The Sobering Sting: Oleoyl Serotonin Is a Novel Stephanoconus Snail Venom-Derived Antagonist of Cannabinoid Receptors That Counteracts Learning and Memory Deficits.

Cannabinoid receptors (CB1 and CB2) are promising targets for a better understanding of neurological diseases. Nevertheless, only a few ligands of CB have reached clinical application so far. Venoms are considered as interesting sources of novel biologically active compounds. Here, we describe an endocannabinoid-like molecule, oleoyl serotonin (OS), present in the venom of Stephanoconus snails. Using electrophysiological assays, it was shown that OS inhibits CB1 and CB2. Structure-activity relationship studies using a chimeric CB1/2 revealed that the domain encompassing the transmembrane helix V (TMHV)- intracellular loop 3 (ICL3)-TMHVI of the CB2 is critical for the binding and function of OS. We concluded that OS binds to sites of the CB2 that are different from the binding sites of the non-selective CB agonist WIN55,212-2. Behavioral assays in mice showed that OS counteracted learning and memory deficits caused by WIN55,212-2. Furthermore, a selectivity screening of OS showed high selectivity for CB over various ion channels and receptors. Overall, OS may represent a new approach to the prevention and treatment of learning and memory cognition impairment in neurological diseases.

Supplementation with Manihot esculenta Crantz (Cassava) leaves' extract prevents recognition memory deficits and hippocampal antioxidant dysfunction induced by Amyloid-ß.

OBJECTIVE: The Manihot esculenta Crantz (Cassava) is a typical South American plant rich in nutrients and energetic compounds. Lately, our group has shown that non-pharmacological interventions with natural antioxidants present different neuroprotective effects on oxidative balance and memory deficits in AD-like animal models. Here, our objective was to evaluate the neuroprotective effects of Cassava leaves' extract (CAS) in an AD-like model induced by amyloid-beta (Aß) 25-35 peptide. METHODS: Male Wistar rats (n = 40; 60 days old) were subjected to 10 days of CAS supplementation; then, we injected 2 µL Aß 25-35 in the hippocampus by stereotaxic surgery. Ten days later, we evaluated object recognition (OR) memory. Cassavas' total polyphenols, flavonoids, and condensed tannins content were measured, as well as hippocampal lipid peroxidation and total antioxidant capacity. RESULTS: CAS protected against Aß-induced OR memory deficits. In addition, Aß promoted antioxidant capacity decrease, while CAS was able to prevent it, in addition to diminishing lipoperoxidation compared to Aß. DISCUSSION: We show that treatment with Cassava leaves' extract before AD induction prevents recognition memory deficits related to Aß hippocampal injection. At least part of these effects can be related to the Cassava leaves' extract supplementation effects on diminishing lipid peroxidation and preventing a decrease in the hippocampal total antioxidant capacity in the hippocampus of AD-like animals without adverse effects. Once cassavais a plant of warm and dry ground that can adapt to growon various soil types and seems to resist several insects, our results enable Cassava to be considered asa potential preventive intervention to avoid or minimizeAD-induced memory deficits worldwide.

Acute physical exercise improves recognition memory via locus coeruleus activation but not via ventral tegmental area activation.

Both animals and humans have been studied to explore the impact of acute physical exercise (PE) on memory. In rats, a single session of PE enhances the persistence of novel object recognition (NOR) memory, which depends on dopamine and noradrenaline activity in the hippocampus. However, limited research has examined the involvement of other brain regions in this phenomenon. In this study, we investigated the role of the ventral tegmental area (VTA) and locus coeruleus (LC) in modulating the persistence of NOR memory induced by acute PE. After NOR training, some animals underwent a 30 min treadmill PE session, followed by infusion of either vehicle (VEH) or muscimol (MUS) in either the VTA or LC. Other animals did not undergo PE and only received VEH, MUS, or NMDA within the same time window. We evaluated memory recall 1, 7, and 14 days later. Acute PE promoted memory persistence for up to 14 days afterward, similar to NMDA glutamatergic stimulation of the VTA or LC. Moreover, only the LC region was required for the memory improvement induced by acute PE since blocking this region with MUS impaired NOR encoding. Our findings suggest that acute PE can improve learning within a closed time window, and this effect depends on LC, but not VTA, activity.

Starting maternal exercise, unlike reducing the intensity of exercise during pregnancy, prevents memory deficits in female offspring subject to maternal deprivation.

Maternal deprivation (MD) leads to long-lasting memory deficits. Conversely, maternal exercise could potently modify the offspring's cellular machinery. Here, we tested whether starting to run or reducing the intensity of running during pregnancy can protect prepubertal female offspring against MD-induced memory deficits. Female rats were divided into different groups submitted or not to MD: one started to run before pregnancy and reduced the intensity during the pregnancy (PGE); another started to run at the beginning of pregnancy (GE); and, finally, a control group (CT) was not submitted to exercise. All the rats but those of the CT ran on a treadmill until the delivery day (PND 0). Subsequently, MD was performed from PND 1 to 10. We assessed object recognition (OR) and spatial memory (SM) of female offspring after weaning (PND22, pre-pubertal stage). MD caused OR memory deficit; GE female offspring did not present this deficit, but PGE did. Both PGE and GE alone enhanced offspring spatial learning, but their combination with MD impaired it. MD promoted hippocampal lipid peroxidation increase, which both PGE and GE prevented. Total antioxidant capacity in the hippocampus was higher in both MD-exercised groups compared to all others. Although the antioxidant effects of exercise were similar in both MD exercise groups, we observed better results in the memory tests in the GE group than in the PGE group. These results suggest that starting to exercise during pregnancy is better than reducing the exercise intensity during pregnancy to prevent MD-induced memory deficits in female offspring.

A 3-D-printed synaptic puzzle contributes to students' synaptic transmission comprehension.

We created the "3-dimensional synaptic puzzle" (3Dsp) as an educational resource for the physiology teaching of synaptic transmission (ST). In this study, we aimed to apply and evaluate the use of 3Dsp. For this, we divided 175 university students from public and private universities into two groups: 1) control (CT; students that were only exposed to traditional class or video lessons about ST), and; 2) test (3Dsp; students that were exposed to the 3Dsp practical class in addition to the traditional theoretical class). ST knowledge of students was evaluated before, immediately after, and 15 days after interventions. Additionally, students completed a questionnaire about their perception of teaching-learning methods used in physiology classes and their self-perception of engagement in the physiology content. The CT groups improved their ST knowledge score from pretest to immediate (P < 0.0001 for all groups) and late posttest (P < 0.0001 for all groups). 3Dsp groups also enhanced their score from pretest to immediate (P = 0.029 for public university students; P < 0.0001 for private university students) and late posttest (P < 0.0001 for all groups). We also observed improvement from the immediate to late posttest in the 3Dsp group from private universities (P < 0.001). Both private groups performed better in general ST and specific electrical synapse questions in the pretest and immediate posttest compared to the public CT group (P < 0.05 for all comparisons). More than 90% of the students from both universities affirmed that the 3Dsp contributed to their physiology comprehension and that they would recommend the use of the 3-D models to other teachers in their classes.NEW & NOTEWORTHY We included a 3-dimensional puzzle (3Dsp) of electrical and chemical synapses in the physiology of synaptic transmission (ST) teaching. After a traditional or video lesson class, students from private and public universities were oriented to use the educational resource. More than 90% of the students affirmed that the 3Dsp improved their comprehension of ST content.

Neuroprotective effects of strength training in a neuroinflammatory animal model.

BACKGROUND: The preventive role of muscular strength on diminishing neuroinflammation is yet unknown. In this study, the role of the prophylactic muscular strength exercise was investigated in order to verify whether it would diminish cognitive alterations and modify the antioxidant intracellular scenery in an animal neuroinflammatory model in of the CA1 region of the hippocampus. METHODS: The animals received muscular strength training (SE) three times a week for eight weeks. Subsequently, the stereotaxic surgery was performed with an intra-hippocampal infusion of either saline solution (SAL) or lipopolysaccharide (LPS). Next, we performed the behavioral tests: object recognition and social recognition. Then, the animals were euthanized, and their hippocampus and prefrontal cortex were collected. In another moment, we performed the dosage of the antioxidant activity and histological analysis. RESULTS: The results showed that the muscular strength exercises could show a beneficial prophylactic effect in the cognitive deficiencies caused by acute neuroinflammation. Regarding oxidative stress, there was an increase in catalase enzyme activity (CAT) in the group (SE + LPS) compared to the control groups (p < 0.05). As for the cognitive alterations, there were found in the (SE + LPS) group, diminishing the mnemonic hazard of the discriminative and social memories compared to the control groups (p < 0.05). CONCLUSION: We concluded, therefore, that the exercise performed prophylactically presents a protective effect capable of minimizing such mnemonic deficits and increasing catalase enzyme activity in rats that suffered a local neuroinflammatory process in the hippocampus.

Report on the online course "Basic Concepts in Neurophysiology": a course promoted during the COVID-19 pandemic quarantine.

"Basic Concepts in Neurophysiology" was a 3-wk online course developed during six synchronous meetings combined with asynchronous activities. We proposed an active learning course that used free online platforms to teach physiology during a period in which undergraduates were not in classrooms or taking online classes due to the COVID-19 pandemic. Herein, we report the course organization and the students' involvement in, acceptance of, and evaluation of the course. To address the students' perceptions about these points, we sent a questionnaire to 49 participants who finished the course. We found that although most students (52.5%) had never taken a course with similar methods before, almost all of them (95%) liked the flipped class model. Additionally, a majority of the students (92.5%) said that the method increased their study frequency during the social distancing period, which is an important aspect to consider during this challenging time for both students and professors.

Relating human physiology content to COVID-19: a strategy to keep students in touch with physiology in times of social distance due to pandemic.

In 2020 universities had to quickly implement remote education alternatives as a result of the social distancing due to the COVID-19 pandemic. To keep students engaged with the university, we implemented a teaching-learning model that relates physiology contents to the COVID-19 pandemic using online educational platforms. A 1-mo web course was proposed for health sciences students from the Federal University of Pampa. It included synchronous meetings twice a week and asynchronous activities using scientific articles, case studies, and interactive online tools. The students approved the methodology developed, assessing it as dynamic and innovative. They reported that the activity helped to better understand the relations between COVID-19 and physiological systems. The web course also contributed to the identification of reliable sources of news and stimulated the sharing of scientific content with their families. We concluded that the use of online platforms contextualizing the physiology content considering current events helps students in learning human physiology and improves their abilities to apply this information to their daily life, in this specific case, regarding the COVID-19 pandemic.

Maternal Deprivation Induces Memory Deficits That Are Reduced by One Aerobic Exercise Shot Performed after the Learning Session.

During the neonatal period, the brain is susceptible to external influences. Exposure to stressful events during this phase of life influences brain development and impacts adult life. In animals, the maternal deprivation (MD) model is effective in mimicking stress in the early stages of development. In contrast, physical exercise seems to be able to prevent deficits in memory consolidation. Although the effects of chronic exercise in cognition are already well established, little is known about the effects of acute aerobic exercise. Here, male Wistar rats divided into deprived (MD) and nondeprived (NMD) rats were submitted to the object recognition (OR) memory test. Immediately after OR training, some of the rats were submitted to a single aerobic exercise session for 30 minutes. Memory consolidation and persistence were evaluated by retention tests performed 24 h and 7, 14, and 21 days after OR training. We show that a single physical exercise session is able to modulate learning by promoting memory consolidation and persistence in rats with cognitive deficits induced by MD. Hippocampal dopamine levels, measured by HPLC, were not altered after OR training in rats that performed and in rats that did not perform an exercise session; on the other hand, while OR training promoted increase of hippocampal norepinephrine in NMD rats, the MD rats did not present this increase, regardless of the practice or not of exercise.