Potentiation Research Articles

Correction: Potentiation of polycyclic aromatic hydrocarbon uptake in zebrafish embryos by nanoplastics

Correction for ‘Potentiation of polycyclic aromatic hydrocarbon uptake in zebrafish embryos by nanoplastics’ by Yueyang Zhang et al., Environ. Sci.: Nano, 2020, 7, 1730–1741, DOI: 10.1039/D0EN00163E.

Enteral Antibiotics Stimulate Small Intestinal Mucosal Growth in Mice and May Act Synergistically with the Serotonin Signaling System

Background: The intestinal microbiome participates in numerous mucosal processes with previous work demonstrating intestinal mucosal growth in gnotobiotic mice. Others have suggested that certain indigenous gut bacteria are capable of stimulating host serotonin synthesis. Furthermore, potentiation of serotonin signaling has been shown to enhance small intestinal mucosal growth in mice. Thus, we hypothesized that altering the microbiome with enteral antibiotics would enhance small intestinal mucosal growth …

Effect of continuous environmental enrichment and aerobic exercise on rat plasma and hippocampal brain-derived neurotrophic factor

Objective: Environmental enrichment (EE) or exercise can positively affect memory function through increased long-term potentiation and neurogenesis, which is facilitated by brain-derived neurotrophic factor (BDNF). BDNF promotes blood vessel growth, angiogenesis linked to adult neurogenesis, and neuronal survival. Here, we investigated the effects of EE, aerobic exercise, and their combination on plasma and hippocampal BDNF levels. Materials and Methods: Twenty-four 7-month-old adult male Wistar rats weighing 300–400 g were randomly assigned to the following four groups: control (C), aerobic exercise (A), EE, and combined EE and aerobic exercise (EEA). Interventions were given for 8 weeks, and plasma and hippocampal BDNF levels were measured using enzyme-linked immunosorbent assay. Results: A combination of aerobic exercise and continuous EE produced the largest increase in hippocampal and plasma BDNF levels in adult rats. A positive correlation (r = 0.686, P = 0.002, n = 24) was observed between plasma and hippocampal BDNF levels in adult rats. Conclusion: We conclude that a combination of aerobic exercise and continuous EE increases plasma and hippocampal BDNF in adult rats.

The role of perivascular adipose tissue and endogenous hydrogen sulfide in vasoactive responses of isolated mesenteric arteries in normotensive and spontaneously hypertensive rats.

Perivascular adipose tissue (PVAT) and hydrogen sulfide (H2S) play important roles in the modulation of vasoactive responses and can interfere with the ethiopathogenesis of essential hypertension. The aim of this study was to evaluate the mutual relationship between PVAT and H2S (endogenously produced, exogenous) in vasoactive responses of isolated mesenteric arteries (MA) in adult normotensive (Wistar) and spontaneously hypertensive rats (SHR). In SHR, hypertension was associated with cardiac hypertrophy and increased contractility; however, there were no differences in the amount of retroperitoneal fat between strains. PVAT revealed the anti-contractile effect on vasoconstriction induced by exogenous noradrenaline in both strains, but surprisingly, this effect was stronger in SHR. Concurrently; PVAT exhibited a pro-contractile effect on contractions to endogenous noradrenaline released from arterial sympathetic nerves in SHR, but not in Wistar rats. We confirmed the anti-contractile effect of H2S in both, the vascular wall and PVAT of Wistar rats because the pre-treatment with propargylglycine (PPG), an inhibitor of H2S producing enzyme, significantly increased the noradrenaline-induced contraction. In SHR, H2S in the vascular wall exhibited a pro-contractile effect that was eliminated by the presence of PVAT; however, the pre-treatment with PPG did not affect noradrenaline contraction farther. Nevertheless, unlike in Wistar rats, the presence of PVAT potentiated the vasorelaxant effect of exogenously applied H2S in SHR. Our results confirmed that PVAT of MA and endogenously produced H2S could manifest as pro-contractile or as anti-contractile. In SHR, unlike in Wistar rats, the pro-contractile effect of PVAT associated with the stimulation of perivascular nerves, and the pro-contractile effect of H2S in the arterial wall could represent pathologic features. On the other hand, PVAT of SHR is endowed with compensatory vasoactive mechanisms, which include stronger anti-contractile action of an unknown factor (other than H2S) and potentiation of the vasorelaxant effect of exogenous H2S.

Effect of Dl-3-n-butyphthalid on learning and memory deficiency and hippocampus synaptic long term potentiation in diabetic mice

Objective To study the effect and mechanism of Dl-3-n-butylphthalide(NBP) on memory and learning ability in type 2 diabetes model db/db mice. Methods Sixteen male db/db mice were randomly divided into the NBP group and diabetes group, with 8 mice in each group.Eight male db/m mice of the same age were treated as the control group. NBP group was given NBP by gavage, while diabetes group and control group were given equal volume vegetable oil by gavage. After 6 weeks treatment, Morris water maze was used to examine the spatial memory and learning ability of the mice in each group. The changes of long-term potentiation (LTP) in the hippocampus area of mice were detected by electrophysiological techniques. RT-PCR and Western blot were employed to measure expressions of VEGF, caspase-3, and Aβ1-42 in hippocampus of mice. Results Compared with the control group((21.49±4.41)s), average escape latency of day 5 in the diabetes group and NBP group were increased significantly ((51.69±5.45)s, (26.92±4.76)s, t=9.21, 2.35, both P<0.05). Compared with the control group(7.00±0.60), the number of crossing the target platform in the diabetes group and NBP group were decreased significantly(2.34±0.27), (4.95±0.54), t=-6.56, -2.49; both P<0.05). Compared with the control group((255.90±54.24)%), LTP level in hippocampus of the diabetes group and NBP group were significantly decreased(130.97±14.08)%, (176.17±18.96)%, t=-4.25, -2.38; both P<0.05). The relative expression of VEGF, caspase-3, and Aβ1-42 in the diabetes group and NBP group were significantly increased compared with those of the control group (t=4.59, 8.42; 7.36, 3.85; 3.84, 2.11; all P<0.05). Compared with the diabetes group, the escape latency of day 5, the number of crossing the target platform and LTP level were improved in the NBP group (t=-7.25, 4.06, 3.25; all P<0.05). The decreased expression of caspase-3, Aβ1-42 and increased expression of VEGF were reversed after NBP treatment in db/db mice (t=-4.14, -2.31, 3.42; all P<0.05). Conclusion NBP might improve cognitive function and LTP by exerting anti-apoptosis effect through inhibiting the deposition of Aβ1-42 and upregulating VEGF expression in hippocampus of db/db mice. Key words: Type 2 diabetes mellitus; Cognitive function; Dl-3-n-Butyphthalide; VEGF; Aβ1-42; Mice

Stimulation of regenerative blastema formation in lizards as a model to analyze limb regeneration in amniotes.

The hypothesis here presented tries to explain why organ regeneration is present in fish and amphibians (anamniotes) but is absent in reptiles, birds and mammals (amniotes). Anamniotes possess complex life cycles including larvae and metamorphosis stages, the latter representing a physiological form of organ destruction and regeneration coded in their genome that can be reactivated in adults in the form of regeneration. Part of the genome for larvae and metamorphosis phases was likely lost in amniotes with the evolution of direct development, the potentiation of the immune system and the increase in complexity of the nervous system. These events consequently determined incapability for organ regeneration in extant amniotes with the exception of the lizard tail. This likely derives from the evolution of a mechanism of immunosuppression that allows the regeneration of the tail although the complete morphogenetic plane of tail embryogenesis is lost. The lizard model of imperfect but outstanding organ regeneration indicates the possibility to improve organ regeneration also in other amniotes. In fact, the induction of a blastema in the amputated lizard limb has stimulated the formation of short limbs containing cartilaginous bones of the femur, tibia and fibula, and these experiments foster some hope for future attempts to induce limb and digit regeneration also in mammals.

Pain research and clinical transformation based on synaptic plasticity

Pain is a complicated physiological and psychological activity, which is always accompanied by various diseases. It has become an urgent problem to be solved because of its flexible etiology and complex mechanisms. This article mainly elaborates the progress of research on synaptic plasticity remodeling in pain, introduces the transduction and synaptic plasticity of pain signals, the role of synaptic structure and functional plasticity in pain, and review the treatment of pain based on synaptic plasticity. The aim of this review is to better understand the mechanism of pain, provides a novel idea for its subsequent treatment, and gives more reliable evidence for clinical pain treatment. Key words: Pain; Spinal cord; Anterior cingulate cortex; Synaptic plasticity; Dendritic spine; Long-term potentiation; Long-term depression

Post-activation potentiation and the shot put throw

Acute post activation potentiation (PAP) is a physical conditioning activity that incorporates intense muscle activation to enhance muscular force production. Practical applications of PAP as a conditioning activity to enhance sport performance are of interest to athletes and coaches. PURPOSE: This study compared the effects of a dynamic warm-up and a dynamic warm-up followed by a PAP conditioning activity on shot put throw distance. METHODS: NCAA Division I male (n=6) and female (n=7) track and field athletes volunteered as participants for the study. The study employed a randomized repeated measures crossover design where each participant was randomly placed into one of two groups. During the first test session one group performed a dynamic warm-up followed by an 8-minute rest period then a shot put throw test. The other group performed a dynamic warm-up followed by a PAP conditioning activity comprised of 3 repetitions of a hang clean and jerk at 80% 1-RM followed by an 8-minute rest period then a shot put throw test. During week 2 the two groups crossed over with respect to the warm-up conditions and repeated the shot put throw test. Three shot put trials were collected following each warm-up condition and the best score was used for subsequent analysis. The shot put throw distances were compared between warm-up strategies with a paired t-test. RESULTS: The shot put throw scores were: PAP 10.93±1.81* and non-PAP 10.57±1.84 meters (p=0.007). CONCLUSION: Within the parameters of this study, when compared to a standard dynamic warm-up, a dynamic warm-up strategy that includes a PAP event significantly improves shot put throw performance. Coaches and athletes could apply the dynamic warm-up that includes a PAP conditioning activity as implemented in this study to enhance shot put performance during competitive scenarios.

The critical roles of synaptic plasticity in opioid addiction

Background Opiates are widely used for treatment of chronic pain. It is noteworthy that its long-term application and abuse lead to addiction, a serious public health and social problem. Objective To review the roles of synaptic plasticity in the development and maintenance of opioid addiction. Content Synaptic plasticity is one of the major cellular events in the development of drug-addiction. Structurally, synaptic plasticity involves synapse formation, pruning, redistribution, and modification, and functionally it manifests as long-term potentiation(LTP) or long-term depression(LTD) of synaptic transmission. Chronic exposure to morphine was reported to modify synapses in the ventral tegmental area, the nucleus accumbens, the prefrontal cortex, the amygdala, and the hippocampus, probably through activating cycline-dependent kinase-5, which leads to the accumulation of FosB. The enhancement of LTP in the hippocampus in morphine addicted animals is concurred with upregulation of N-methyl-D- aspartate receptors(NMDAR) and GluR2-containing α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors(AMPAR). These molecular events could be caused by dopamine receptor activation and epigenetic modulation. Synaptic plasticity may be related to behavioral phenotypes of morphine addiction, such as, enhanced locomotion, stereotypic behaviors, and drug seeking and intake behavior. Trend Further investigations are warranted to clarify whether synaptic plasticity in certain brain region(s) corelates with particular behavioral aspect(s) of morphine addiction. Location-specific disruption of synaptic plasticity could be new therapeutic strategies for opioid addiction. Key words: Synaptic plasticity; Opiate; Addiction

Mechanism and research advances of isoflurane on cognitive impairment in young rats

Background Isoflurane is an inhaled anesthetic widely used in pediatric and obstetric operations, due to its advantages such as anesthesia depth which is easy to control and little influence on the circulation. Objective Recent reports showed that repeated or long-time exposure to anesthetics at the young stage may cause deficient memory in the future. Therefore, increasing attentions have been drawn on isoflurane's mechanism about neurological damages. Content This paper summarized the toxic mechanism of isoflurane in the recent five years, and synaptic plasticity damages can cause neurotoxicity, inhibit N-methyl-D-aspartate(NMDA) receptor and stimulate amino acid type A receptor (GABAAR) and affect long-term potentiation, calcium homeostasis, and activate neurotrophins to produce apoptotic pathway, and other possible toxic mechanisms. Trend This paper can further determine the research direction, providing references for transform of basic research data into clinical practice as well as for the research and development of new protective drugs. Key words: Isoflurane; Developmental brain; Apoptosis; Neurotoxicity; Synapsis

Unseeded Cavitation with Confocal Ultrasound for the Potentiation of Doxorubicin

Unseeded Cavitation with Confocal Ultrasound for the Potentiation of Doxorubicin

Potentiation of Disinfectant Efficiency of Different Dilutions of Ethanol, Bleach and Phenolics against Pseudomonas Aeruginosa and Staphylococcus Aureus

Ethanol, Bleach and Phenolics are three kinds of disinfectants which have been widely used in common laboratories. In this study, a compared experiment on these three disinfectants efficiency was conducted against Staphylococcus aureus and Pseudomonas aeruginosa using agar hole diffusion method. Different concentrations of bleach (1%, 2%, 3%, 4% and 5%) were used on both organisms. Also (50%, 60%, 70%, 85% and 95%) of ethanol as well as (5%, 10%, 20%, 25%, and 30%) Phenolics were used. Differences in concentrations tested was because, the original concentrations of the disinfectants differs. After 24 hours of incubation at 37 0 C, the results showed that all the disinfectants inhibited the growth of the test organism in their concentrated forms. The diameter of zone of inhibitions were measured around each well by using a ruler in millimeters, using different concentrations, their efficacies varied. The results showed that 30% Phenolics had the best efficiency against both test organisms and 5% bleach had a better effect on Staphylococcus aureus than Pseudomonas aeruginosa , while ethanol showed least sensitivity. 70% concentration gave the highest effect on Staphylococcus aureus as compared with Pseudomonas aeruginosa .

The role of the early growth response gene-1 in learning and memory process

Background The early growth response gene-1(Egr-1) is considered to be a triggering mechanism that maintains long term potentiation and activates neurogenesis. The expression of Egr-1 protein is closely associated with the consolidation, reconsolidation and extinction of long term memory. Objective Providing potential research targets for studying the mechanism and treatment of postoperative cognitive dysfunction. Content We review the structure, expression pattern of Egr-1 protein and its roles in learning and memory. Trend Egr-1 plays different roles in different phases of memory, but the specific signaling pathways and their relationship with postoperative cognitive dysfunction deserve further clarification. Key words: The early growth response gene-1; Signal pathway; Learning and memory

Effect of hypoxemia factor on hippocampal long-term potentiation in newborn rats undergoing propofol anesthesia

Objective To evaluate the effect of hypoxemia factor on hippocampal long-term potentiation(LTP)in newborn rats undergoing propofol anesthesia. Methods Forty-two pathogen-free healthy Sprague-Dawley rats(21 males, 21 females), aged 7 days, weighing 14-18 g, were divided into 3 groups(n=14 each)using a random number table: propofol plus air group(group PA), propofol plus pure oxygen group(group PO)and intralipid plus pure oxygen group(group IO). Propofol 50 mg/kg was injected intraperitoneally once a day for 7 consecutive days in PA and PO groups. Intralipid 5.0 ml/kg was injected intraperitoneally once a day for 7 consecutive days in IO group. The rats were exposed to air or pure oxygen for 6 h after the end of each injection. The arterial oxygen saturation and respiratory rate were determined after administration. The rats were returned to the cage after recovery of righting reflex. Six rats in each group were selected for preparation of hippocampal slices at 24 h after the last injection on 7th day, and the electric stimulation-induced field excitatory post synaptic potential(fEPSP)and success rate of LTP induction were recorded. Morris water maze test was performed in the other rats at 2 weeks after administration to assess the cognitive function. Results Compared with group IO, the respiratory rate, amplitude of fEPSP and success rate of LTP induction were significantly decreased, and the escape latency was prolonged in group PO(P<0.05). Compared with group PO, the arterial oxygen saturation, amplitude of fEPSP and success rate of LTP induction were significantly decreased, the escape latency was prolonged, and the number of crossing the original platform was decreased in group PA(P<0.05). Conclusion Hypoxemia factor increases propofol-induced neurotoxicity in the central nervous system of newborn rats. Key words: Oxygen; Propofol; Hippocampus; Long-term potentiation; Cognition

β-caryophyllene and low-doses of doxorubicin against liver cancer cells: a “metronomic chemotherapy”

Cholangiocarcinoma and hepatocellular carcinoma are primary liver cancers, both representing a growing challenge due to their increasing morbidity and mortality. A “metronomic chemotherapy”, consisting of the repeated administration of low and/or continuous doses of anti-neoplastic drugs, represents an alternative approach to the standard chemotherapy [1]. Numerous natural substances exhibited in vitro chemosensitizing features: in particular, the natural sesquiterpene β-caryophyllene (CRY) has been proved to increase the cytotoxicity of doxorubicin (DOXO) in leukemic cells [2]. Hence, our aim has been to evaluate the ability of CRY to enhance the efficacy of low-dose DOXO in human liver cancer cells, by applying a metronomic protocol. To this end, human liver HepG2 and CCA cells have been used as models of hepatocellular carcinoma and cholangiocarcinoma. The metronomic protocol was based on a 2h low-time exposition to the test substances, followed by 72h incubation for restoring. This scheduling has been applied 3 times and cytotoxicity was measured by MTT assay. Both the substances alone (CRY 1-100 μg/ml; DOXO 1-500 μg/ml) and the combination of DOXO with a nontoxic concentration of CRY were assessed. We found that the repeated treatments with low concentrations produced a significant potentiation (about 30 %) of DOXO cytotoxicity in HepG2. The combination with CRY increased the DOXO activity, reaching a 70 % inhibition of cell viability at 50 μg/ml after 2 repeated treatments. Similar effects were found in CCA, although repeated treatments induced no additional potentiation. These results highlight a possible role of CRY as a chemosensitizing agent for DOXO-based chemotherapy of liver cancer.

A reversible carnitine palmitoyltransferase I (CPT1) inhibitor offsets chronic lymphocytic leukemia cell proliferation

Crucial for CLL development and progression are iterative cycles of cell re-activation and proliferation in lymphoid tissues. Since cellular fatty acid (FA) import and oxidation (FAO) were recently reported to be upregulated in CLL, we explored in-vitro effects of ST1326, a reversible inhibitor of carnitine-palmitoyl transferase 1A (CPT1A), on leukemic cells subject to activating microenvironment-mimicking stimuli. ST1326 induced dose-dependent mitochondrial dysfunction and cell death, which were remarkably higher in activated/proliferating than quiescent CLL cells. Drug sensitivity was observed irrespective of the presence of TP53 alterations or chromosomal abnormalities. ST1326 cytotoxicity was associated with decreased levels of intracellular acetylCoA and phosphorylated STAT3, known to favor CLL cell proliferation and upregulate antiapoptotic Bcl-2 family members. Indeed, rising of Mcl-1 and Bcl-xl expression in response to microenvironment stimulation was impaired by ST1326. Drug combination experiments with the BH3-mimetic ABT-199/Venetoclax, whose effects are counteracted by Mcl-1/Bcl-xl and cell proliferation, showed strong ST1326-mediated potentiation of ABT-199 cytotoxicity in activated/proliferating CLL cells. The data indicate that CLL cells turning to an activated/proliferating state become more dependent on FAO and more sensitive to FAO-antagonists, and pave the way for ST1326 as an adjuvant tool in anti-CLL drug-combination regimens with drugs that loose efficacy on proliferating leukemic cells.

Effects of Isopimaric Acid on cognitive handicap and synaptic plasticity in APP/PS1 mice

Objective To investigate the protective effects of isopimaric acid (ISO), the BKCa channel activator, on cognitive function and synaptic plasticity in APP/PS1 mice. Methods Alzet osmotic pump was loaded with ISO or DMSO only and assembled with ALZET Brain Infusion Kit III. The cannula was implanted into the lateral ventricle of 4-month-old male APP/PS1 mice or matched wild type (WT) mice. Two weeks later, open field test and Morris water maze were conducted. Paired-pulse facilitation (PPF) and TBS-induced long-term potentiation (LTP) were recorded in CA1 region of hippocampus. Results The open field test showed that there was no significant difference among the four groups in spontaneous activities and vertical plane movement distance within 30 minutes. Floor plane movement distance was significantly greater in APP/PS1+ DMSO group than that in WT+ DMSO group(P<0.05). Compared with the WT+ DMSO group, APP/PS1+ DMSO group had significantly longer escape latency from the third to fifth day and lower percentage of time spent in the target quadrant ((43.27±3.24)% vs (34.19±2.56)%) and the number of crossing through the platform ((4.25±0.66)times vs (1.93±0.33)times)(P<0.05). Compared with the APP/PS1+ DMSO group, the APP/PS1+ ISO group had significantly shorter escape latency from the fourth to fifth day and higher percentage of time spent in the target quadrant ((46.16±3.51)%) and the number of crossing through the platform ((3.41±0.34) times) (P<0.05). PPF in APP/PS1+ DMSO group significantly reduced compared with that in WT+ DMSO group at 30-50ms interstimulus interval(P<0.05). PPF in APP/PS1+ ISO group((224.50±13.79)%) was significantly augment compared with APP/PS1+ DMSO ((174.99±6.68)%) group at 40 ms interstimulus interval (P<0.05). The LTP at 60 min post-TBS was significantly smaller in the APP/PS1+ DMSO group ((135.19±1.32)%) than that in the WT+ DMSO group ((172.17±4.15)%)(P<0.001). The LTP of the APP/PS1+ ISO group((160.48±1.19)%) became significantly increased compared with that in the APP/PS1+ DMSO group(P<0.001). Conclusion BKCa channel activator ISO improve the learning and memory function of APP/PS1 mice by promoting PPF and increasing LTP to recover synaptic plasticity in the hippocampus. Key words: Alzheimer’s disease; APP/PS1; Isopimaric acid; Synaptic plasticity; BKCa channel

Potentiation of TRPM5 leads to increased taste perception and insulin secretion

Potentiation of TRPM5 leads to increased taste perception and insulin secretion

An enriched environment enhances synaptic plasticity and cognition post-stroke

Objective To observe the effects of an enriched environment (EE) on cognitive functioning and the synaptic plasticity of mice modeling post-stroke cognitive impairment (PSCI) and explore the possible mechanisms involved. Methods Mice modeling PSCI and sham-operated mice were randomly divided into 3 groups: sham-operated mice in a standard environment (the Sham+ SE group), PSCI mice in a standard environment (the PSCI+ SE group) and PSCI mice in an enriched environment (the PSCI+ EE group). The cognitive functioning of all of the mice was quantified using a Morris water maze and their hippocampal long-term potentiation (LTP) was recorded using an electrophysiological method. The level of synaptophysin was detected using Western blotting. Synaptic ultrastructure in the hippocampus was imaged using electron microscopy. Results Compared with the Sham+ SE group, the PSCI+ SE group showed significantly poorer water maze performance and failed induction of contralateral LTP. Their average level of synaptophysin was significantly lower, and significant adverse changes in the synaptic ultrastructure of the hippocampus were observed, including a decreased number of synapses. The average width of the synaptic cleft, postsynaptic density and the interface curvature of the synapses were all less desirable. All of the measurements of the PSCI+ EE group improved significantly compared to those of the PSCI+ SE group, but were still significantly poorer than those of the Sham+ SE group. Conclusions An enhanced environment can improve the cognitive functioning of mice modelling PSCI. It may be that an EE can improve synaptic plasticity in the hippocampus contralateral to the stroke. Key words: Stroke; Cognitive impairment; Enriched environments; Synaptic plasticity

A PARP1-Erk2 synergism is required for stimulation-induced expression of immediate early genes.

A PARP1-Erk2 synergism was required to generate synaptic long-term potentiation in the CA3-CA1 hippocampal connections. This molecular mechanism was associated with the recently identified pivotal role of polyADP-ribosylation in learning. High frequency electrical stimulation of cortical and hippocampal neurons induced binding of phosphorylated Erk2 (transported into the nucleus) to the nuclear protein PARP1. PARP1-Erk2 binding induced PARP1 activation and polyADP-ribosylation of its prominent substrate, linker histone H1. A facilitated access of PARP1-bound phosphorylated Erk2 to its substrates, transcription factors Elk1 and CREB was attributed to the release of polyADP-ribosylated H1 from the DNA, causing local DNA relaxation. Erk-induced phosphorylation of transcription factors activating the HAT activity of CBP (CREB binding protein), recruited acetylated histone H4 to the promoters of immediate early genes (IEG) cfos, zif268 and arc, which are implicated in synaptic plasticity. In accordance, their induced expression was suppressed after PARP1 genetic deletion in PARP1-KO mice, or after PARP1 inhibition or silencing. Moreover, under these conditions, long-term synaptic potentiation (LTP) (indicating synaptic plasticity) was not generation in the hippocampal CA3-CA1 connections, and learning abilities were impaired. Furthermore, both IEG expression and LTP generation failed when cerebral neurons accumulated single strand DNA breaks, due to a predominant binding of PARP1 to nicked DNA, occluding its Erk binding sites. Thus, a declined synaptic plasticity is anticipated when aged cerebral neurons accumulate DNA single-strand breaks during life span.