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25–35-Induced Depression of Long-Term Potentiation in Area CA1 In Vivo and In Vitro Is Attenuated by Verapamil
Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Earlsfort Terrace, Dublin 2, Ireland
Submitted 31 October 2002; accepted in final form 22 January 2003
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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25–35 and/or intraperitoneal (ip) application of the L-type calcium channel (VDCC) blockers verapamil or diltiazem were examined in vivo. To by-pass possible systemic actions of these agents, their effects on long-term potentiation (LTP) in the CA1 region of the in vitro hippocampal slice preparation were also examined. Application of A25–35 (10 nmol in 5 µl, icv) significantly impaired LTP in vivo, as did IP injection of verapamil (1 or 10 mg/kg) or diltiazem (1 or 10 mg/kg). In the in vitro slice preparation, LTP was also depressed by prior application of A25–35 (500 nmol), verapamil (20 µM), or diltiazem (50 µM). Combined application of A25–35 and verapamil in either the in vivo or in vitro preparation resulted in a significant reversal of the LTP depression observed in the presence of either agent alone. However, co-application of diltiazem and A25–35 failed to attenuate the depression of LTP observed in the presence of either agent alone in vivo or in vitro. Since LTP is a cellular correlate of memory and A is known to be involved in Alzheimer's disease (AD), these results indicate that verapamil, a phenylalkylamine, may be useful in the treatment of cognitive deficits associated with AD. |
INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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) is recognized as an early (Lippa et al. 1998
) and critical event in the pathogenesis of Alzheimer's disease (AD) (Selkoe 1997). Amyloid deposits are found in cortical regions including the hippocampus, an area known to play a role in memory processing. A peptides have been shown to be neurotoxic in cultured cells (Yankner et al. 1990) and can lead to apoptosis in cultured hippocampal (Mattson et al. 1998) and cortical neurons (Yan et al. 1999). A has also been shown to cause disruption of calcium homeostasis. A1–40 can enhance calcium influx in rat cortical synaptosomes and cultured neurons through L- and N-type voltage-dependent calcium channels (VDCCs) (MacManus et al. 2000) and through L-type VDCCs in PC12 cells (Green and Peers 2001). Indirect activation of L-type VDCCs by A25–35 has also been reported via activation of mitogen activated protein (MAP) kinases (Ekinci et al. 1999) or generation of free radicals (Ueda et al. 1997). Postmortem analysis of the hippocampus of AD patients has revealed an increase in the density of L-type VDCCs in both the dentate gyrus and area CA1 compared with aged-matched controls (Coon et al. 1999). These findings suggest that L-type VDCCs may play a role in the pathogenesis of AD. A peptides have been shown to impair hippocampal synaptic plasticity in the form of long-term potentiation (LTP) in vitro and in vivo (Chen et al. 2000; Freir and Herron 2003; Freir et al. 2001). In addition, studies have shown a correlation between impaired synaptic plasticity and memory deficits following the generation of A aggregates in the rat hippocampus (Stephan et al. 2001).
Here we have investigated whether the depression of hippocampal LTP reported previously (Chen et al. 2000; Freir and Herron 2003; Freir et al. 2001) may be linked to a disruption of postsynaptic calcium influx, a critical event in LTP induction (Malenka et al. 1988). We therefore examined the effect of reducing the activity of L-type VDCCs via application of VDCC blockers in the presence of A25–35 in vivo and in vitro. Part of this work has been presented previously in abstract form (Costello and Herron 2002; Freir and Herron 2001).
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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All experiments in vivo were performed in accordance with guidelines and under license from the Department of Health, Ireland (86/609/EEC). Male Wistar rats, 175–200 g (8–10 wk old) were surgically prepared for acute recordings. Briefly, rats were anesthetized with an ip injection of 1.5 g/kg urethane (ethyl carbamate), and supplementary injections (0.2–0.5 g/kg) were given when necessary to ensure full anesthesia. Deep body temperature was recorded throughout the experiment, and heating pads (Braintree Scientific) were used to maintain the temperature of the animals at 36.5 ± 0.5°C. Small holes were drilled in the skull at the positions of the reference, stimulating, and recording electrodes. Additionally, in some experiments, a separate hole was drilled to introduce a guide cannula for icv injection of drug/vehicle. Animals were placed in a stereotactic frame for recording. The recording electrode was positioned in the stratum radiatum of area CA1 (3 mm posterior, 2 mm lateral to bregma). A bipolar electrode was placed in the Schaffer-collateral/commissural pathway distal to the recording electrode (4 mm posterior, 3 mm lateral to bregma). The cannula was positioned above the lateral ventricle in the opposite hemisphere to that of the electrodes (1 mm posterior, 1.2 mm lateral to bregma).
Electrophysiological recordings
Stimulating (bi-polar stainless steel; 0.125 mm diam) and recording electrodes (mono-polar stainless steel; 0.125 mm diam) obtained from Plastics One were lowered through the cortex and into area CA1 of the hippocampus using both physiological and stereotactic indicators. Test stimuli were delivered to the Schaffer-collateral/commissural pathway every 30 s (0.033 Hz). Electrodes were positioned to record a maximal field excitatory postsynaptic potential (EPSP). Baseline EPSPs were recorded at 35–40% of maximal response. LTP was induced using a high-frequency stimulus protocol (HFS; 3 x 10 trains of 10 stimuli at 200 Hz) at a stimulus intensity that evoked a field EPSP of approximately 80% of maximum response. Field EPSPs were evoked in the CA1 region using low-frequency stimulation (0.033 Hz.). Extracellular field potentials were amplified (x10), filtered at 5 kHz, digitized, and recorded using the MacLab software acquisition system. Baseline recordings were taken for 
30 min prior to injection of drug/vehicle to ensure a steady-state response. Following injection of drug/vehicle, baseline recordings were monitored for a further period of1hto monitor normal synaptic transmission. At a time of 1 h postinjection, a series of HFS were delivered to induce a potentiation of the synaptic response. Low-frequency stimulation was then used to evoke EPSPs for a further period of 1 h to record any changes in the synaptic response. Data points displayed on graphs are an average of four consecutive recordings.
Drug application
A25–35 (10 nmol in 5 µl distilled water) was injected icv (over a period of 2–3 min) using a microsyringe (Hamilton) 1 h prior to HFS. Rats were injected ip with diltiazem (1 or 10 mg/kg in 0.5 ml distilled water) or verapamil (1 or 10 mg/kg in 0.5 ml distilled water) 1 h prior to high-frequency stimulation. In experiments involving the co-application of A25–35 with verapamil or diltiazem, both drugs were injected 1 h pretetanus.
Hippocampal slice preparation
Male Wistar rats, weighing 50–100 g (4–6 wk old) were decapitated under anesthesia. The brains were rapidly removed and immersed in chilled, oxygenated artificial cerebrospinal fluid (ACSF). Brains were dissected, and transverse slices, 350 µm in thickness, were cut using a vibrotome (Campden Instruments). The slices were transferred to a holding chamber and incubated at room temperature in oxygenated ACSF for 1 h. The ACSF was composed of (in mM) 120 NaCl, 2.5 KCl, 2.0 MgSO4 2.0 CaCl2, 26 NaCO3, 1.25 NaH2PO4, and 10 D-glucose and was oxygenated with 95%O2-5%CO2. Slices were transferred to a submerged recording chamber, superfused with oxygenated ACSF at a rate of 7 ml/min, and maintained at a temperature of 29–30°C.
Electrophysiological recording
Field EPSPs (fEPSPs) were evoked using stimulating (approximately 1 M
) and recording (approximately 2 M) glass capillary microelectrodes (Harvard Apparatus) filled with ACSF. The stimulating electrode was placed in the Schaffer collateral/commissural pathway of the CA1, and recordings were made from the CA1 s. radiatum. Stimulus frequency was 0.033 Hz, duration was 0.1 ms, and intensity was 2–8 V. The stimulation intensity was set at approximately 40% of maximal EPSP amplitude as determined from an input-output curve for each experiment. Stable baseline recordings were made for 20 min prior to application of drug/LTP induction. EPSPs obtained were amplified x100 using a Brownlee Precision (model 410) instrumentation amplifier, displayed on an Iso-tech ISP622 oscilloscope, and recorded and analyzed using software supplied by Dr. J. Dempster (Strathclyde University). LTP was induced by three bursts of high-frequency stimulation (10 trains of 10 pulses at 200 Hz) given at 20-s intervals, with no change in stimulation intensity. Drugs were applied via the perfusion media. Verapamil (20 µM) and diltiazem (50 µM) were added 20 min pre-HFS. A25–35 (500 nM) was added to the perfusate 1 h pretetanus. Co-application of both A25–35 and verapamil/diltiazem took place 1 h pretetanus. Drugs were maintained within the perfusate for the duration of each experiment.
Data analysis
The EPSP slope was used to measure synaptic efficacy. EPSPs are expressed as a percentage of the mean initial slope measured during the last 10 min of the baseline-recording period prior to LTP induction. LTP data were analyzed using a two-way ANOVA, which examined all data recorded between 55 and 60 min post-HFS. The significance level was set at P < 0.05. Error bars on the graphs shown represent SE. Data insets are an average of four consecutive EPSPs recorded at the time indicated on the graph. Control experiments in vitro and in vivo were performed between test experiments.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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25–35 caused a depression of LTP
Administration of A25–35 or vehicle (distilled water) had no significant effect on baseline synaptic transmission, in vivo or in vitro (Fig. 1, A and B). In the hippocampal slice preparation, prior administration of 500 nM A25–35 caused a significant impairment of LTP (139 ± 5%, n = 12, P < 0.001, F = 110.5) with respect to vehicle controls (169 ± 7%, n = 9, Fig. 1A).
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Injection of 10 nmol A25–35 (icv) 1 h prior to HFS, however, caused a significant depression of LTP in vivo (128 ± 10%, n = 6, P < 0.001, F = 97.98) compared with control values (176 ± 10%, n = 6, Fig. 1B).
Verapamil impairs LTP
IN VITRO. In the slice preparation, administration of verapamil (20 µM) had no significant effect on baseline responses; however, following HFS in the presence of verapamil, LTP was depressed significantly (132 ± 4%, n = 6, P < 0.001, F = 125) compared with the control value (169 ± 7%; Fig. 2A).
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IN VIVO. In control experiments, injection of distilled water vehicle (0.5 µl ip) had no effect on baseline synaptic transmission, and following a high-frequency stimulus, robust LTP was produced in the control group (178 ± 11%, n = 7). Injection of either 1 or 10 mg/kg verapamil (ip) also had no significant effect on baseline recordings when measured up to 1 h postinjection. Both concentrations, however, significantly depressed LTP when measured 1 h post-HFS compared with control (139 ± 5%, n = 5, P < 0.001, F = 62.06; and 127 ± 10, n = 6, P < 0.001, F = 96.10; respectively; Fig. 2B).
Diltiazem reduces LTP
IN VITRO. In the slice preparation, diltiazem (50 µM) had no effect on baseline synaptic transmission when administered 20 min prior to HFS; however, diltiazem caused a significant impairment of LTP (123 ± 4%, n = 7, P < 0.001, F = 236.3) compared with vehicle controls (169 ± 7%; Fig. 3A).
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IN VIVO. Following injection (ip) of a second class of L-type calcium channel antagonist, diltiazem, at 1 or 10 mg/kg, there was no significant effect on baseline EPSPs. LTP was depressed significantly, however (1 mg: 146 ± 10, n = 6, P < 0.001, F = 34.72; and 10 mg: 130 ± 10%, n = 6, P < 0.001, F = 57.38) compared with control values (178 ± 11%, n = 7; Fig. 3B).
Verapamil attenuates the A25–35-induced depression of LTP
IN VIVO. A25–35 (10 nmol, icv) and verapamil (ip) at concentrations of 1 or 10 mg/kg were co-injected 1 h prior to LTP induction. Co-application of A25–35 and verapamil did not alter baseline synaptic transmission (Fig. 4, A and B). Injection of A25–35 with verapamil (1 mg/kg) produced a similar LTP (176 ± 7%, n = 6, P = 0.947, F = 0.0052) to that seen for controls (178 ± 11%; Fig. 4A). The level of LTP produced in this group was significantly different to that observed following application of verapamil (1 mg/kg; 139 ± 5%) or A25–35 (128 ± 10%) alone. Co-administration of A25–35 and a higher concentration of verapamil (10 mg/kg) also produced a smaller, yet significant, reversal of the A25–35-induced depression of LTP (169 ± 11%, n = 5, P = 0.06, F = 4.33; Fig. 4B).
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IN VITRO. Using the slice preparation, verapamil (20 µM) and A25–35 (500 nM) were superfused for 1 h prior to the induction of LTP. In the presence of both agents, the level of LTP produced (159 ± 7%, n = 6) was similar to that recorded under control conditions (169 ± 7%, P = 0.0993, F = 2.759), yet significantly different to that produced following application of A25–35 (139 ± 5%, n = 12, P < 0.001, F = 58.8) or verapamil (132 ± 4%, P < 0.001, F = 107) alone (Fig. 5)
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Diltiazem failed to reverse the A25–35 -induced impairment of LTP
IN VIVO. Diltiazem, at concentrations of 1 or 10 mg/kg, was co-applied with A25–35 (10 nmol) 1 h pretetanus. However, unlike verapamil, co-administration of A25–35 and 1 mg/kg diltiazem produced an LTP (149 ± 11%, n = 6) that was significantly different to that seen in controls (178 ± 11%, P < 0.001, F = 25.11; Fig. 6A). Similarly, co-application of the higher dose of diltiazem (10 mg/kg) failed to reverse the A25–35-induced depression of LTP (135 ± 5%, n = 6, P < 0.001, F = 94.57; Fig. 6B).
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IN VITRO. In the slice preparation, we also found that co-administration of A25–35 and diltiazem produced a significant depression of LTP (98 ± 7%, n = 5, P < 0.001, F = 404) compared with control values (169 ± 7%). The degree of potentiation produced was, however, significantly lower than that seen following application of diltiazem (123 ± 4%, P < 0.001, F = 108.8) or A25–35 (139 ± 5%, P < 0.001, F = 189.5) alone (Fig. 7).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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25–35 (Freir et al. 2001) and A1–40 (Cullen et al. 1997) significantly impaired LTP. Similar studies in vitro have also shown that treatment of hippocampal slices with A25–35 (Chen et al. 2000; Saleshando and O'Connor 2000) can cause an inhibition of LTP. More recently, soluble oligomers of A25–35 have been reported to impair LTP in the hippocampus both in vitro (Wang et al. 2002) and in vivo (Walsh et al. 2002).
LTP is regarded by many as a cellular correlate for certain forms of learning and memory (Bliss and Collingridge 1993; Malenka 1994). A depression of LTP, with corresponding deficits in memory-based performance tasks, has also been documented in vivo in transgenic mice carrying the Swedish mutation of AD (Chapman et al. 1999). In our study, we report a significant depression of LTP in area CA1 in vivo and in vitro following administration of the 11 amino acid peptide A25–35. An understanding of the mechanisms by which A leads to impairment of LTP and perhaps memory formation is therefore critical to explain a role for A in the pathology of AD.
A has been reported to disrupt calcium homeostasis in cultured cells, which can lead to apoptosis in cultured cortical neurons (Huang et al. 2000). An intracellular rise in postsynaptic calcium has been shown to be a critical and necessary event in the induction of LTP (Lynch et al. 1983; Malenka et al. 1988). Disruption of calcium dynamics by A peptide may explain the depression of LTP observed in this and previous studies. Evidence for a link between A25–35 and altered intracellular calcium levels is suggested by reports showing a direct interaction of A25–35 and calcium channels present on cell membranes. A peptide can cause a potentiation of Ca2+ influx through L-type (Ueda et al. 1997) and both L- and N-type VDCCs (MacManus et al. 2000) in cultured neurons. A rise in intracellular calcium concentration mediated by activation of L-type VDCCs in microglial cells following A25–35 administration has also been reported (Silei et al. 1999). A fragments have also been shown to induce calcium influx through L-type channels via activation of mitogen-activated protein kinase (MAPK) (Ekinci et al. 1999). In addition, postmortem analysis of hippocampi from AD patients revealed a significant increase in the number of L-type VDDCs in area CA1 and the dentate gyrus compared with age-matched controls (Coon et al. 1999). In our study, we investigated whether reducing the activity of L-type VDCCs with two separate channel blockers, verapamil and diltiazem, could attenuate the A25–35-induced impairment of LTP induced by a 200-Hz stimulus that we have reported here and previously (Freir et al. 2001).
Verapamil, a phenylalkylamine, and diltiazem, a benzothiazepine, have been shown to block L-type voltage-gated calcium channels by binding to separate domains of the 
1 pore-forming subunit of these channels (for review, see Striessnig et al. 1998). Studies performed in vitro (Grover and Teyler 1990) and in vivo (Freir and Herron 2003; Morgan and Teyler 1999), using similar stimulation protocols as this present study, revealed a depression of LTP in area CA1 following prior application of L-type VDCC blockers. A similar role for L-type VDCCs in LTP in area CA3 (Kapur et al. 1998) and in the amygdala (Weisskopf et al. 1999) has also been documented. We found that administration of either diltiazem or verapamil produced a significant impairment of LTP in vitro and in vivo. This suggests that L-type VDCCs play a role in tetanically induced LTP in vitro and in vivo when using this high-frequency (200 Hz) protocol (Freir and Herron 2003; Grover and Teyler 1999; Morgan and Teyler 1990).
Since LTP was depressed following administration of A25–35 or L-type VDCC blockers, the effects of co-applying A25–35 and either diltiazem or verapamil were investigated. Co-application of A25–35 and either 1 or 10 mg/kg verapamil in vivo produced an LTP that was similar to that seen in control animals. Similarly, in the slice preparation, perfusion of both agents reversed not only the A25–35 but also the verapamil-induced depression of LTP observed previously. Surprisingly, however, we did not see a reversal in the depression of LTP caused by either A or diltiazem following co-application of both compounds. This suggests that there may be a differential mode of action of these channel blockers with respect to A25–35. One possibility is a potential interaction between A25–35 and verapamil, which reduces the effect of each drug alone on LTP. Diltiazem, a structurally different compound, may not interact with A25–35 in a similar manner, allowing each compound to produce a significant depression of LTP alone. Our in vitro study suggests that co-application of A25–35 and diltiazem produces a depression of LTP significantly greater than that seen in the presence of either agent alone, although this was not observed in vivo. A second possibility is that, despite evidence of an interaction between A25–35 and L-type VDCCs (Eknici et al. 1999; Ueda et al. 1997), the A25–35-mediated depression of LTP may be due to an interaction with other channels/signaling mechanisms. If this is the case, some non-specific action of verapamil such as block of potassium channels (Rauer and Grismer 1996) may explain the differences in action of verapmil and diltiazem. Reports suggest that verapamil may also block N-type VDCCs (Kelley et al. 1996). A recent study in cultured cortical neurons suggested that A mediates calcium influx through both L- and N-type VDCCs (MacManus et al. 2000). Verapamil may therefore reverse the A-induced depression of LTP via an action on N-type channels. Finally, A has been reported to form nonspecific cation channels in lipid membranes (Arispe et al. 1994) and in cultured neurons (Bhatia et al. 2000). It is possible therefore that verapamil may be more effective than diltiazem at reducing calcium influx through these A-formed channels. Aside from its effects on L-type calcium channels, verapmail can also act as an antagonist of p-glycoprotein transporters (p-gps) or multidrug resistance proteins (MDRPs) (Pajeva and Wiese 2002). There is now evidence that p-gps act as A efflux pumps (Lam et al. 2001). Deposition of -amyloid has been shown to be inversely correlated with p-gp expression in the brains of elderly nondemented humans (Vogelgesang et al. 2002). p-gp transporters are known to be present in the endothelial cells that form the blood brain barrier (Jonker et al. 1999). Recently, mRNAs encoding p-gps have been demonstrated in cultured neurons and glial (Hirrlinger et al. 2002), suggesting that these transporters may play a significant role in membrane trafficking within the brain. It is possible therefore that verapamil may alter A-mediated effects in the hippocampus via an interaction with p-gps.
There appears to be a balance between the concentration of verapamil used in vivo and the reversal of the A-induced depression of LTP. Injection of 1 mg/kg verapamil, which caused a smaller depression of LTP when injected alone, reversed fully the A effect on LTP. A higher concentration of 10 mg/kg verapamil also reversed the A-mediated impairment of LTP but to a lesser extent. It is possible therefore that there is a fine balance between a potential activation of L-type VDCCs by A and a block of these L-type calcium channels by verapamil leading to the production of LTP similar to that in controls. However, this hypothesis requires further examination.
To conclude, we have demonstrated a significant depression of LTP when L-type VDCC blockers were applied either in vitro or in vivo, in agreement with previous studies, suggesting a role for L-type calcium channels in LTP in area CA1 (Freir and Herron 2003; Grover and Teyler 1990; Morgan and Teyler 1999). We have also shown an impairment of LTP following administration of A25–35 both in vivo and in vitro. Co-application of verapamil and A was found to reverse both the A and the verapamil-induced depression of LTP. Co-application of diltiazem with A, however, did not result in a reversal of the effects of either agent alone. Although L-type calcium channel antagonists, including verapamil, are used in the treatment of cardiovascular disorders such as angina, hypertension, and cardiac arrhythmias, these results suggest that verapamil or similar compounds may be useful in the treatment of AD.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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FOOTNOTES |
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Address for reprint requests: C. E.Herron, Dept. of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, Univ. College Dublin, Earlsfort Terrace, Dublin 2, Ireland (E-mail: Caroline.Herron{at}ucd.ie).
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REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
Bhatia R, Lin H, and Lal R. Fresh and globular amyloid beta protein (1–42) induces rapid cellular degeneration: evidence for AP channel-mediated cellular toxicity. FASEB J 9: 1233–1243, 2000.
Bliss TV and Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361: 31–39, 1993.[Medline]
Chapman PF, White GL, Jones MW, Cooper-Blacketer D, Marshall VJ, Irizarry M, Younkin L, Good MA, Bliss TV, Hyman BT, Younkin SG, and Hsiao KK. Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci 3: 271–276, 1999.
Chen QS, Kagan BL, Hirakura Y, and Xie CW. Impairment of hippocampal long-term potentiation by Alzheimer amyloid beta-peptides. J Neurosci Res 60: 65–72, 2000.[ISI][Medline]
Coon AL, Wallace DR, Mactutus CF, and Booze RM. L-type calcium channels in the hippocampus and cerebellum of Alzheimer's disease brain tissue. Neurobiol Aging 20: 597–603, 1999.[ISI][Medline]
Costello D and Herron CE. Interaction of L-type calcium channel blockers and A [25-35] on long term potentiation in the hippocampal CA1 in vitro. Eur J Physiology 443S: P28–7, 2002.
Cullen WK, Suh YH, Anwyl R, and Rowan MJ. Block of LTP in rat hippocampus in vivo by beta-amyloid precursor protein fragments. Neuroreport 8: 3213–3217, 1997.[ISI][Medline]
Ekinci FJ, Malik KU, and Shea TB. Activation of the L voltage-sensitive calcium channel by mitogen-activated protein (MAP) kinase following exposure of neuronal cells to beta-amyloid. MAP kinase mediates beta-amyloid-induced neurodegeneration. J Biol Chem 274: 30322–30327, 1999.
Freir DB, Holscher C, and Herron CE. Blockade of long-term potentiation by beta-amyloid peptides in the CA1 region of the rat hippocampus in vivo. J Neurophysiol 85: 708–713, 2001.
Freir DB and Herron CE. The L-type Ca2+ channel blockers verapamil and diltiazem attenuate A-induced impairment of LTP in area CA1 of the anaesthetised rat. J Physiol 531P: 107P, 2001.
Freir DB and Herron CE. Nicotine enhances the depressive actions of A1-40 on long-term potentiation in the rat hippocampal CA1 region in vivo. J Neurophysiol 89: 2917–2922, 2003.
Green KN and Peers C. Amyloid beta peptides mediate hypoxic augmentation of Ca2+ channels. J Neurochem 77: 953–956, 2001.[ISI][Medline]
Grover LM and Teyler TJ. Two components of long-term potentiation induced by different patterns of afferent activation. Nature 347: 477–479, 1990.[Medline]
Hirrlinger J, Konig J, and Dringen R. Expression of mRNAs of multidrug resistence proteins (Mrps) in cultured rat astrocytes, oligodendrocytes, microglial cells and neurones. J Neurochem 82: 716–719, 2002.[ISI][Medline]
Holdright D. Calcium-channel antagonists in cardiovascular disease, Br J Hosp Med 57: 552–556, 1997.[ISI][Medline]
Huang HM, Ou HC, and Hsieh SJ. Antioxidants prevent amyloid peptide-induced apoptosis and alteration of calcium homeostasis in cultured cortical neurons. Life Sci 66: 1879–1892, 2000.[ISI][Medline]
Jonker JW, Wagenaar E, van Deemter L, Gottschlich R, Bender HM, Dasenbrock J, and Schinkel AH. Role of blood-brain barrier P-glycoprotein in limiting brain accumulation and sedative side-effects of asimadoline, a peripherally acting analgaesic drug. Br J Pharmacol 127: 43–50, 1999.[ISI][Medline]
Kapur A, Yeckel MF, Gray R, and Johnston D. L-type calcium channels are required for one form of hippocampal mossy fibre LTP. J Neurophysiol 79: 2181–2190, 1998.
Kelley SR, Kamal TJ, and Molitch ME. Mechanism of verapamil calcium channel blockade-induced hyperprolactinemia. Am J Physiol 270: E96–E100, 1996.[Medline]
Lam FC, Liu R, Lu P, Shapiro AB, Renoir J-M, Sharom FJ, and Reiner PB. -Amyloid efflux mediated by p-glycoprotein. J Neurochem 76: 1121–1128, 2001.[ISI][Medline]
Lippa CF, Nee LE, Mori H, and St. George-Hyslop P. A-42 deposition precedes other changes in PS-1 Alzheimer's disease. Lancet 352: 1117–1118, 1998.[ISI][Medline]
Lynch G, Larson J, Kelso S, Barrionuevo G, and Schottler F. Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature 305: 719–721, 1983.[Medline]
MacManus A, Ramsden M, Murray M, Henderson Z, Pearson HA, and Campbell VA. Enhancement of Ca2+ influx and voltage-dependent Ca2+ channel activity by beta-amyloid-(1–40) in rat cortical synaptosomes and cultured cortical neurons. Modulation by the proinflammatory cytokine interleukin-1. J Biol Chem 275: 4713–4718, 2000.
Malenka RC. Synaptic plasticity in the hippocampus: LTP and LTD. Cell 78: 535–538, 1994.[ISI][Medline]
Malenka RC, Kauer JA, Zucker RS, and Nicoll RA. Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission. Science 242: 81–84, 1988.
Mattson MP, Partin J and Begley JG. Amyloid beta-peptide induces apoptosis-related events in synapses and dendrites. Brain Res, 807: 167–76, 1998.[ISI][Medline]
Michaluk J, Karolewicz B, Antkiewicz-Michaluk L, and Vetulani J. Effects of various Ca2+ channel antagonists on morphine analgesia, tolerance and dependence, and on blood pressure in the rat. Eur J Pharmacol 352: 189–197, 1998.[ISI][Medline]
Morgan SL and Teyler TJ. VDCCs and NMDARs underlie two forms of LTP in CA1 hippocampus in vivo. J Neurophysiol 82: 736–740, 1999.
Morris RG, Garrud P, Rawlins JN, and O'Keefe J. Place navigation impaired in rats with hippocampal lesions. Nature 297: 681–683, 1982.[Medline]
Pajeva IK and Wiese M. Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis). J Med Chem 45: 5671–5686, 2002.[ISI][Medline]
Saleshando G and O'Connor JJ. SB203580, the p38 mitogen-activated protein kinase inhibitor blocks the inhibitory effect of beta-amyloid on long-term potentiation in the rat hippocampus. Neurosci Lett 288: 119–122, 2000.[ISI][Medline]
Selkoe DJ. Alzheimer's disease: genotypes, phenotypes, and treatments. Science 275: 630–631, 1997.
Silei V, Fabrizi C, Venturini G, Salmona M, Bugiani O, Tagliavini F, and Lauro GM. Activation of microglial cells by PrP and beta-amyloid fragments raises intracellular calcium through L-type voltage sensitive calcium channels. Brain Res 818: 168–170, 1999.[ISI][Medline]
Stephan A, Laroche S, and Davis S. Generation of aggregated beta-amyloid in the rat hippocampus impairs synaptic transmission and plasticity and causes memory deficits. J Neurosci 21: 5703–5714, 2001.
Striessnig J, Grabner M, Mitterdorfer J, Hering S, Sinnegger MJ, and Glossmann H. Structural basis of drug binding to L Ca2+ channels, Trends Pharmacol Sci 19: 108–115, 1998.[Medline]
Ueda K, Shinohara S, Yagami T, Asakura K, and Kawasaki K. Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals. J Neurochem 68: 265–271, 1997.[ISI][Medline]
Vogelgesang S, Cascorbi I, Schroder E, Pahnke J, Kroemer H, Siegmund W, Kunert-Keil C, Walker LC, and Warzok R. Deposition of Alzheimer's beta-amyloid is inversely correlated with p-glycoprotein expression in the brains of elderly non-demented humans. Pharmacogenetics 12: 535–541, 2002.[ISI][Medline]
Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, and Selkoe DJ. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416: 535–539, 2002.[Medline]
Wang HW, Pasternak JF, Kuo H, Ristic H, Lambert MP, Chromy B, Viola KL, Klein WL, Stine WB, Krafft GA, and Trommer BL. Soluble oligomers of beta amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus. Brain Res 924: 133–140, 2002.[ISI][Medline]
Weisskopf MG, Bauer EP, and Le Doux JE. L-type voltage-gated calcium channels mediate NMDA-independent associative long-term potentiation at thalamic input synapses to the amygdala. J. Neurosci 19: 10512–10519, 1999.
Yan XZ, Qiao JT, Dou Y, and Qiao ZD. Beta-amyloid peptide fragment 31–35 induces apoptosis in cultured cortical neurons. Neuroscience 92: 177–184, 1999.[ISI][Medline]
Yankner BA, Duffy LK, and Kirschner DA. Neurotrophic and neurotoxic effects of amyloid protein: reversal by tachykinin neuropeptides. Science 250: 279–282, 1990.
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) 1 h prior to high frequency stimulation (HFS) caused a significant impairment of LTP (139 ± 5%, n = 12) in vitro compared with controls (
, 169 ± 7%, n = 9, P < 0.05). B: injection of 10 nmol A
; 139 ± 5%, n = 5) and the 10 mg/kg (
) group (127 ± 10%, n = 6) was impaired with respect to control values (
