Crotamine derived from Crotalus durissus terrificus venom combined with drugs increases in vitro antibacterial and antifungal activities.

This study investigated crotamine (CTA), a peptide derived from the venom of the South American rattlesnake Crotalus durissus terrificus, known for its exceptional cell penetration potential. The objective was to explore the antibacterial and antifungal activity of CTA, its ability to inhibit efflux pumps and evaluate the effectiveness of its pharmacological combination with antibiotics and antifungals. In microbiological assays, CTA in combination with antibiotics was tested against strains of S. aureus and the inhibition of NorA, Tet(K) and MepA efflux pumps was also evaluated. CTA alone did not present clinically relevant direct antibacterial action, presenting MIC > 209.7 µM against strains S. aureus 1199B, IS-58, K2068. The standard efflux pump inhibitor CCCP showed significant effects in all negative relationships to assay reproducibility. Against the S. aureus 1199B strain, CTA (20.5 µM) associated with norfloxacin diluted 10 × (320.67 µM) showed a potentiating effect, in relation to the control. Against the S. aureus IS-58 strain, the CTA associated with tetracycline did not show a significant combinatorial effect, either with 2304 or 230.4 µM tetracycline. CTA at a concentration of 2.05 µM associated with ciprofloxacin at a concentration of 309.4 µM showed a significant potentiating effect. In association with EtBr, CTA at concentrations of 2.05 and 20.5 µM potentiated the effect in all strains tested, reducing the prevention of NorA, Tet(K) and MepA efflux pumps. In the C. albicans strain, a potentiating effect of fluconazole (334.3 µM) was observed when combined with CTA (2.05 µM). Against the C. tropicalis strain, a significant effect was also observed in the association of fluconazole 334.3 µM, where CTA 2.05 µM considerably reduced fungal growth and decreased the potentiation of fluconazole. Against the C. krusei strain, no significant potentiating effect of fluconazole was obtained by CTA. Our results indicate that CTA in pharmacological combination potentiates the effects of antibiotics and antifungal. This represents a new and promising antimicrobial strategy for treating a wide variety of infections.

A computational model elucidating mechanisms and variability in theta burst stimulation responses.

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (rTMS) with unknown underlying mechanisms and highly variable responses across subjects. To investigate these issues, we developed a simple computational model. Our model consisted of two neurons linked by an excitatory synapse that incorporates two mechanisms: short-term plasticity (STP) and spike-timing-dependent plasticity (STDP). We applied a variable-amplitude current through I-clamp with a TBS time pattern to the pre- and post-synaptic neurons, simulating synaptic plasticity. We analyzed the results and provided an explanation for the effects of TBS, as well as the variability of responses to it. Our findings suggest that the interplay of STP and STDP mechanisms determines the direction of plasticity, which selectively affects synapses in extended neurons and underlies functional effects. Our model describes how the timing, number, and intensity of pulses delivered to neurons during rTMS contribute to induced plasticity. This not only successfully explains the different effects of intermittent TBS (iTBS) and continuous TBS (cTBS), but also predicts the results of other protocols such as 10 Hz rTMS. We propose that the variability in responses to TBS can be attributed to the variable span of neuronal thresholds across individuals and sessions. Our model suggests a biologically plausible mechanism for the diverse responses to TBS protocols and aligns with experimental data on iTBS and cTBS outcomes. This model could potentially aid in improving TBS and rTMS protocols and customizing treatments for patients, brain areas, and brain disorders.

Selegiline Improves Cognitive Impairment in the Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurological disorder characterized by cognitive decline. This study was undertaken to evaluate the effects of selegiline (SEL) against AD-induced cognitive deficits and explore the possible involved mechanisms. AD was induced by unilateral intracerebroventricular (U-ICV) injection of 5 µg of amyloid beta1-42 (Aß1-42), and oral administration of SEL (0.5 mg/kg/day) was performed for 30 consecutive days. Aß injection resulted in spatial cognitive decline, as demonstrated by a decrease in the time spent in the target zone on the probe day (P < 0.01) in the Barnes maze test (BMT). This spatial cognitive decline was associated with disrupted synaptic plasticity, as indicated by reductions in both components of hippocampal long-term potentiation (LTP), namely population spike amplitude (P < 0.001) and field excitatory postsynaptic potential (P < 0.001). On the other hand, the injection of Aß resulted in oxidative stress by decreasing total thiol group (TTG) content and increasing malondialdehyde (MDA) levels in the rat plasma (P < 0.001). Additionally, the number of healthy cells in the hippocampal dentate gyrus (DG) and CA1 regions was reduced in AD rats (P < 0.001). However, oral administration of SEL improved spatial cognitive decline in the Aß-induced AD rats. The results suggest that improvement of neuroplasticity deficiency, regulation of oxidant/antioxidant status, and suppression of neuronal loss by SEL may be the mechanisms underlying its beneficial effect against AD-related spatial cognitive impairment.

Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modeling.

Schizophrenia phenotypes are suggestive of impaired cortical plasticity in the disease, but the mechanisms of these deficits are unknown. Genomic association studies have implicated a large number of genes that regulate neuromodulation and plasticity, indicating that the plasticity deficits have a genetic origin. Here, we used biochemically detailed computational modeling of postsynaptic plasticity to investigate how schizophrenia-associated genes regulate long-term potentiation (LTP) and depression (LTD). We combined our model with data from postmortem RNA expression studies (CommonMind gene-expression datasets) to assess the consequences of altered expression of plasticity-regulating genes for the amplitude of LTP and LTD. Our results show that the expression alterations observed post mortem, especially those in the anterior cingulate cortex, lead to impaired protein kinase A (PKA)-pathway-mediated LTP in synapses containing GluR1 receptors. We validated these findings using a genotyped electroencephalogram (EEG) dataset where polygenic risk scores for synaptic and ion channel-encoding genes as well as modulation of visual evoked potentials were determined for 286 healthy controls. Our results provide a possible genetic mechanism for plasticity impairments in schizophrenia, which can lead to improved understanding and, ultimately, treatment of the disorder.

The interaction between cannabinoids and long-term synaptic plasticity: A survey on memory formation and underlying mechanisms.

Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is an essential phenomenon in memory formation as well as maintenance along with many other cognitive functions, such as those needed for coping with external stimuli. Synaptic plasticity consists of gradual changes in the biochemistry and morphology of pre- and postsynaptic neurons, particularly in the hippocampus. Consuming marijuana as a primary source of exocannabinoids immediately impairs attention and working memory-related tasks. Evidence regarding the effects of cannabinoids on LTP and memory is contradictory. While cannabinoids can affect a variety of specific cannabinoid receptors (CBRs) and nonspecific receptors throughout the body and brain, they exert miscellaneous systemic and local cerebral effects. Given the increasing use of cannabis, mainly among the young population, plus its potential adverse long-term effects on learning and memory processes, it could be a future global health challenge. Indeed, the impact of cannabinoids on memory is multifactorial and depends on the dosage, timing, formula, and route of consumption, plus the background complex interaction of the endocannabinoids system with other cerebral networks. Herein, we review how exogenously administrated organic cannabinoids, CBRs agonists or antagonists, and endocannabinoids can affect LTP and synaptic plasticity through various receptors in interaction with other cerebral pathways and primary neurotransmitters.

Does the Repeated-Bout Effect Influence Post-Activation Performance Enhancement in Recreational Runners?

Purpose: This study examined how a low dose of an eccentric-oriented lunge exercise could induce the repeated-bout effect (RBE) and affect the subsequent post-activation performance enhancement (PAPE) in recreational runners. Methods: Twenty male recreational runners (32.1 ± 2.8 years; 173.4 ± 6.1 cm; 73.3 ± 11.5 kg; 57.8 ± 7.2 mL·kg-1·min-1) were divided into control (N = 10) and experimental (N = 10) groups. In the first and fourth weeks, the groups were assessed for jump capacity, dynamic balance, and submaximal running kinematics before and after an incremental shuttle-run test until exhaustion. The experimental group was also submitted to two sessions of the eccentric-oriented lunge exercise (3 sets of 10 repetitions with 2 min of passive recovery) in the second and third weeks. Results: We observed that the first session promoted muscle damage, which was significantly (p < .05) reduced after the second training session, thus indicating an RBE. Meanwhile, there was no effect of the RBE on dynamic balance and submaximal running kinematics in the post-intervention. However, there was a significant increase in countermovement jump height (p = .008) for the experimental group when compared to the control group, although no PAPE was observed. Conclusions: The current results demonstrate that a simple, low-dose eccentric-oriented exercise may induce an RBE, leading to reduced muscle damage and a possibly improved lower limbs' muscle power in recreational runners. However, the absence of PAPE effects suggests that the RBE may not directly influence the potentiation/fatigue balance after fatiguing running exercises.

Rose Bengal diacetate-mediated antimicrobial photodynamic inactivation: potentiation by potassium iodide and acceleration of wound healing in MRSA-infected diabetic mice.

Previous studies have shown that antimicrobial photodynamic inactivation (aPDI) can be strongly potentiated by the addition of the non-toxic inorganic salt, potassium iodide (KI). This approach was shown to apply to many different photosensitizers, including the xanthene dye Rose Bengal (RB) excited by green light (540 nm). Rose Bengal diacetate (RBDA) is a lipophilic RB derivative that is easily taken up by cells and hydrolyzed to produce an active photosensitizer. Because KI is not taken up by microbial cells, it was of interest to see if aPDI mediated by RBDA could also be potentiated by KI. The addition of 100 mM KI strongly potentiated the killing of Gram-positive methicillin-resistant Staphylocccus aureus, Gram-negative Eschericia coli, and fungal yeast Candida albicans when treated with RBDA (up to 15 µM) for 2 hours followed by green light (540 nm, 10 J/cm2). Both RBDA aPDI regimens (400 µM RBDA with or without 400 mM KI followed by 20 J/cm2 green light) accelerated the healing of MRSA-infected excisional wounds in diabetic mice, without damaging the host tissue.

CPEB2-activated axonal translation of VGLUT2 mRNA promotes glutamatergic transmission and presynaptic plasticity.

BACKGROUND: Local translation at synapses is important for rapidly remodeling the synaptic proteome to sustain long-term plasticity and memory. While the regulatory mechanisms underlying memory-associated local translation have been widely elucidated in the postsynaptic/dendritic region, there is no direct evidence for which RNA-binding protein (RBP) in axons controls target-specific mRNA translation to promote long-term potentiation (LTP) and memory. We previously reported that translation controlled by cytoplasmic polyadenylation element binding protein 2 (CPEB2) is important for postsynaptic plasticity and memory. Here, we investigated whether CPEB2 regulates axonal translation to support presynaptic plasticity. METHODS: Behavioral and electrophysiological assessments were conducted in mice with pan neuron/glia- or glutamatergic neuron-specific knockout of CPEB2. Hippocampal Schaffer collateral (SC)-CA1 and temporoammonic (TA)-CA1 pathways were electro-recorded to monitor synaptic transmission and LTP evoked by 4 trains of high-frequency stimulation. RNA immunoprecipitation, coupled with bioinformatics analysis, were used to unveil CPEB2-binding axonal RNA candidates associated with learning, which were further validated by Western blotting and luciferase reporter assays. Adeno-associated viruses expressing Cre recombinase were stereotaxically delivered to the pre- or post-synaptic region of the TA circuit to ablate Cpeb2 for further electrophysiological investigation. Biochemically isolated synaptosomes and axotomized neurons cultured on a microfluidic platform were applied to measure axonal protein synthesis and FM4-64FX-loaded synaptic vesicles. RESULTS: Electrophysiological analysis of hippocampal CA1 neurons detected abnormal excitability and vesicle release probability in CPEB2-depleted SC and TA afferents, so we cross-compared the CPEB2-immunoprecipitated transcriptome with a learning-induced axonal translatome in the adult cortex to identify axonal targets possibly regulated by CPEB2. We validated that Slc17a6, encoding vesicular glutamate transporter 2 (VGLUT2), is translationally upregulated by CPEB2. Conditional knockout of CPEB2 in VGLUT2-expressing glutamatergic neurons impaired consolidation of hippocampus-dependent memory in mice. Presynaptic-specific ablation of Cpeb2 in VGLUT2-dominated TA afferents was sufficient to attenuate protein synthesis-dependent LTP. Moreover, blocking activity-induced axonal Slc17a6 translation by CPEB2 deficiency or cycloheximide diminished the releasable pool of VGLUT2-containing synaptic vesicles. CONCLUSIONS: We identified 272 CPEB2-binding transcripts with altered axonal translation post-learning and established a causal link between CPEB2-driven axonal synthesis of VGLUT2 and presynaptic translation-dependent LTP. These findings extend our understanding of memory-related translational control mechanisms in the presynaptic compartment.

The duality of amyloid-ß: its role in normal and Alzheimer's disease states.

Alzheimer's disease (AD) is a degenerative neurological condition that gradually impairs cognitive abilities, disrupts memory retention, and impedes daily functioning by impacting the cells of the brain. A key characteristic of AD is the accumulation of amyloid-beta (Aß) plaques, which play pivotal roles in disease progression. These plaques initiate a cascade of events including neuroinflammation, synaptic dysfunction, tau pathology, oxidative stress, impaired protein clearance, mitochondrial dysfunction, and disrupted calcium homeostasis. Aß accumulation is also closely associated with other hallmark features of AD, underscoring its significance. Aß is generated through cleavage of the amyloid precursor protein (APP) and plays a dual role depending on its processing pathway. The non-amyloidogenic pathway reduces Aß production and has neuroprotective and anti-inflammatory effects, whereas the amyloidogenic pathway leads to the production of Aß peptides, including Aß40 and Aß42, which contribute to neurodegeneration and toxic effects in AD. Understanding the multifaceted role of Aß, particularly in AD, is crucial for developing effective therapeutic strategies that target Aß metabolism, aggregation, and clearance with the aim of mitigating the detrimental consequences of the disease. This review aims to explore the mechanisms and functions of Aß under normal and abnormal conditions, particularly in AD, by examining both its beneficial and detrimental effects.

The effects of blood flow restriction training on post activation potentiation and upper limb muscle activation: a meta-analysis.

Objective: This meta-analysis aims to systematically evaluate the impact of blood flow restriction training (BFRT) on muscle activation and post-activation potentiation (PAP) in the upper limbs, to provide guidance for upper limb protocols aiming to enhance explosive strength and activation. Methods: PubMed, CNKI, Web of Science, and EBSCO databases were queried to identify randomized controlled trials (RCTs) investigating the effects of upper limb BFRT on muscle activation and PAP. Inclusion and exclusion criteria were applied using the Cochrane bias risk tool. Literature quality assessment and statistical analysis were conducted using Revman 5.4 and Stata 17.0 software. Sensitivity analysis and funnel plots were utilized to assess result stability and publication bias. Results: A total of 31 articles involving 484 participants were included in the analysis. Meta-analysis results showed that upper limb BFRT significantly increased muscle iEMG values [SMD = 0.89, 95%CI (0.21, 1.58), p = 0.01]. BFRT had a significant effect on upper limb explosive force [SMD = 0.73, 95%CI (0.41, 1.04), p < 0.00001]. Subgroup analysis based on literature heterogeneity (I 2 = 92%, 80%) showed that exhaustive BFRT significantly decreased upper limb iEMG [SMD = -0.67, 95%CI (-1.25, -0.09), p = 0.01], with exercise modes including maximum output power of bench press [SMD = 1.87, 95%CI (0.22, 3.53), p < 0.0001], exercise intensity of 40%-70% 1RM [SMD = 1.31, 95%CI (0.61, 2.01), p < 0.0001], and pressure intensity of ≥60% AOP [SMD = 0.83, 95%CI (0.43, 1.23), p < 0.0001] reaching maximum effects and statistical significance. Conclusion: Upper limb BFRT can induce muscle activation and PAP. BFRT with 40%-70% 1RM and ≥60% AOP in the upper limbs is more likely to promote PAP. Systematic Review Registration: http://inplasy.com, identifier INPLASY202430008.

A Microtiter Plate Assay at Acidic pH to Identify Potentiators that Enhance Pyrazinamide Activity Against Mycobacterium tuberculosis.

Pyrazinamide (PZA) is a key component of chemotherapy for the treatment of drug-susceptible tuberculosis (TB) and is likely to continue to be included in new drug combinations. Potentiation of PZA could be used to reduce the emergence of resistance, shorten treatment times, and lead to a reduction in the quantity of PZA consumed by patients, thereby reducing the toxic effects. Acidified medium is required for the activity of PZA against Mycobacterium tuberculosis. In vitro assessments of pyrazinamide activity are often avoided because of the lack of standardization, which has led to a lack of effective in vitro tools for assessing and/or enhancing PZA activity.We have developed and optimized a novel, robust, and reproducible, microtiter plate assay, that centers around acidity levels that are low enough for PZA activity. The assay can be applied to the evaluation of novel compounds for the identification of potentiators that enhance PZA activity. In this assay, potentiation of PZA is demonstrated to be statistically significant with the addition of rifampicin (RIF), which can, therefore, be used as a positive control. Conversely, norfloxacin demonstrates no potentiating activity with PZA and can be used as a negative control. The method, and the associated considerations, described here, can be adapted in the search for potentiators of other antimicrobials.

Phase 1 study of the pharmacokinetics and clinical proof-of-concept activity of a biofilm-disrupting human monoclonal antibody in patients with chronic prosthetic joint infection of the knee or hip.

We report the results of a first-in-human phase 1 clinical study to evaluate TRL1068, a native human monoclonal antibody that disrupts bacterial biofilms with broad-spectrum activity against both Gram-positive and Gram-negative species. The study population consisted of patients with chronic periprosthetic joint infections (PJIs) of the knee or hip, including both monomicrobial and polymicrobial infections, that are highly resistant to antibiotics due to biofilm formation. TRL1068 was administered via a single pre-surgical intravenous infusion in three sequentially ascending dose groups (6, 15, and 30 mg/kg). Concomitant perioperative antibiotics were pathogen-targeted as prescribed by the treating physician. In this double-blinded study, 4 patients were randomized to receive placebo and 11 patients to receive TRL1068 on day 1, as well as targeted antibiotics for 7 days prior to the scheduled removal of the infected implant and placement of an antibiotic-eluting spacer as the first stage of the standard of care two-stage exchange arthroplasty. No adverse events attributable to TRL1068 were reported. TRL1068 serum half-life was 15-18 days. At day 8, the concentration in synovial fluid was approximately 60% of the blood level and thus at least 15-fold above the threshold for biofilm-disrupting activity in vitro. Explanted prostheses were sonicated to release adherent bacteria for culture, with elimination of the implant bacteria observed in 3 of the 11 patients who received TRL1068, which compares favorably to prior PJI treatments. None of the patients who received TRL1068 had a relapse of the original infection by the end of the study (day 169). CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04763759.

A distinct foliar pigmentation pattern formed by activator-repressor gradients upstream of an anthocyanin-activating R2R3-MYB.

The emergence of novel traits is often preceded by a potentiation phase, when all the genetic components necessary for producing the trait are assembled. However, elucidating these potentiating factors is challenging. We have previously shown that an anthocyanin-activating R2R3-MYB, STRIPY, triggers the emergence of a distinct foliar pigmentation pattern in the monkeyflower Mimulus verbenaceus. Here, using forward and reverse genetics approaches, we identify three potentiating factors that pattern STRIPY expression: MvHY5, a master regulator of light signaling that activates STRIPY and is expressed throughout the leaf, and two leaf developmental regulators, MvALOG1 and MvTCP5, that are expressed in opposing gradients along the leaf proximodistal axis and negatively regulate STRIPY. These results provide strong empirical evidence that phenotypic novelties can be potentiated through incorporation into preexisting genetic regulatory networks and highlight the importance of positional information in patterning the novel foliar stripe.

The impact of post-activation potentiation on explosive vertical jump after intermittent time: a meta-analysis and systematic review.

The optimal intermittent time for post-activation potentiation (PAP) training remains uncertain and contentious. This study employed a meta-analysis to systematically evaluate the effect of different intermittent times on PAP in relation to explosive vertical jump height. Relevant literature was sourced from CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, and Google Scholar databases using keywords such as "postactivation potentiation," "activation enhancement effect," "PAP," "explosive vertical jump," "explosive vertical high jump," and "intermittent time." The search covered publications from the inception of each database until June 2024. Studies involving athletes (regardless of sport type) undergoing PAP training were included, with no restrictions on the methods used to induce PAP. Comparative analysis focused on the heights of countermovement jumps (CMJ) and peak ground reaction force (GRF) before and after interventions. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool, and data were analyzed using RevMan5.3. The study included a total of 21 papers with 327 subjects, primarily using the squat as the method of PAP induction. The meta-analysis revealed that intermittent times of 4 min [MD = - 0.03, 95% CI: - 0.04 ~ - 0.01; Z = 2.71, P = 0.007] and 5-8 min [MD = - 0.03, 95% CI: - 0.04 ~ - 0.01; Z = 3.07, P = 0.002] significantly increased the height of explosive vertical CMJs. However, intermittent times of 1-3 min [MD = -0.00, 95% CI: - 0.01 ~ 0.01; Z = 0.38, P = 0.70] and 10-24 min [MD = - 0.01, 95% CI: - 0.02 ~ 0.00; Z = 1.43, P = 0.15] did not show significant effects on CMJ height. These findings indicate that 4-min and 5-8 min intervals significantly enhance CMJ height, while intervals shorter than 4 min or longer than 8 min do not have a significant impact.

Maternal linalool treatment protects against radiofrequency wave-induced deteriorations in adolescent rats: A behavioral and electrophysiological study.

Recent years, the rapid advancement of technology has raised concerns. We studied the effects of prenatal exposure to 900 MHz radiofrequency (RF) from mobile phones and the protective effects of linalool on learning and memory, and anxiety in adolescent male and female offspring rats. Pregnant rats were divided into four groups: control, wave, wave + linalool, and linalool. Rats received linalool (25mg/kg) by gavage for 21 days. Irradiation was conducted from day 0 to day 21 of pregnancy. Offsprings underwent behavioral and electrophysiological tests on days 50 and 60 after birth. Exposure to RF during pregnancy caused anxiety-like behavior in the EPM test and impairment of learning and memory in the Morris water maze and shuttle box tests. Electrophysiological properties and synaptic plasticity of the dorsal hippocampal CA3-CA1 synapse showed a decrease in fEPSP amplitude and slope. The trace element levels in both male and female offspring were consistent across all groups compared to their respective controls. In the hippocampus tissue, the levels of Fe, Cu, and Mn, as well as the Cu/Zn ratio, were significantly higher in the exposed groups (wave groups) compared to their controls. Moreover, Zn levels were significantly lower in the hippocampus tissue of the exposed groups. Linalool administration mitigated the excessive increase in Fe, Cu, Mn, and Cu/Zn ratio and normalized the disrupted levels of trace elements, except for Zn levels in both male and female offspring. Sex differences were observed in the EPM and shuttle box tests, females were more sensitive than males. In summary, our study demonstrates that prenatal exposure to mobile phone radiation induces stress-like behaviors, disrupts learning and memory, alters hippocampal electrophysiological properties and trace element balance in offspring. Treatment with linalool mitigates these deleterious effects, highlighting its potential as a therapeutic intervention. These findings contribute to our understanding of the impact of prenatal environmental exposures on neurodevelopment and offer insights into potential strategies for neuroprotection.

Pretreatment of Melanoma Cells with Aqueous Ethanol Extract from Madhuca longifolia Bark Strongly Potentiates the Activity of a Low Dose of Dacarbazine.

Madhuca longifolia is an evergreen tree distributed in India, Nepal, and Sri Lanka. This tree is commonly known as Mahua and is used in traditional medicine. It was demonstrated that ethanol extract from the bark of M. longifolia possessed potent cytotoxic activity towards two melanoma cell lines, in contrast to aqueous extract that exhibited no activity. Apart from being selectively cytotoxic to cancer cells (with no activity towards non-cancerous fibroblasts), the studied extract induced apoptosis and increased reactive oxygen species generation in melanoma cells. Additionally, the use of the extract together with dacarbazine (both in non-toxic concentrations) resulted in the enhancement of their anticancer activity. Moreover, the pretreatment of melanoma cells with M. longifolia extract potentiated the activity of a low dose of dacarbazine to an even higher extent. It was concluded that ethanol extract of M. longifolia sensitized human melanoma cells to chemotherapeutic drugs. It can therefore be interesting as a promising source of compounds for prospective combination therapy.

Exploring the Effect of Arsenic-Containing Hydrocarbon on the Bidirectional Synaptic Plasticity of the Dorsal Hippocampus.

Arsenic-containing hydrocarbons (AsHCs) are common in marine organisms. However, there is little research on their effects on the central nervous system's advanced activities, such as cognition. Bidirectional synaptic plasticity dynamically regulates cognition through the balance of long-term potentiation (LTP) and long-term depression (LTD). However, the effects of AsHCs on bidirectional synaptic plasticity and the underlying molecular mechanisms remain unexplored. This study provides the first evidence that 15 µg As L-1 AsHC 360 enhances bidirectional synaptic plasticity, occurring during the maintenance phase rather than the baseline phase. Further calcium gradient experiments hypothesize that AsHC 360 may enhance bidirectional synaptic plasticity by affecting calcium ion levels. The enhancement of bidirectional synaptic plasticity by 15 µg As L-1 AsHC 360 holds significant implications in improving cognitive function, treating neuro-psychiatric disorders, promoting neural recovery, and enhancing brain adaptability.

Association of connexin36 with adherens junctions at mixed synapses and distinguishing electrophysiological features of those at mossy fiber terminals in rat ventral hippocampus.

BACKGROUND: Granule cells in the hippocampus project axons to hippocampal CA3 pyramidal cells where they form large mossy fiber terminals. We have reported that these terminals contain the gap junction protein connexin36 (Cx36) specifically in the stratum lucidum of rat ventral hippocampus, thus creating morphologically mixed synapses that have the potential for dual chemical/electrical transmission. METHODOLOGY: Here, we used various approaches to characterize molecular and electrophysiological relationships between the Cx36-containing gap junctions at mossy fiber terminals and their postsynaptic elements and to examine molecular relationships at mixed synapses in the brainstem. RESULTS: In rat and human ventral hippocampus, many of these terminals, identified by their selective expression of vesicular zinc transporter-3 (ZnT3), displayed multiple, immunofluorescent Cx36-puncta representing gap junctions, which were absent at mossy fiber terminals in the dorsal hippocampus. In rat, these were found in close proximity to the protein constituents of adherens junctions (i.e., N-cadherin and nectin-1) that are structural hallmarks of mossy fiber terminals, linking these terminals to the dendritic shafts of CA3 pyramidal cells, thus indicating the loci of gap junctions at these contacts. Cx36-puncta were also associated with adherens junctions at mixed synapses in the brainstem, supporting emerging views of the structural organization of the adherens junction-neuronal gap junction complex. Electrophysiologically induced long-term potentiation (LTP) of field responses evoked by mossy fiber stimulation was greater in the ventral than dorsal hippocampus. CONCLUSIONS: The electrical component of transmission at mossy fiber terminals may contribute to enhanced LTP responses in the ventral hippocampus.

Are Surface Electromyography Parameters Indicative of Post-Activation Potentiation/Post-Activation Performance Enhancement, in Terms of Twitch Potentiation and Voluntary Performance? A Systematic Review.

The aim was to identify if surface electromyography (sEMG) parameters are indicative of post-activation potentiation (PAP)/post-activation performance enhancement (PAPE), in terms of twitch potentiation and voluntary performance. Three databases were used in April 2024, with the following inclusion criteria: (a) original research, assessed in healthy human adults, and (b) sEMG parameters were measured. The exclusion criteria were (a) studies with no PAP/PAPE protocol and (b) non-randomized control trials. The following data were extracted: study characteristics/demographics, PAP/PAPE protocols, sEMG parameters, twitch/performance outcomes, and study findings. A modified physiotherapy evidence database (PEDro) scale was used for quality assessment. Fifteen randomized controlled trials (RCTs), with a total of 199 subjects, were included. The M-wave amplitude (combined with a twitch torque outcome) was shown to generally be indicative of PAP. The sEMG amplitudes (in some muscles) were found to be indicative of PAPE during ballistic movements, while a small decrease in the MdF (in certain muscles) was shown to reflect PAPE. Changes in the Hmax/Mmax ratio were found to contribute (temporally) to PAP, while the H-reflex amplitude was shown to be neither indicative of PAP nor PAPE. This review provides preliminary findings suggesting that certain sEMG parameters could be indicative of PAP/PAPE. However, due to limited studies, future research is warranted.

Optimizing GABAA receptor antagonism for the induction of long-term potentiation in the mouse and rat dentate gyrus in vitro.

The reliable induction of long-term potentiation (LTP) in the dentate gyrus (DG) in vitro requires the blockade of the γ-aminobutyric acid A (GABAA) receptor. In these studies we examined the effectiveness of the specific GABAA receptor antagonist bicuculline methiodide (BMI) in facilitating LTP in the DG from hippocampal slices obtained from either C57Bl/6 mice or Sprague-Dawley rats, two species commonly used for electrophysiology. In the C57Bl/6 mice, maximal short-term potentiation and LTP in the DG were produced with a concentration of 5 µM BMI. In contrast, a concentration of 10 µM BMI was required to produce maximal short-term potentiation and LTP in the DG of Sprague-Dawley rats. These results reveal that there are species differences in the optimal amount of BMI required to produce robust and reliable LTP in the rodent DG in vitro and highlight the need to take consideration of the species being used when choosing concentrations of pharmacological agents to employ for electrophysiological use.NEW & NOTEWORTHY In this report we provide specific neurophysiological evidence for concentrations of GABAA antagonist required to study long-term potentiation in the medial perforant pathway of the dentate gyrus. Two commonly used species, Sprague-Dawley rats and C57Bl/6 mice, require different concentrations of bicuculline methiodide to induce optimal short-term and long-term potentiation.