Nicotine Enhances the Depressive Actions of Aβ1–40 on Long-Term Potentiation in the Rat Hippocampal CA1 Region In Vivo

2003 ◽  
Vol 89 (6) ◽  
pp. 2917-2922 ◽  
Author(s):  
D. B. Freir ◽  
C. E. Herron
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
High Affinity ◽  
Ca1 Region ◽  
Α7 Nachr ◽  
Term Potentiation ◽  
Significant Depression

Hippocampal long-term potentiation (LTP) is a form of synaptic plasticity used as a cellular model of memory. Beta amyloid (Aβ) is involved in Alzheimer's disease (AD), a neurode-generative disorder leading to cognitive deficits. Nicotine is also claimed to act as a cognitive enhancer. Aβ is known to bind with high affinity to the α7-nicotinic acetylcholine receptor (nAChR). Here we have investigated the effect of intracerebroventricular (icv) injection of the endogenous peptide Aβ1–40 on LTP in area CA1 of urethananesthetized rats. We also examined the effect of Aβ12–28 (icv), which binds with high affinity to the α7-nAChR and the specific α7-nAChR antagonist methyllycaconitine (MLA) on LTP. We found that Aβ12–28 had no effect on LTP, whereas MLA depressed significantly LTP, suggesting that activation of the α7-nAChR is a requirement for LTP. Within the in vivo environment, where other factors may compete with Aβ12–28 for binding to α7-nAChR, it does not appear to modulate LTP. To determine if the depressive action of Aβ1–40 on LTP could be modulated by nicotine, these agents were also co-applied. Injection of 1 or 10 nmol Aβ1–40 caused a significant depression of LTP, whereas nicotine alone (3 mg/kg) had no effect on LTP. Co-injection of nicotine with Aβ1–40 1 h prior to LTP induction caused a further significant depression of LTP compared with Aβ1–40 alone. These results demonstrate that nicotine enhances the deficit in LTP produced by Aβ1–40. This then suggests that nicotine may exacerbate the depressive actions of Aβ on synaptic plasticity in AD.

Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Yu-Xing Ge ◽  
Ying-Ying Lin ◽  
Qian-Qian Bi ◽  
Yu-Juan Chen
Keyword(s):  
Synaptic Plasticity ◽  
Temporal Lobe Epilepsy ◽  
Synaptic Vesicle ◽  
Long Term Potentiation ◽  
Synaptic Dysfunction ◽  
Over Expression ◽  
Term Potentiation ◽  
Synaptic Vesicle Protein 2A

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

scholarly journals Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Enrico Faldini ◽  
Tariq Ahmed ◽  
Luc Bueé ◽  
David Blum ◽  
Detlef Balschun
Keyword(s):  
Synaptic Plasticity ◽  
Transgenic Mice ◽  
Mouse Models ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Synaptic Loss ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Frequency Stimulation

AbstractMany mouse models of Alzheimer’s disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V mutations and show normal LTP upon high-frequency-stimulation (HFS), develop severe changes in NMDAR mediated long-term-depression (LTD), the physiological counterpart of LTP. In the present study, we focused on putative effects of AD-related pathologies on depotentiation (DP), another form of synaptic plasticity. Using a novel protocol to induce DP in the CA1-region, we found in 11–15 months old male THY-Tau22 and APPPS1–21 transgenic mice that DP was not deteriorated by Aß pathology while significantly compromised by Tau pathology. Our findings advocate DP as a complementary form of synaptic plasticity that may help in elucidating synaptic pathomechanisms associated with different types of dementia.

scholarly journals Widespread promoter methylation of synaptic plasticity genes in long-term potentiation in the adult brain in vivo

BMC Genomics ◽  
2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Jesper L. V. Maag ◽  
Dominik C. Kaczorowski ◽  
Debabrata Panja ◽  
Timothy J. Peters ◽  
Clive R. Bramham ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Promoter Methylation ◽  
Long Term Potentiation ◽  
Adult Brain ◽  
Term Potentiation

scholarly journals Specific Roles of AMPA Receptor Subunit GluR1 (GluA1) Phosphorylation Sites in Regulating Synaptic Plasticity in the CA1 Region of Hippocampus

2010 ◽  
Vol 103 (1) ◽  
pp. 479-489 ◽  
Author(s):  
Hey-Kyoung Lee ◽  
Kogo Takamiya ◽  
Kaiwen He ◽  
Lihua Song ◽  
Richard L. Huganir
Keyword(s):  
Synaptic Plasticity ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Phosphorylation Sites ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Ampa Receptor Subunit ◽  
Glur1 Subunit ◽  
Activity Dependent

Activity-dependent changes in excitatory synaptic transmission in the CNS have been shown to depend on the regulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). In particular, several lines of evidence suggest that reversible phosphorylation of AMPAR subunit glutamate receptor 1 (GluR1, also referred to as GluA1 or GluR-A) plays a role in long-term potentiation (LTP) and long-term depression (LTD). We previously reported that regulation of serines (S) 831 and 845 on the GluR1 subunit may play a critical role in bidirectional synaptic plasticity in the Schaffer collateral inputs to CA1. Specifically, gene knockin mice lacking both S831 and S845 phosphorylation sites (“double phosphomutants”), where both serine residues were replaced by alanines (A), showed a faster decaying LTP and a deficit in LTD. To determine which of the two phosphorylation sites was responsible for the phenotype, we have now generated two lines of gene knockin mice: one that specifically lacks S831 (S831A mutants) and another that lacks only S845 (S845A mutants). We found that S831A mutants display normal LTP and LTD, whereas S845A mutants show a specific deficit in LTD. Taken together with our previous results from the “double phosphomutants,” our data suggest that either S831 or S845 alone may support LTP, whereas the S845 site is critical for LTD expression.

scholarly journals Simvastatin Impairs Hippocampal Synaptic Plasticity and Cognitive Function in Mice

2021 ◽  
Author(s):  
Yujun Guo ◽  
Guichang Zou ◽  
Keke Qi ◽  
Jin Jin ◽  
Lei Yao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Drug Discontinuation ◽  
Cholesterol Levels ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation ◽  
The Central Nervous System

Abstract Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive

scholarly journals Effects of perfluorooctane sulfonate and its alternatives on long-term potentiation in the hippocampus CA1 region of adult rats in vivo

2016 ◽  
Vol 5 (2) ◽  
pp. 539-546 ◽  
Author(s):  
Qian Zhang ◽  
Wei Liu ◽  
Qiao Niu ◽  
Yu Wang ◽  
Huimin Zhao ◽  
...  
Keyword(s):  
Health Effects ◽  
Perfluorooctane Sulfonate ◽  
Long Term Potentiation ◽  
Adult Rats ◽  
Ca1 Region ◽  
Term Potentiation

With the limited but ongoing usage of perfluorooctane sulfonate (PFOS), the health effects of both PFOS and its alternatives are far from being understood.

scholarly journals Effects of the hydroalcoholic extract of Rosa damascena on hippocampal long-term potentiation in rats fed high-fat diet

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Seyed Asaad Karimi ◽  
Somayeh Komaki ◽  
Masoumeh Taheri ◽  
Ghazaleh Omidi ◽  
Masoumeh Kourosh-Arami ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Rosa Damascena ◽  
High Fat ◽  
Oxidative Stress Biomarkers ◽  
Hydroalcoholic Extract ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation

AbstractHigh-fat diets (HFDs) and obesity can cause serious health problems, such as neurodegenerative diseases and cognitive impairments. Consumption of HFD is associated with reduction in hippocampal synaptic plasticity. Rosa damascena (R. damascena) is traditionally used as a dietary supplement for many disorders. This study was carried out to determine the beneficial effect of hydroalcoholic extract of R. damascena on in vivo hippocampal synaptic plasticity (long-term potentiation, LTP) in the perforant pathway (PP)—dentate gyrus (DG) pathway in rats fed with an HFD. Male Wistar rats were randomly assigned to four groups: Control, R. damascena extract (1 g/kg bw daily for 30 days), HFD (for 90 days) and HFD + extract. The population spike (PS) amplitude and slope of excitatory post-synaptic potentials (EPSP) were measured in DG area in response to stimulation applied to the PP. Serum oxidative stress biomarkers [total thiol group (TTG) and superoxide dismutase (SOD)] were measured. The results showed the HFD impaired LTP induction in the PP-DG synapses. This conclusion is supported by decreased EPSP slope and PS amplitude of LTP. R. damascena supplementation in HFD animals enhanced EPSP slope and PS amplitude of LTP in the granular cell of DG. Consumption of HFD decreased TTG and SOD. R. damascena extract consumption in the HFD animals enhanced TTG and SOD. These data indicate that R. damascena dietary supplementation can ameliorate HFD-induced alteration of synaptic plasticity, probably through its significant antioxidant effects and activate signalling pathways, which are critical in controlling synaptic plasticity.

Aβ25–35-Induced Depression of Long-Term Potentiation in Area CA1 In Vivo and In Vitro Is Attenuated by Verapamil

2003 ◽  
Vol 89 (6) ◽  
pp. 3061-3069 ◽  
Author(s):  
D. B. Freir ◽  
D. A. Costello ◽  
C. E. Herron
Keyword(s):  
Long Term Potentiation ◽  
Slice Preparation ◽  
Ca1 Region ◽  
Combined Application ◽  
Significant Reversal ◽  
Term Potentiation ◽  
Prior Application

The effect of intracerebroventricular (icv) injection of Aβ25–35 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 Aβ25–35 (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 Aβ25–35 (500 nmol), verapamil (20 μM), or diltiazem (50 μM). Combined application of Aβ25–35 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 Aβ25–35 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 Aβ 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.

Blockade of Long-Term Potentiation by β-Amyloid Peptides in the CA1 Region of the Rat Hippocampus In Vivo

2001 ◽  
Vol 85 (2) ◽  
pp. 708-713 ◽  
Author(s):  
Darragh B. Freir ◽  
Christian Holscher ◽  
Caroline E. Herron
Keyword(s):  
Long Term Potentiation ◽  
Amyloid Peptide ◽  
Excitatory Postsynaptic Potential ◽  
Dependent Manner ◽  
Aβ Peptides ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Β Amyloid

The effect of intracerebroventricular (icv) injections of β-amyloid peptide fragments Aβ[15–25], Aβ[25–35], and Aβ[35–25] were examined on synaptic transmission and long-term potentiation (LTP) in the hippocampal CA1 region in vivo. Rats were anesthetized using urethan, and changes in synaptic efficacy were determined from the slope of the excitatory postsynaptic potential (EPSP). Baseline synaptic responses were monitored for 30 min prior to icv injection of Aβ peptides or vehicle. High-frequency stimulation (HFS) to induce LTP was applied to the Schaffer-collateral pathway 5 min or 1 h following the icv injection. HFS comprised 3 episodes of 10 stimuli at 200 Hz, 10 times, applied at 30-s intervals. Normal LTP measured 30 min following HFS, was produced following icv injection of vehicle (191 ± 17%, mean ± SE, n = 6) or Aβ[15–25; 100 nmol] (177 ± 6%, n = 6) 1 h prior to HFS. LTP was, however, markedly reduced by Aβ[25–35; 10 nmol] (129 ± 9%, n = 6, P < 0.001) and blocked by Aβ[25–35; 100 nmol] (99 ± 6%, n = 6, P < 0.001). Injection of the reverse peptide, Aβ[35–25], also impaired LTP at concentrations of 10 nmol (136 ± 3%, n = 6, P < 0.01) and 100 nmol (144 ± 7, n = 8, P < 0.05). Using a different protocol, HFS was delivered 5 min following Aβ injections, and LTP was measured 1 h post HFS. Stable LTP was produced in the control group (188 ± 15%, n = 7) and blocked by Aβ[25–35, 100 nmol] (108 ± 15%, n = 6, P < 0.001). A lower dose of Aβ[25–35; 10 nmol] did not significantly impair LTP (176 ± 30%, n = 4). The Aβ-peptides tested were also shown to have no significant effect on paired pulse facilitation (interstimulus interval of 50 ms), suggesting that neither presynaptic transmitter release or activity of interneurons in vivo are affected. The effects of Aβ on LTP are therefore likely to be mediated via a postsynaptic mechanism. This in vivo model of LTP is extremely sensitive to Aβ-peptides that can impair LTP in a time- ([25–35]) and concentration-dependent manner ([25–35] and [35–25]). These effects of Aβ-peptides may then contribute to the cognitive deficits associated with Alzheimer's disease.

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