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Long-term potentiation (LTP) was monitored from the CA1 region of the intact rat hippocampus by delivering high frequency stimulation (HFS) to the Schaffer collateral commissural pathway. Intraventricular injection with mutant amyloid beta(1-42) peptide lacking glutamate-22 (Abeta(1-42)E22Delta), favoring oligomerization, 10 min prior to HFS, inhibited expression of LTP, with the potency more than wild-type amyloid beta(1-42) peptide. Intraperitoneal injection with the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) 70 min prior to HFS neutralized mutant Abeta(1-42)E22Delta peptide-induced LTP inhibition. In the water maze test, continuous intraventricular injection with mutant Abeta(1-42)E22Delta peptide for 14 days prolonged the acquisition latency as compared with that for control, with the potency similar to wild-type Abeta(1-42) peptide, and intraperitoneal injection with DCP-LA shortened the prolonged latency to control levels. The results of the present study indicate that DCP-LA neutralizes mutant Abeta(1-42)E22Delta peptide-induced impairment of LTP and spatial learning.

Expression of Schaffer collateral-CA1 long-term potentiation (LTP) and long-term depression (LTD) was not affected in hippocampal slices from wild-type mice pretreated with lipopolysaccharide (0.25mg/kg, i.p.), to increase interleukin-18 (IL-18) concentrations in the brain. For IL-18 knock-out (IL-18 KO) mice, the LTP was still expressed, the extent being similar to that for wild-type mice. In the open-field test to assess motor activity, rearing activity for IL-18 KO mice was significantly suppressed as compared with that for wild-type mice, without significant difference in the locomotion activity between two groups. In the passive avoidance test to assess fear memory, the retention latency for IL-18 KO mice was much shorter than for wild-type mice, without significant difference in the acquisition latency between two groups. In the water maze test, the acquisition latency for IL-18 KO mice significantly prolonged as compared with that for wild-type mice, without significant difference in the retention latency between two groups. For IL-18 KO mice, intraventricular injection with IL-18 for 4 days (total, 240 fg) prior to water maze task shortened the prolonged acquisition latency, reaching a level similar to that for wild-type mice. The results of the present study, thus, suggest that IL-18 is a critical regulator for exploratory activity, fear memory, and spatial learning.

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho) (1 microM) 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 alpha-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 (5 mg/kg) significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine (1 mg/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 (300 mg/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.

The present study examined the effects of the proinflammatory cytokine interleukin-18 (IL-18) on mouse hippocampal synaptic transmission. IL-18 (100 ng/ml) significantly increased amplitude and frequency of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated miniature excitatory postsynaptic currents (AMPA-mEPSCs), that are monitored from CA1 pyramidal neurons of mouse hippocampal slices. IL-18 (100 ng/ml) enhanced slope of basal field excitatory postsynaptic potentials (fEPSPs) that are recorded from the CA1 region of mouse hippocampal slices. There was no significant difference in the expression of Schaffer collateral/CA1 long-term potentiation (LTP) between in the presence and absence of IL-18, although IL-18 tended to inhibit saturation levels of the potentiation induced by tetanic stimulation in a dose-dependent manner at concentrations ranged from 10 ng/ml to 1 microg/ml. Paired-pulse facilitation in the presence of IL-18 (100 ng/ml) was not influenced after tetanic stimulation, while that in the absence of IL-18 was depressed. The results of the present study, thus, suggest that IL-18 stimulates synaptically released glutamate and enhances postsynaptic AMPA receptor responses in CA1 pyramidal neurons of mouse hippocampal slices, thereby facilitating basal hippocampal synaptic transmission without affecting the LTP., (Copyright 2004 Elsevier B.V.)

In a whole-cell patch-clamp configuration, currents through N-methyl-D-aspartate (NMDA) and alpha-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 microM), an inhibitor of protein N-glycosylation. Tunicamycin (10 microM) 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.

The present study investigated the effects of (-)-epigallocatechin gallate (EGCG), which is the major component of polyphenol in green tea, on nitric oxide (NO) stress-induced neuronal damage, by monitoring NO mobilizations in the intact rat hippocampus and assaying the viability of cultured rat hippocampal neurons. A 10-min ischemia increased NO (NO(3)(-)/NO(2)(-)) concentrations in the intact rat hippocampus, while EGCG (50 mg/kg i.p.) inhibited the increase by 77% without affecting hippocampal blood flow. The NO donor, sodium nitroprusside (SNP; 50 microM), produced NO (NO(3)(-)/NO(2)(-)), while EGCG inhibited it in a dose-dependent manner at concentrations ranging from 50 to 200 microM. Treatment with SNP (100 microM) reduced the viability of cultured rat hippocampal neurons to 22% of control levels, while EGCG caused it to recover to 51% for 10 microM, 73% for 20 microM, and 70% for 50 microM. Taken together, it appears that EGCG could protect against ischemic neuronal damage by deoxidizing peroxynitrate/peroxynitrite, which is converted to NO radical or hydroxy radical., (Copyright 2002 Elsevier Science B.V.)