While chronic stress induces learning and memory impairments, acute stress may facilitate or prevent memory consolidation depending on whether it occurs during the learning event or before it, ...respectively. On the other hand, it has been shown that histone acetylation regulates long-term memory formation. This study aimed to evaluate the effect of two inhibitors of class I histone deacetylases (HDACs), 4-phenylbutyrate (PB) and IN14 (100 mg/kg/day, ip for 2 days), on memory performance in mice exposed to a single 15-min forced swimming stress session. Plasma corticosterone levels were determined 30 minutes after acute swim stress in one group of mice. In another experimental series, independent groups of mice were trained in one of three different memory tasks: Object recognition test, Elevated T maze, and Buried food location test. Subsequently, the hippocampi were removed to perform ELISA assays for histone deacetylase 2 (HDAC2) expression. Acute stress induced an increase in plasma corticosterone levels, as well as hippocampal HDAC2 content, along with an impaired performance in memory tests. Moreover, PB and IN14 treatment prevented memory loss in stressed mice. These findings suggest that HDAC2 is involved in acute stress-induced cognitive impairment. None of the drugs improved memory in non-stressed animals, indicating that HDACs inhibitors are not cognitive boosters, but rather potentially useful drugs for mitigating memory deficits.
Severe dengue is characterized by thrombocytopenia, hemorrhaging, and/or capillary extravasation and may be linked to a reduced plasma concentration of serotonin (5-hydroxytriptamine, or 5-HT).
The ...aim of the current contribution was to conduct a systematic bibliographic review of reports on the role of the peripheral serotonergic system in the pathophysiology of severe dengue.
A bibliographic review was carried out of in vivo/in vitro models, clinical trials, and case series studies from 2010-2019. The selective criteria were the use of treatments with serotonin reuptake inhibitors and/or agonists/antagonists of 5-HT receptors and their impact on inflammation, coagulation, and endothelium. Moreover, cross-sectional and cohort studies on the relationship between intraplatelet and plasma 5-HT levels in patients with dengue were also included. The risk of bias in the selected reports was examined with domain-based assessment utilizing Cochrane-type criteria. The main results are summarized in Tables and Figures.
Based on descriptions of the effect of serotonergic drugs on 5-HT levels and the findings of clinical trials of dengue treatment, most receptors of the peripheral serotonergic system, and especially 5-HT2A, seem to participate in regulating serum 5-HT during severe dengue. Therefore, the peripheral serotonergic system probably contributes to thrombocytopenia and capillary extravasation.
Regarding dengue, 5-HT may be a key parameter for predicting severity, and an understanding of 5-HT-related mechanisms could possibly facilitate the development of new therapies. These proposals require further research due to the limited number of publications on the role of serotonergic receptors at the peripheral level.
This paper introduces the COVID-19 Open Dataset (COD), available at goo.gle/covid-19-open-data . A static copy is of the dataset is also available at https://doi.org/10.6084/m9.figshare.c.5399355 . ...This is a very large "meta-dataset" of COVID-related data, containing epidemiological information, from 22,579 unique locations within 232 different countries and independent territories. For 62 of these countries we have state-level data, and for 23 of these countries we have county-level data. For 15 countries, COD includes cases and deaths stratified by age or sex. COD also contains information on hospitalizations, vaccinations, and other relevant factors such as mobility, non-pharmaceutical interventions and static demographic attributes. Each location is tagged with a unique identifier so that these different types of information can be easily combined. The data is automatically extracted from 121 different authoritative sources, using scalable open source software. This paper describes the format and construction of the dataset, and includes a preliminary statistical analysis of its content, revealing some interesting patterns.
Serotonin (5-hydroxytryptamine; C(10)H(12)N(2)O (5-HT)) is produced in the CNS and in some cells of peripheral tissues. In the mammalian male reproductive system, both 5-HT and tryptophan hydroxylase ...(TPH) have been described in Leydig cells of the testis and in principal cells of the caput epididymis. In capacitated hamster sperm, it has been shown that 5-HT promotes the acrosomal reaction. The aim of this work was to explore the existence of components of the serotoninergic system and their relevance in human sperm physiology. We used both immunocytochemistry and western blot to detect serotoninergic markers such as 5-HT, TPH1, MAO(A), 5-HT(1B), 5-HT(3), and 5HT(T); HPLC for TPH enzymatic activity; Computer Assisted Semen Analysis assays to measure sperm motility parameters and pharmacological approaches to show the effect of 5-HT in sperm motility and tyrosine phosphorylation was assessed by western blot. We found the presence of serotoninergic markers (5-HT, TPH1, MAO(A), 5-HT(1B), 5-HT(2A), 5-HT(3), 5-HT(T), and TPH enzymatic activity) in human sperm. In addition, we observed a significant increase in tyrosine phosphorylation and changes in sperm motility after 5-HT treatment. In conclusion, our data demonstrate the existence of components of a serotoninergic system in human sperm and support the notion for a functional role of 5-HT in mammalian sperm physiology, which can be modulated pharmacologically.
Evidence suggests that histone deacetylases (HDACs) inhibitors could be used as an effective treatment for some psychiatric and neurological conditions such as depression, anxiety and age-related ...cognitive decline. However, non-specific HDAC inhibiting compounds have a clear disadvantage regarding their efficacy and safety, thus the need to develop more selective ones. The present study evaluated the toxicity, the capacity to inhibit HDAC activity and antidepressant-like activity of three recently described class I HDAC inhibitors IN01, IN04 and IN14, using
toxicity test,
fluorometric HDAC activity assay and forced-swimming test, respectively. Our data show that IN14 possesses a better profile than the other two. Therefore, the pro-cognitive and antidepressant effects of IN14 were evaluated. In the forced-swimming test model of depression, intraperitoneal administration of IN14 (100 mg/Kg/day) for five days decreased immobility, a putative marker of behavioral despair, significantly more than tricyclic antidepressant desipramine, while also increasing climbing behavior, a putative marker of motivational behavior. On the other hand, IN14 left the retention latency in the elevated T-maze unaltered. These results suggest that novel HDAC class I inhibitor IN14 may represent a promising new antidepressant with low toxicity and encourages further studies on this compound.
The aim of this study was to explore the influence of short-term (2-week) exposure to social (SE) and/or physical enrichment (PE) on the anxiety-like behavior of ovariectomized (OVX) NIH Swiss mice.
...One week after surgery, each OVX mouse was housed under one of 4 social conditions: (1) isolated, (2) accompanied by an intact female, (3) accompanied by an intact male, or (4) in a community of 10 OVX individuals. The animals in each of these environments were divided into 2 subgroups, consisting of the presence and absence of PE. Following a 2-week exposure to the respective conditions, each OVX mouse was subjected to either the light/dark exploration test (LDT) or the elevated plus maze (EPM) to examine anxiety-like behavior.
The LDT and EPM showed very similar patterns. Compared to an impoverished environment, PE elicited a significant anxiolytic effect for OVX mice housed alone or in companion of an intact female (F 1, 54 = 16.11, P = 0.001). By contrast, mice living in community but without PE displayed anxiogenic-like behavior, perhaps due to crowding, compared to the animals living in isolation (F 1, 36 = 5.64, P = 0.023).
This study emphasized the importance of taking housing conditions into account during the screening of new anxiolytic agents and the critical role of OVX in the regulation of anxiety.
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The development of potent and selective dopamine receptors (D2DR) ligands is an attractive task. In this work, we designed boron containing arylethanolamine derivatives from a molecular ...docking study on D2 receptor models. We selected and synthesized the boron containing compound 5‐(2‐ammonioethyl)‐2,2‐ dihydroxybenzod1,3,2dioxaborol‐2‐uide and its chemical characterization was done. The intraperitoneal administration of this compound slightly disrupted the locomotor activity of CD1 or C57‐BL/6 mice. However, locomotor deficit induced by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP, a neurotoxin which damages dopaminergic neurons in the substantia nigra) in an acute regimen on C57‐BL/6 mice, was reverted in the first 24h, after the new compound administration. Altogether, results strongly suggest that this new compound acts as an agonist on the dopaminergic system of mice. This work was partially supported by grants from SIP‐IPN, CONACYT and INNOVAPyME/CONACyT programs.
Neurosurgical treatment, although controversial, is considered a useful resource in the treatment of chronic psychiatric diseases such as refractory aggressiveness.
To evaluate the clinical results ...and side effects of posteromedial hypothalamotomy associated with amygdalotomy in patients with refractory aggressiveness.
A clinical trial was conducted in patients with chronic aggressiveness and refractory to pharmacological treatment. A central amygdalotomy associated with posteromedial hypothalamotomy was performed using thermo-coagulation by radiofrequency. The degree of aggressiveness was quantified by the Yudofsky's global scale of aggression. Postoperative changes in aggressive behavior continued to be evaluated every 6 months for at least 36 months.
A statistically significant change in aggressive behavior was observed during 36 months of follow-up. The collateral effects of the association of both procedures are described, the most frequent being drowsiness and some cases of reduction in sexual behavior.
Symmetric and simultaneous unilateral lesions of the central nucleus of the amygdala and the posteromedial hypothalamus contralateral to motor dominance give the same clinical effect in the reduction of the pathological aggression that the bilateral lesions.
Forced swimming induces alterations in the GABA brain concentration and could change the sensitivity of the GABA/benzodiazepine receptor–chloride ionophore complex to benzodiazepines. This change in ...sensitivity could be explained by the allopregnanolone release that takes place during stress. The current study was carried out to determine whether forced swimming is able to modify the anti-anxiety effect of diazepam and to explore the possible relation of this change to allopregnanolone, the GABA concentration or/and the GABA/benzodiazepine receptor density.
Unstressed and stressed mice, injected with the vehicle or diazepam, were evaluated in the exploratory behavior test. Diazepam induced clear anxiolytic actions at all doses in unstressed animals, but such an effect was not observed in stressed animals. The injection of allopregnanolone 24 h before the anxiety test blocked the effect of this benzodiazepine. Forced swimming decreased GABA concentrations in the hippocampus and the thalamus–hypothalamus region, besides decreasing the
3Hflunitrazepam labeling in both the hypothalamus and amygdala.
These results show that forced swimming abolishes the anti-anxiety effect of diazepam.
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