2-3-5-4--tetrahydroxystilbene-2-o-glucopyranoside and Memory-Disorders

Memory impairment can be progressive in neurodegenerative diseases, and physiological ageing or brain injury, mitochondrial dysfunction and oxidative stress are critical components of these issues. An early clinical study has demonstrated cognitive improvement during erythropoietin treatment in patients with chronic renal failure. As erythropoietin cannot freely cross the blood-brain barrier, we tested EH-201 (2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside, also known as TSG), a low MW inducer of erythropoietin, for its therapeutic effects on memory impairment in models of neurodegenerative diseases, physiological ageing or brain injury.. The effects of EH-201 were investigated in astrocytes and PC12 neuronal-like cells. In vivo, we used sleep-deprived (SD) mice as a stress model, amyloid-β (Aβ)-injected mice as a physiological ageing model and kainic acid (KA)-injected mice as a brain damage model to assess the therapeutic effects of EH-201.. EH-201 induced expression of erythropoietin, PPAR-γ coactivator 1α (PGC-1α) and haemoglobin in astrocytes and PC12 neuronal-like cells. In vivo, EH-201 treatment restored memory impairment, as assessed by the passive avoidance test, in SD, Aβ and KA mouse models. In the hippocampus of mice given EH-201 in their diet, levels of erythropoietin, PGC-1α and haemoglobin were increased. The induction of endogenous erythropoietin in neuronal cells by inducers such as EH-201 might be a therapeutic strategy for memory impairment in neurodegenerative disease, physiological ageing or traumatic brain injury.

Topics: Animals; Astrocytes; Cells, Cultured; Disease Models, Animal; Erythropoietin; Female; Glucosides; Hemoglobins; Hydrogen Peroxide; Kainic Acid; Male; Memory Disorders; Mice, Inbred C57BL; Mitochondria; Neuroprotective Agents; PC12 Cells; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Rats; Reactive Oxygen Species; Stilbenes; Succinate Dehydrogenase; Transcription Factors

To investigate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) on the memory and movement functions and its mechanisms related to synapses and α-synuclein in aged mice.. The memory ability of mice was detected by step-through passive avoidance task. The movement function was measured by the pole test and rotarod test. Transmission electron microscopy was used to observe the synaptic ultrastructure. Western blotting was applied to measure the expression of synapse-related proteins and α-synuclein.. Intragastrical administration of TSG for 3 months significantly improved the memory and movement functions in aged mice. TSG treatment obviously protected the synaptic ultrastructure and increased the number of synaptic connections in the hippocampal CA1 region and striatum; enhanced the expression of synaptophysin, phosphorylated synapsin I and postsynaptic density protein 95 (PSD95), elevated phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMKII) expression, and inhibited the overexpression and aggregation of α-synuclein in the hippocampus, striatum and cerebral cortex of aged mice.. TSG improved the memory and movement functions in aged mice through protecting synapses and inhibiting α-synuclein overexpression and aggregation in multiple brain regions. The results suggest that TSG may be beneficial to the treatment of ageing-related neurodegenerative diseases.

Topics: Aging; alpha-Synuclein; Animals; Avoidance Learning; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cerebral Cortex; Corpus Striatum; Female; Glucosides; Hippocampus; Memory; Memory Disorders; Mice, Inbred C57BL; Motor Activity; Movement Disorders; Neuroprotective Agents; Nootropic Agents; Protein Aggregates; Stilbenes; Synapses; Treatment Outcome