Long-term Potentiation In Rat Hippocampus Research Articles

Enriched environment rescues neonatal pain induced cognitive deficits and the impaired hippocampal synaptic plasticity later in life.

Although extensive and untreated pain that occurs during a critical developmental window may impair cognition later in life, environmental interventions early in life might promote cognition. However, the underlying mechanism is poorly understood. Our current study utilized a rat model of "repetitive needle pricks" from the day of birth (P0) to postnatal day 7 (P7) to mimic the painful experience of preterm neonates in the neonatal intensive care unit. Enriched environment (EE) during development period (from P15 to P70) was implemented as a nonpharmacological intervention approach. Electrophysiological recording, behavioral tests, and biochemical analysis were performed after the end of EE (between P71 and P80). The results showed neonatal repetitive pain resulted in a reduction in mechanical withdrawal thresholds by the von Frey test in P70 (p<.001). Furthermore, neonatal repetitive pain impaired spatial learning and memory (p<.05) and even led to dysfunction in fear memory (p<.01). In contrast, EE rescued neonatal pain-induced cognitive deficits and normalized hippocampal long-term potentiation in rats exposed to neonatal pain (p <<.05). The beneficial effect of EE might be the improvements in hippocampal synaptic plasticity via upregulating neurotrophic factors and N-methyl-d-aspartate (NMDA) receptors in the hippocampus. Our findings provide evidence that early environmental intervention might be a safe strategy to overcome neurodevelopmental abnormalities in preterm infants who experienced multiple procedural painful events during the early critical period.

Losartan improved hippocampal long-term potentiation impairment induced by repeated LPS injection in rats.

Cognitive impairment has been known as a common consequence of brain inflammation. Long‐term potentiation (LTP), the generally accepted cellular mechanism for memory formation in the mammalian brain, has been shown to be suppressed by inflammation. Studies have shown that angiotensin II (Ang II) through the Ang II type 1 receptor (AT1R) has a role in brain and peripheral immune system communication and brain inflammation. Here, the effect of AT1R blockade on hippocampal LTP in rats undergoing repeated lipopolysaccharide (LPS) injection was investigated. Rats received intraperitoneal (ip) injections of LPS (250 μg kg−1 day−1) for seven days. Treatment with losartan (ip; 3 mg kg−1 day−1) was started 3 days before LPS injection and continued during the LPS injections. Rats were anesthetized, and field excitatory postsynaptic potential (fEPSP) was recorded from the stratum radiatum of the CA1 area of the hippocampus in response to stimulation of the Schaffer collateral pathway. Results showed that LTP was suppressed in the LPS‐injected rats as no significant differences were found in the fEPSP slope and amplitude before and after the LTP induction. AT1R blockade by losartan restored fEPSP to the control levels. These findings indicate that Ang II, through AT1R, has a role in LTP suppression induced by systemic inflammation.

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

High-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.

Shortened tethering filaments stabilize presynaptic vesicles in support of elevated release probability during LTP in rat hippocampus

Long-term potentiation (LTP) is a cellular mechanism of learning and memory that results in a sustained increase in the probability of vesicular release of neurotransmitter. However, previous work in hippocampal area CA1 of the adult rat revealed that the total number of vesicles per synapse decreases following LTP, seemingly inconsistent with the elevated release probability. Here, electron-microscopic tomography (EMT) was used to assess whether changes in vesicle density or structure of vesicle tethering filaments at the active zone might explain the enhanced release probability following LTP. The spatial relationship of vesicles to the active zone varies with functional status. Tightly docked vesicles contact the presynaptic membrane, have partially formed SNARE complexes, and are primed for release of neurotransmitter upon the next action potential. Loosely docked vesicles are located within 8 nm of the presynaptic membrane where SNARE complexes begin to form. Nondocked vesicles comprise recycling and reserve pools. Vesicles are tethered to the active zone via filaments composed of molecules engaged in docking and release processes. The density of tightly docked vesicles was increased 2 h following LTP compared to control stimulation, whereas the densities of loosely docked or nondocked vesicles congregating within 45 nm above the active zones were unchanged. The tethering filaments on all vesicles were shorter and their attachment sites shifted closer to the active zone. These findings suggest that tethering filaments stabilize more vesicles in the primed state. Such changes would facilitate the long-lasting increase in release probability following LTP.

Effect of garlic powder on hippocampal long-term potentiation in rats fed high fat diet: an in vivo study.

The objective of this study was to determine the relation between the chronic consumption of garlic powder in combination with high-fat diet (HFD) on long term potentiation (LTP) in the dentate gyrus (DG) of rat hippocampus. Male rats were divided to 4 groups, control with the standard diet, control with a standard diet plus garlic, high-fat diet (HFD) group and high-fat diet with garlic. Following 6months of controlled dietary in each experimental group, the rats were anesthetized with i.p. injection of ketamine and xylazin (100 and 2.5mg/kg, respectively), and placed into a stereotaxic apparatus for surgery, electrode implantation and field potential recording. The population spike (PS) amplitude and slope of excitatory post synaptic potentials (EPSP) were measured in the DG area of adult rats in response to stimulation applied to the perforant path (PP) (by 400Hz tetanization). The results showed that garlic increased EPSP slope and PS amplitude respect to HFD group. It was suggested that the garlic powder administration could attenuate the deteriorating effect of HFD on in vivo hippocampal LTP in the granular cells of the DG.

The interactive role of CB1 receptors and L-type calcium channels in hippocampal long-term potentiation in rats

Long-term potentiation (LTP) of synaptic responses is a widely researched model of synaptic plasticity that occurs during learning and memory. The cannabinoid system is an endogenous system that modulate this kind of synaptic plasticity. In addition, voltage dependent calcium channels is essential for induction of LTP at some synapses in the hippocampus. However, there is currently debate over the interaction between L-type calcium channels and cannabinoid system on the synaptic plasticity. In this study, we examined the effects of an acute administration of the cannabinoid antagonist AM251 following a chronic administration of the Ca2+ channel blocker verapamil on LTP induction in the hippocampal dentate gyrus(DG) of rats. Male Wistar rats were administered verapamil(10,25,50mg/kg) or saline intraperitoneally(IP) daily for 13days(n=10/group). After this treatment period, animals were anesthetized with an IP injection of urethane; the recording and stimulating electrodes were positioned in the DG and the perforant pathway. After obtaining a steady state baseline response, a single IP injection of saline or AM251(1 or 5mg/kg) was administered. LTP was induced by high-frequency stimulation(HFS). The population spike(PS) amplitude and the slope of excitatory postsynaptic potentials(EPSP) were compared between the experimental groups. The acute administration of the CB1 antagonist AM251 increased LTP induction. The EPSP slopes and PS amplitude in the verapamil and AM251 groups differed after HFS, such that AM251 increased LTP, whereas verapamil decreased LTP induction. These findings suggest that there are functional interactions between the L-type calcium channels and cannabinoid system in this model of synaptic plasticity in the hippocampus.

Co-injection of Aβ1-40 and ApoE4 impaired spatial memory and hippocampal long-term potentiation in rats

Apolipoprotein E4 (APOE4) allele located on chromosome 19 is a major genetic risk factor for developing Alzheimer’s disease (AD). However, the direct effects of ApoE4 on the cognitive function and long-term synaptic plasticity have not fully investigated. At the same time, although amyloid beta protein (Aβ)-ApoE complexes are principal components of AD-associated brain damage, there is still lack of in vivo study on the effects of co-existed Aβ1-40 and ApoE4. In the present study, we examined the effects of ApoE4 on the spatial memory and hippocampal long term potentiation (LTP) by using Morris water maze test and in vivo field potential recording, compared the neurotoxicity of Aβ1-40 and ApoE4, and investigated the effects of co-application of Aβ1-40 and ApoE4 on cognitive behavior and synaptic plasticity. The results showed that intracerebrovenrticular (i.c.v.) injection of Aβ1-40 or ApoE4 significantly and similarly impaired spatial learning and memory, and depressed the high-frequency stimulus (HFS) induced LTP. Importantly, compared to the effects of Aβ1-40 or ApoE4 alone, co-injection of Aβ1-40 and ApoE4 produced much heavier damages in cognitive behaviors and long term synaptic plasticity. These results demonstrated that ApoE4 not only exerted direct neurotoxicity but also enhanced the neurotoxicity of Aβ1-40 on spatial cognitive function and hippocampal LTP, which maybe partly elucidates the mechanism by which APOE4 allele exerted negative effects as a major genetic risk factor for developing AD.

Sirt1 Regulates p53 Stability and Expression of Its Target S100B during Long-Term Potentiation in Rat Hippocampus.

Induction of long-term potentiation in rat hippocampus was followed by short-term activation of transcription factor p53 and its subsequent degradation. We studied the effects of EX-527 (inhibitor of deacetylase Sirt1, a negative regulator of p53) and pifi thrin-β (inhibitor of p53-dependent transcription) on the levels of p53 protein and mRNA of its target gene S100B during long-term potentiation. Pifi thrin-β limited the increase in S100B mRNA content after tetanization, which confi rmed signifi cant contribution of p53 in the regulation of S100B during long-term potentiation. EX-527 completely prevented p53 degradation and increased S100B expression induced by tetanization. Thus, Str1 regulates stability of p53 and expression of its target gene S100B in rat hippocampus during long-term potentiation.

Acute pentobarbital treatment impairs spatial learning and memory and hippocampal long-term potentiation in rats

Reports of the effects of pentobarbital on learning and memory are contradictory. Some studies have not shown any interference with learning and memory, whereas others have shown that pentobarbital impairs memory and that these impairments can last for long periods. However, it is unclear whether acute local microinjections of pentobarbital affect learning and memory, and if so, the potential mechanisms are also unclear. Here, we reported that the intra-hippocampal infusion of pentobarbital (8.0mM, 1μl per side) significantly impaired hippocampus-dependent spatial learning and memory retrieval. Moreover, in vitro electrophysiological recordings revealed that these behavioral changes were accompanied by impaired hippocampal CA1 long-term potentiation (LTP) and suppressed neuronal excitability as reflected by a decrease in the number of action potentials (APs). These results suggest that acute pentobarbital application causes spatial learning and memory deficits that might be attributable to the suppression of synaptic plasticity and neuronal excitability.

Involvement of protein kinase ζ in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity.

The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ζ (PKMζ) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKMζ is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ζ-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKMζ (p-PKMζ) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.5–2 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKMζ might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity.

KCNQ/Kv7 channel activator flupirtine protects against acute stress-induced impairments of spatial memory retrieval and hippocampal LTP in rats

Spatial memory retrieval and hippocampal long-term potentiation (LTP) are impaired by stress. KCNQ/Kv7 channels are closely associated with memory and the KCNQ/Kv7 channel activator flupirtine represents neuroprotective effects. This study aims to test whether KCNQ/Kv7 channel activation prevents acute stress-induced impairments of spatial memory retrieval and hippocampal LTP. Rats were placed on an elevated platform in the middle of a bright room for 30min to evoke acute stress. The expression of KCNQ/Kv7 subunits was analyzed at 1, 3 and 12h after stress by Western blotting. Spatial memory was examined by the Morris water maze (MWM) and the field excitatory postsynaptic potential (fEPSP) in the hippocampal CA1 area was recorded in vivo. Acute stress transiently decreased the expression of KCNQ2 and KCNQ3 in the hippocampus. Acute stress impaired the spatial memory retrieval and hippocampal LTP, the KCNQ/Kv7 channel activator flupirtine prevented the impairments, and the protective effects of flupirtine were blocked by XE-991 (10,10-bis(4-Pyridinylmethyl)-9(10H)-anthracenone), a selective KCNQ channel blocker. Furthermore, acute stress decreased the phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9 in the hippocampus, and flupirtine inhibited the reduction. These results suggest that the KCNQ/Kv7 channels may be a potential target for protecting both hippocampal synaptic plasticity and spatial memory retrieval from acute stress influences.

Effect of high-fat diet and antioxidants on hippocampal long-term potentiation in rats: An in vivo study

The objective of this study was to determine the relation between the chronic consumption of a high-fat diet (HFD) and antioxidants on long-term potentiation (LTP) in dentate gyrus (DG) of the adult rat hippocampus in vivo. Forty adult male Wistar rats were randomly assigned into five groups (N=6–8): control group consumed an ordinary diet; HFD group received HFD only; ANO group received HFD plus antioxidants; RHFD group received a restricted HFD (30% less fat than the HFD group); and RANO group received restricted HFD plus antioxidants. Following 6 months of controlled diets in each experimental group, the rats were anesthetized with intraperitoneal injection of ketamine and xylazin (100 and 2.5mg/kg, respectively), and placed into a stereotaxic apparatus for surgery, electrode implantation and field potential recording. The population spike (PS) amplitude and slope of excitatory post synaptic potentials (EPSP) were measured in DG area of adult rats in response to stimulation applied to the perforant pathway (PP) by 400Hz tetanization. The results showed that HFD decreased EPSP slope and PS amplitude with respect to the control group, whereas antioxidants increased these parameters compared to the control group. It was suggested that chronic HFD consumption can impair hippocampal LTP in the granular cells of the DG, and antioxidant supplementation reverses the impairment of synaptic plasticity induced in DG.

Improvement in Memory and Brain Long-term Potentiation Deficits Due to Permanent Hypoperfusion/Ischemia by Grape Seed Extract in Rats.

Cerebral hypoperfusion/ischemia (CHI) is a neurological disease where impaired hippocampus electrical activity and cognition caused by a serial pathophysiological events. This study aimed to evaluate the effects of chronic oral administration of grape seed extract (GSE) on passive avoidance memory and long-term potentiation (LTP) after permanent bilateral common carotid arteries occlusion (2CCAO) in male adult rats. Thirty-two adult male Wistar rats were randomly divided into: 1) Sham+Veh, 2) Isch+Veh, 3) Sham+GSE, 4) Isch+GSE. In order to make 2CCAO as an animal model of CHI, carotid arteries were ligatured and then cut bilaterally. To evaluation of passive avoidance memory, step-down latency (STL) was measured and LTP was recorded from hippocampal dentate gyrus (DG) after high frequency stimulation (HFS) in all rats. We found that memory was significantly impaired in rats after CHI (P<0.001) concomitant with hippocampal LTP inhibition (P<0.05, P<0.01 for LTP1 and LTP48 respectively). GSE treatment significantly improved memory impairment and increased hippocampal LTP in rats with 2CCAO. Our results in present study suggest that GSE exhibits therapeutic potential for short-and long-term memories as well as LTP in DG, which is most likely related at least in part to its antioxidative and free radical scavenging actions.

Aluminium-Maltolate-induced Impairment of Learning, Memory and Hippocampal Long-term Potentiation in Rats

Recently, aluminium (Al) has been proposed to be one of the environmental factors responsible for cause Alzheimer's disease (AD). However, the relationship between Al and AD is controversial. To investigate the effects of subchronic Aluminium-maltolate (Al (mal)(3)) exposure on the behavioral, electrophysiological functions. Forty Sprague-Dawley (SD) rats were randomly distributed into five groups. Over two months, rats in the saline group received daily intraperitoneal (i.p.) injections 0.9% saline, rats in the maltolate group received 7.56 mg/kg maltolate, and rats in the 0.27, 0.54, 1.08 mg/kg Al (mal)(3) groups received i.p. administrations of these three doses, respectively. Neural behavior was assessed in Morris water maze. Long-term potentiation (LTP) in hippocampus was recorded. Al content in the neocortex was determined using a graphite furnace atomic absorption spectrophotometer. Our studies indicate that subchronic Al (mal)(3) exposure significantly impaired spatial learning and memory abilities, suppressed the LTP in the CA1 hippocampal area, and elevated Al levels in cerebral cortex in a dose-dependent fashion. In conclusion, low doses of Al (mal)(3) can still lead to dramatic Al accumulation in the brain, severely impair learning and memory capacities, and hippocampal LTP.

Acutely applied MDMA enhances long-term potentiation in rat hippocampus involving D1/D5 and 5-HT2 receptors through a polysynaptic mechanism

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a drug of abuse that induces learning and memory deficit. However, there are no experimental data that correlate the behavioral evidence with models of synaptic plasticity such as long-term potentiation (LTP) or long-term depression (LTD). Using field potential recordings in rat hippocampal slices of young rats, we found that acute application of MDMA enhances LTP in CA3–CA1 synapses without affecting LTD. Using specific antagonists and paired-pulse facilitation protocols we observed that the MDMA-dependent increase of LTP involves presynaptic 5-HT2 serotonin receptors and postsynaptic D1/D5 dopamine receptors. In addition, the inhibition of PKA suppresses the MDMA-dependent increase in LTP, suggesting that dopamine receptor agonism activates cAMP-dependent intracellular pathways. We propose that MDMA exerts its LTP-altering effect involving a polysynaptic interaction between serotonergic and dopaminergic systems in hippocampal synapses. Our results are compatible with the view that the alterations in hippocampal LTP could be responsible for MDMA-dependent cognitive deficits observed in humans and animals.

Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats

Lead (Pb) exposure during development has been associated with impaired long-term potentiation (LTP). Hypothyroidism happening upon subjects with occupational exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis, leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis. Hippocampus is one of the targets of Pb exposure, and is sensitive to and dependent on thyroid hormones, leading us to explore whether levothyroxine (L-T 4) administration could alter the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb exposure. Our results show that Pb exposure caused a decrease in triiodothyronine (T 3) and tetraiodothyronine (T 4) levels accompanied by a dramatic decrease of TSH and application of L-T 4 restored these changes to about control levels. Hippocampal and blood Pb concentration were significantly reduced following L-T 4 treatment. L-T 4 treatment rescued the impairment of LTP induced by the Pb exposure. These results suggest that Pb exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a direct electrophysiological proof that L-T 4 relieves chronic Pb exposure-induced impairment of synaptic plasticity.

The Complement Control-Related Genes CSMD1 and CSMD2 Associate to Schizophrenia

Patients with schizophrenia often suffer from cognitive dysfunction, including impaired learning and memory. We recently demonstrated that long-term potentiation in rat hippocampus, a mechanistic model of learning and memory, is linked to gene expression changes in immunity-related processes involved in complement activity and antigen presentation. We therefore aimed to examine whether key regulators of these processes are genetic susceptibility factors in schizophrenia. Analysis of genetic association was based on data mining of genotypes from a German genome-wide association study and a multiplex GoldenGate tag single nucleotide polymorphism (SNP)-based assay of Norwegian and Danish case-control samples (Scandinavian Collaboration on Psychiatric Etiology), including 1133 patients with schizophrenia and 2444 healthy control subjects. Allelic associations were found across all three samples for eight common SNPs in the complement control-related gene CSMD2 (CUB and Sushi Multiple Domains 2) on chromosome 1p35.1-34.3, of which rs911213 reached a statistical significance comparable to that of a genome wide threshold (p value = 4.0 × 10(-8); odd ratio = .73, 95% confidence interval = .65-.82). The second most significant gene was CSMD1 on chromosome 8p23.2, a homologue to CSMD2. In addition, we observed replicated associations in the complement surface receptor CD46 as well as the major histocompatibility complex genes HLA-DMB and HLA-DOA. These data demonstrate a significant role of complement control-related genes in the etiology of schizophrenia and support disease mechanisms that involve the activity of immunity-related pathways in the brain.

Individual and combined effects of beta-amyloid1-42, donepezil and haloperidol on long-term potentiation in rat hippocampus

Event Abstract Back to Event Individual and combined effects of beta-amyloid1-42, donepezil and haloperidol on long-term potentiation in rat hippocampus Elena Solntseva1* and Nadezhda Kapai1 1 Center of Neurology RAMS, Russia Donepezil is a potent acetylcholinesterase inhibitor used for the treatment of Alzheimer’s disease (AD). Additional therapeutically relevant target for donepezil is sigma1 receptors (Kato et al., 1999). It is generally believed that beta-amyloid peptides (Abeta) contribute to the pathogenesis of AD. Low concentrations of Abeta were shown to impair long-term potentiation (LTP) in hippocampus (Chen et al., 2000). It was shown in our previous work that donepezil in concentration of 1 microM antagonizes the suppressive action of Abeta1-42 on LTP in rat hippocampal slices. We suppose that sigma1 receptors might be involved into mechanism(s) of this effect of donepezil. The purpose of present study was to determine whether donepezil-induced reversal of LTP impaired by Abeta can be abolished by haloperidol, a potent antagonist of sigma1 receptors (Hayashi & Su, 2008). In the control group, the amplitude of population spikes (PS) 30 min post-tetanus reached 146±11% (n = 10). Neither 1 microM donepezil (n = 6), nor 0,5 microM haloperidol (n = 5) changed LTP significantly. Abeta1-42 (200 nM) markedly suppressed the LTP induction or even caused the depression of PS: the amplitude of PS 30 min post-tetanus was 82 ± 15% (p < .005, n = 7). This suppression of LTP could be markedly prevented when donepezil was co-administered with Abeta: the amplitude of PS 30 min post-tetanus was 136 ± 11% (p < .05, n = 5). Further, we co-administered three substances: Abeta, donepezil and haloperidol, and have found that haloperidol antagonizes the stimulating action of donepezil on LTP: the amplitude of PS 30 min post-tetanus was 92 ± 6% (p < .05, n = 5). Results suggest the involvement of sigma1 receptors into mechanisms of the rescue of hippocampal LTP impaired by Abeta by donepezil. Funding: Supported by grant from Russian Foundation for Basic Research. Keywords: AD, Neuropsychiatry Conference: XI International Conference on Cognitive Neuroscience (ICON XI), Palma, Mallorca, Spain, 25 Sep - 29 Sep, 2011. Presentation Type: Poster Presentation Topic: Poster Sessions: Neuropsychiatric Applications Citation: Solntseva E and Kapai N (2011). Individual and combined effects of beta-amyloid1-42, donepezil and haloperidol on long-term potentiation in rat hippocampus. Conference Abstract: XI International Conference on Cognitive Neuroscience (ICON XI). doi: 10.3389/conf.fnhum.2011.207.00226 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 21 Nov 2011; Published Online: 28 Nov 2011. * Correspondence: Dr. Elena Solntseva, Center of Neurology RAMS, Moscow, Russia, soln@front.ru Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Elena Solntseva Nadezhda Kapai Google Elena Solntseva Nadezhda Kapai Google Scholar Elena Solntseva Nadezhda Kapai PubMed Elena Solntseva Nadezhda Kapai Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The new pyridoindole antioxidant SMe1EC2 and its intervention in hypoxia/hypoglycemia-induced impairment of long-term potentiation in rat hippocampus

Previously, the pyridoindole SMe1EC2 was proved to inhibit lipoperoxidation and carbonylation of proteins in rat brain cortex in the system Fe2+/ascorbate and improvement of resistance of the rat hippocampus was reported against ischemic conditions in vitro (hypoxia/hypoglycemia) expressed by the enhanced neuronal response recovery in reoxygenation. The hippocampus fulfils many of the criteria for a neuronal correlate of learning and memory. Recently, an impairment of hippocampal long-term potentiation (LTP) was reported under oxidative stress. Different therapies, including antioxidants, have been studied intensively concerning the impairment of neuronal plasticity. In this study marked reduction of LTP, elicited by a single burst (100 Hz, 1s) in the CA3-CA1 area of rat hippocampal slices, was shown due to transient hypoxia/hypoglycemia compared to control slices. On the basis of previously reported antioxidant and neuroprotective effects of SMe1EC2, its effect on loss of LTP in the hippocampus due to ischemic conditions was studied in vitro. The pyridoindole tested improved hypoxia/hypoglycemia-induced reduction of LTP compared to untreated hypoxic slices. An opposite effect of SMe1EC2 on LTP induction was found in control slices. The mechanism of SMe1EC2 action on LTP in ischemic conditions has been suggested to differ from the mechanism of its effect in “normoxia” and may be due to different redox status in control and ischemic brain tissue. The manifested LTP-protective effect of SMe1EC2 observed in the rat hippocampus exposed to ischemia in vitro may find exploitation in therapy associated with injured neuronal plasticity in some conditions, including ischemia, trauma and aging in man.

Cocaine withdrawal enhances long-term potentiation in rat hippocampus via changing the activity of corticotropin-releasing factor receptor subtype 2

The neural plasticity mechanisms that underlie learning and memory may also be engaged when drug addiction occurs. It was reported that long-lasting neuroadaptations induced by cocaine use and withdrawal require the participation of hippocampus. However, the role of corticotrophin-releasing factor receptors in this process remains unclear. In the present study, the effects of chronic cocaine treatment (a 14-day cocaine administration, 20 mg/kg i.p., daily) and short-term cocaine withdrawal (a 3-day cocaine extinction following a 14-day cocaine administration) on long-term potentiation (LTP), one prominent cellular mechanism for learning and memory, were assessed in the CA1 region of the rat hippocampal slices. We found that cocaine withdrawal, but not the chronic cocaine administration itself, significantly enhanced the magnitude of LTP in hippocampal slices, as compared with that in saline controls. Selective blockade of corticotrophin-releasing factor receptor subtype 1 (CRF 1) with the specific antagonist NBI 27914 (100 nM in vitro) attenuated the magnitude of LTP in hippocampal slices from cocaine withdrawal rats, and intriguingly, also from saline control rats, while specific blockade of corticotrophin-releasing factor receptor subtype 2 (CRF 2) with astressin2-B (100 nM in vitro) selectively attenuated the magnitude of LTP in hippocampal slices from cocaine withdrawal rats. Our data suggest that short-term cocaine withdrawal treatment may cause synaptic plasticity in hippocampus partially via changing the activity of CRF 2 in the hippocampus.