Synaptic Plasticity-related Proteins Research Articles

Dopamine D1 but not D3 receptor is critical for spatial learning and related signaling in the hippocampus

Experimental evidence suggests the involvement of the brain dopaminergic system in learning and memory processes, although the associated molecular mechanism has yet to be fully characterized. Memory formation occurs via a number of signaling pathways associated with activation of many synaptic plasticity-related proteins, including the N-Methyl-d-aspartic acid (NMDA) receptor, Ca2+/calmodulin-dependent protein kinase II (CaMKII), mitogen-activated protein kinases (MAPKs) and the cAMP-response element binding protein (CREB). To evaluate the roles of dopamine D1 and D3 receptors in spatial learning and memory and underlying molecular events, we have used genetically modified mice carrying either the D1 or D3 receptor gene mutations to explore the intracellular signaling pathways using Morris water maze (MWM) tasks. We show that D1 receptor mutant mice do not acquire spatial memory and do not show hippocampal activation of extracellular signal-regulated kinase (ERK) compared to wild-type mice. D3 receptor mutant mice exhibit apparent normal learning abilities in the MWM test and normal activation of MAPK signaling. Furthermore, activation of the NMDA receptor R1 subunit (NR1), CaMKII and CREB in the hippocampus is also significantly lower in D1 receptor mutant mice compared to wild-type and D3 receptor mutant mice. These results suggest that dopamine D1 but not D3 receptor is critical for spatial learning. D1 receptor-mediated signaling, associated with activation of NR1, CaMKII, ERK and CREB, is highly involved in the encoding of spatial learning and memory.

Long-term green tea catechin administration prevents spatial learning and memory impairment in senescence-accelerated mouse prone-8 mice by decreasing Aβ 1-42 oligomers and upregulating synaptic plasticity–related proteins in the hippocampus

The senescence-accelerated mouse prone-8 (SAMP8) is characterized by early onset of learning and memory deficits along with spontaneous overproduction of soluble β-amyloid peptide (Aβ) in the brain. In our study, 4 month old male SAMP8 mice were orally administered 0.05% and 0.1% green tea catechins (GTC, w/v) in drinking water for 6 months. We found that a supplementation with 0.05% or 0.1% GTC prevented spatial learning and memory impairments of mice in the Morris water maze. Better performance of GTC-treated mice was associated with decreased levels of Aβ 1-42 oligomers in the hippocampus. The activity of the protein kinase A/cAMP-response element binding protein (PKA/CREB) pathway, one of the molecular targets of Aβ oligomers which is crucial for late long-term potentiation and long-term memory formation, was significantly increased after GTC administration. We also found that chronic 0.05% or 0.1% GTC consumption prevented the reductions of three representative proteins of synaptic function and synaptic structure, including brain-derived neurotrophic factor(BDNF), post-synaptic density protein-95 (PSD95) and Ca 2+/calmodulin-dependent protein kinase II (CaMKII). These results demonstrated that long-term 0.05% or 0.1% green tea catechin administration may prevent spatial learning and memory decline of SAMP8 mice by decreasing Aβ 1-42 oligomers and upregulating synaptic plasticity–related proteins in the hippocampus.

Long-term ginsenoside administration prevents memory impairment in aged C57BL/6J mice by up-regulating the synaptic plasticity-related proteins in hippocampus

Memory impairment is considered to be one of the most prominent consequences of aging. Deterioration of memory begins in advance of old age in animals, including humans. Thus, it is extremely important to prevent memory decline for increasing healthy aging. Ginsenoside, the effective ingredient of ginseng, has been reported to have a neuron beneficial effect, but the preventive role on memory impairment and the underlying mechanisms have not been well determined. In the present study, C57BL/6J mice aged 12 months were chronically treated with ginsenoside 100 mg/kg per day for 8 months. Placebo-treated aged mice, young and adult ones (4- and 8-month-old, respectively) were used as controls. The efficacious effect of ginsenoside was manifested in the amelioration of memory impairment in aged mice by Morris water maze and step-down tests. Compared with aged control group, the plasticity-related proteins including phospho-N-methyl- d-aspartate receptor1 (NMDAR1), phospho-calcium–calmodulin dependent kinase II (CaMK II), phospho-PKA catalytic β subunit (PKA Cβ), phospho-cAMP-response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) in hippocampus significantly increased in ginsenoside treated group. These findings suggest that ginsenoside is effective on the prevention of age-related memory impairment, and the up-regulation of plasticity-related proteins in hippocampus may be one of the mechanisms.