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Abstract: 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho) (1μM) enhanced long-term depression (LTD), a synaptic plasticity relevant to learning and memory, in the CA1 region of rat hippocampal slices, where expression of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluR1 on the plasma membrane was decreased. In the water maze test, oral administration with POPhtCho (5mg/kg) significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine (1mg/kg), while the acquisition latency was not affected. For humans with mild cognitive impairment and dementia (average of Mini Mental State Examination score, 18), oral intake with POPhtCho (300mg/day, once after breakfast) everyday raised the score to over 20, corresponding to normal cognitive functions, throughout 6 months after intake. The results of the present study, thus, indicate that POPhtCho could ameliorate cognitive disorders, possibly by enhancing LTD. [Copyright &y& Elsevier]

In a whole-cell patch-clamp configuration, currents through N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor channels were monitored in cultured rat hippocampal neurons, and those currents were depressed to 25 and 28% of basal levels, respectively, by 3-min treatment with tunicamycin (10 μM), an inhibitor of protein N-glycosylation. Tunicamycin (10 μM) reduced amplitude of population spikes elicited in the dentate gyrus of rat hippocampal slices, reaching 78% of basal levels 60 min after the beginning of treatment, and long-term potentiation (LTP) of the perforant path was never induced in the presence of tunicamycin. Tunicamycin, thus, appears to serve as a modulator for NMDA and AMPA receptors, regardless of N-glycosylation, thereby inhibiting neurotransmission and LTP in the dentate gyrus. [Copyright &y& Elsevier]

The present study investigated the effects of amyloid-β peptides on nicotinic ACh receptors (Torpedo, α4β2, and α7 receptors) and AMPA receptors expressed in Xenopus oocytes by monitoring whole-cell membrane currents. Ten-minutes treatment with amyloid-β1–42 (1 μM) inhibited Torpedo ACh receptor currents, reaching 53% of original levels 30 min after treatment. Amyloid-β1–40 inhibited the currents in a dose-dependent manner (0.1–10 μM) during treatment, gradually reversing after treatment. Amyloid-β1–40 and amyloid-β1–42 (0.1 μM) depressed α4β2 receptor currents to each 69% and 62% of original levels at 10-min treatment and lesser depression was obtained with α7 receptors. Amyloid-β1–42 (0.1 μM) did not significantly inhibit AMPA receptor currents, but amyloid-β1–40 (0.1 μM) potentiated the currents to 145–191% of original levels. Amyloid-β peptides, thus, exert their diverse actions on nicotinic ACh receptors and AMPA receptors, and the inhibitory actions on nicotinic ACh receptors may account for the deterioration of learning and memory in Alzheimer''s disease. [Copyright &y& Elsevier]