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Regular physical exercise enhances memory functions, synaptic plasticity in the hippocampus, and brain derived neurotrophic factor (BDNF) levels. Likewise, short periods of exercise, or acute exercise, benefit hippocampal plasticity in rodents, via increased endocannabinoids (especially anandamide, AEA) and BDNF release. Yet, it remains unknown whether acute exercise has similar effects on BDNF and AEA levels in humans, with parallel influences on memory performance. Here we combined blood biomarkers, behavioral, and fMRI measurements to assess the impact of a single session of physical exercise on associative memory and underlying neurophysiological mechanisms in healthy male volunteers. For each participant, memory was tested after three conditions: rest, moderate or high intensity exercise. A long-term memory retest took place 3 months later. At both test and retest, memory performance after moderate intensity exercise was increased compared to rest. Memory after moderate intensity exercise correlated with exercise-induced increases in both AEA and BNDF levels: while AEA was associated with hippocampal activity during memory recall, BDNF enhanced hippocampal memory representations and long-term performance. These findings demonstrate that acute moderate intensity exercise benefits consolidation of hippocampal memory representations, and that endocannabinoids and BNDF signaling may contribute to the synergic modulation of underlying neural plasticity mechanisms.

Therapeutic cannabis administration is increasingly used in Western countries due to its positive role in several pathologies. Dronabinol or tetrahydrocannabinol (THC) pills, ethanolic cannabis tinctures, oromucosal sprays or table vaporizing devices are available but other cannabinoids forms can be used. Inspired by the illegal practice of dabbing of butane hashish oil (BHO), cannabinoids from cannabis were extracted with butane gas and the resulting concentrate (BHO) was atomized with specific vaporizing devices. The efficiency of “cannavaping,” defined as the “vaping” of liquid refills for e-cigarettes enriched with cannabinoids, including BHO, was studied as an alternative route of administration for therapeutic cannabinoids. The results showed that illegal cannavaping would be subjected to marginal development due to the poor solubility of BHO in commercial liquid refills (especially those with high glycerin content). This prevents the manufacture of liquid refills with high BHO concentrations adopted by most recreational users of cannabis to feel the psychoactive effects more rapidly and extensively. Conversely, “therapeutic cannavaping” could be an efficient route for cannabinoids administration because less concentrated cannabinoids-enriched liquid refills are required. However, the electronic device marketed for therapeutic cannavaping should be carefully designed to minimize potential overheating and contaminant generation.

Acute physical exercise improves memory functions by increasing neural plasticity in the hippocampus. In animals, a single session of physical exercise has been shown to boost anandamide (AEA), an endocannabinoid known to promote hippocampal plasticity. Hippocampal neuronal networks encode episodic memory representations, including the temporal organization of elements, and can thus benefit motor sequence learning. While previous work established that acute physical exercise has positive effects on declarative memory linked to hippocampal plasticity mechanisms, its influence on memory for motor sequences, and especially on neural mechanisms underlying possible effects, has been less investigated. Here we studied the impact of acute physical exercise on motor sequence learning, and its underlying neurophysiological mechanisms in humans, using a cross-over randomized within-subjects design. We measured behavior, fMRI activity, and circulating AEA levels in fifteen healthy participants while they performed a serial reaction time task before and after a short period of exercise (moderate or high intensity) or rest. We show that exercise enhanced motor sequence memory, significantly for high intensity exercise and tending towards significance for moderate intensity exercise. This enhancement correlated with AEA increase, and dovetailed with local increases in caudate nucleus and hippocampus activity. These findings demonstrate that acute physical exercise promotes sequence learning, thus attesting the overarching benefit of exercise to hippocampus-related memory functions.

Simultaneous assessment of a panel of protein markers is becoming essential in order to enhance biomarker research and improve diagnostics. Specifically, postmortem diagnostics of early myocardial ischemia in sudden cardiac death cases could benefit from a multiplex marker assessment in the same tissue section. Current analytical antibody-based techniques (immunohistochemistry and immunofluorescence) limit multiplex analysis usually to not more than three antibodies. In this study, mass spectrometry-immunohistochemistry (MS-IHC) was performed by combining laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) with rare-metal-isotope-tagged antibodies as a technique for multiplex analysis of human postmortem myocardial tissue samples. Tissue sections with myocardial infarction were simultaneously analyzed for seven primary, rare-metal-isotope-tagged antibodies (troponin T, myoglobin, fibronectin, C5b-9, unphosphorylated connexin 43, VEGF-B, and JunB). Comparison between the MS-IHC approach and chromogenic IHC showed similar patterns in ionic and optical images. In addition, absolute quantification was performed by MS-IHC, providing a proportional relationship between the signal intensity and the local marker concentration in tissue sections. These data demonstrated that LA-ICP-MS combined with rare-metal-isotope-tagged antibodies is an efficient strategy for simultaneous testing of multiple markers and allows not only visualization of molecules within the tissue but also quantification of the signal. Such imaging approach has a great potential in both diagnostics and pathology-related research.

A cross-over controlled administration study of smoked cannabis was carried out on occasional and heavy smokers. The participants smoked a joint (11 % Δ9-tetrahydrocannabinol (THC)) or a matching placebo on two different occasions. Whole blood (WB) and oral fluid (OF) samples were collected before and up to 3.5 h after smoking the joints. Pharmacokinetic analyses were obtained from these data. Questionnaires assessing the subjective effects were administered to the subjects during each session before and after the smoking time period. THC, 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THCCOOH) were analyzed in the blood by gas chromatography or liquid chromatography (LC)-tandem mass spectrometry (MS/MS). The determination of THC, THCCOOH, cannabinol (CBN), and Δ9-tetrahydrocannabinolic acid A (THC-A) was carried out on OF only using LC-MS/MS. In line with the widely accepted assumption that cannabis smoking results in a strong contamination of the oral cavity, we found that THC, and also THC-A, shows a sharp, high concentration peak just after smoking, with a rapid decrease in these levels within 3 h. No obvious differences were found between both groups concerning THC median maximum concentrations measured either in blood or in OF; these levels were equal to 1,338 and 1,041 μg/L in OF and to 82 and 94 μg/L in WB for occasional and heavy smokers, respectively. The initial WB THCCOOH concentration was much higher in regular smokers than in occasional users. Compared with the occasional smokers, the sensation of confusion felt by the regular smokers was much less while the feeling of intoxication remained almost unchanged. Figure Time profiles of THC, 11-OH-THC, and THCCOOH in whole blood for occasional (a) and heavy cannabis smokers (b)

The objective of this work was to combine the advantages of the dried blood spot (DBS) sampling process with the highly sensitive and selective negative-ion chemical ionization tandem mass spectrometry (NICI-MS-MS) to analyze for recent antidepressants including fluoxetine, norfluoxetine, reboxetine, and paroxetine from micro whole blood samples (i.e., 10 μL). Before analysis, DBS samples were punched out, and antidepressants were simultaneously extracted and derivatized in a single step by use of pentafluoropropionic acid anhydride and 0.02% triethylamine in butyl chloride for 30 min at 60 °C under ultrasonication. Derivatives were then separated on a gas chromatograph coupled with a triple-quadrupole mass spectrometer operating in negative selected reaction monitoring mode for a total run time of 5 min. To establish the validity of the method, trueness, precision, and selectivity were determined on the basis of the guidelines of the “Société Française des Sciences et des Techniques Pharmaceutiques” (SFSTP). The assay was found to be linear in the concentration ranges 1 to 500 ng mL⁻¹ for fluoxetine and norfluoxetine and 20 to 500 ng mL⁻¹ for reboxetine and paroxetine. Despite the small sampling volume, the limit of detection was estimated at 20 pg mL⁻¹ for all the analytes. The stability of DBS was also evaluated at −20 °C, 4 °C, 25 °C, and 40 °C for up to 30 days. Furthermore, the method was successfully applied to a pharmacokinetic investigation performed on a healthy volunteer after oral administration of a single 40-mg dose of fluoxetine. Thus, this validated DBS method combines an extractive—derivative single step with a fast and sensitive GC-NICI-MS-MS technique. Using microliter blood samples, this procedure offers a patient-friendly tool in many biomedical fields such as checking treatment adherence, therapeutic drug monitoring, toxicological analyses, or pharmacokinetic studies.

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was performed to map elements in thin formalin-fixed paraffin-embedded tissue sections of two forensic cases with firearm and electrocution injuries, respectively. In both cases, histological examination of the wounded tissue regions revealed the presence of exogenous aggregates that may be interpreted as metallic depositions. The use of imaging LA-ICP-MS allowed us to unambiguously determine the elemental composition of the observed aggregates assisting the pathologist in case assessments. To the best of our knowledge, we demonstrate for the first time the use of imaging LA-ICP-MS as a complementary tool for forensic pathologists and toxicologists in order to map the presence of metals and other elements in thin tissue sections of post-mortem cases.

Habitat selection is a key mechanism that enables animals to optimize their fitness in response to varying environmental conditions. Differences in habitat selection between geographical areas may imply behavioral adaptations to local environmental conditions. Understanding the potential of adaptation of species along broad geographical ranges is of primary interest to anticipate potential changes in species behavior or distribution range in the context of climate changes. In this study, we investigated the habitat selection and the daily movement patterns of the Eurasian Woodcock, Scolopax rusticola, a bird species that winters across widely varying climatic zones. We tracked 89 individuals wintering in the Mediterranean regions with GPS-VHF transmitters, where climate and habitats conditions differ significantly from the oceanic regions. To assess how they responded to varying habitat and environmental conditions, we collected data across four geographical regions spanning a gradient of Mediterranean climatic influence — ranging from northern subareas with denser forest and deeper soil to southern subareas characterized by less productive forests, garrigues, and rocky soil. In wetter regions, woodcocks generally commuted between diurnal resting in forested areas and nocturnal feeding in open habitats, though less frequently than described in studies from other climatic regions. Under drier conditions, they often remained within forest habitats, displaying higher daytime activity and reduced nocturnal movement. Across all subareas, denser forests were selected during the day. The selection for nocturnal forest microhabitats varied by subarea, e.g., denser low vegetation was more strongly selected in southern subareas, while forest habitats highly covered by forest herbs were mostly avoided in northern subareas. Our findings underscore the remarkable behavioral flexibility of woodcocks, highlighting their potential to adapt to global change. However, the occurrence of escape movements under the driest conditions suggest that this change in behavior and habitat selection may be an early warning sign of the effects of climate change on the wintering areas. Overall, our study emphasizes the need to study the ecology of species across diverse environmental conditions to better understand their habitat requirements and adaptive capacity.

Recent studies suggest that acute physical exercise improves memory functions by increasing neural plasticity in the hippocampus. In animals, a single session of physical exercise has been shown to boost AEA (anandamide), an endocannabinoid known to promote hippocampal plasticity, which may in turn benefit hippocampal-dependent learning. Hippocampal neuronal networks do not only encode episodic memory representations, but also contribute to the sequential organization of memory elements, including motor sequences (Schendan et al., 2003; Eichenbaum, 2017). While previous work established that acute physical exercise has positive effects on declarative memory, whether it also influences memory for motor sequences remains unresolved. Here we studied the impact of moderate and high intensity acute physical exercise on motor sequence learning, and its underlying neurophysiological mechanisms in humans. To this end, we acquired behavioral, fMRI and AEA level data in fifteen healthy participants across three visits while they performed a serial reaction time task (SRTT) before and after a period of exercise (moderate or high intensity) or rest. We report that physical exercise increased AEA levels, and activity in the right hippocampus and caudate nucleus. Activity in both areas was directly linked to SRTT performance, which itself correlated with circulating AEA levels. These findings support that acute physical exercise favors hippocampal plasticity and potentially its broader role in memory function, including the consolidation of motor sequences.

It is well established that regular physical exercise enhances memory functions, synaptic plasticity in the hippocampus, and BDNF (Brain Derived Neurotrophic Factor) levels. Likewise, acute exercise benefits hippocampal plasticity in rodents, via increased endocannabinoids (especially anandamide, AEA) and BDNF release. Yet, whether acute exercise affects BDNF and AEA levels and influences memory performance in humans, remains to date unknown. Here we combined blood biomarkers, behavioral, and fMRI measurements to assess the impact of acute physical exercise on associative memory and underlying neurophysiological mechanisms. For each participant, memory was tested after three conditions: rest, moderate or high intensity exercise. A long-term memory retest took place 3 months later. At both test and retest, memory performance after moderate intensity exercise was increased compared to rest and high intensity exercise. We also show that memory after moderate intensity exercise benefited from exercise-induced increases in both AEA and BNDF levels: while AEA boosted hippocampal activity during memory recall, BDNF enhanced hippocampal memory representations and long-term performance. These findings confirm previous results on the benefits of acute exercise towards memory consolidation and, by including the contribution of key biomarkers, extend them by explaining neural plasticity mechanisms mediating cognitive enhancement.