, in HT22 cells and rat primary cortical neurons treated with GLN, protein levels of SYP, PSD-95, Densin-180, and GAP-43 were also upregulated, along with BDNF and FGF21. Overall, our past and current studies on GLN have underscored its potential in enhancing learning and memory functions and may play a role in protecting against Aβ-induced cellular damage. The molecular mechanisms underlying these effects warrant further in-depth investigation.
