Alzheimer’s disease (AD) is characterized by multiple cognitive deficits including memory and sensorimotor gating impairments as a result of neuronal and synaptic loss. The endocannabinoid system plays an important role in these deficits but little is known about its influence on the molecular mechanism regarding phosphorylated tau (p-tau) protein accumulation – one of the hallmarks of AD –, and on the density of synaptic proteins. Thus, the aim of this study was to investigate the preventive effects of anandamide (N-arachidonoylethanolamine, AEA) on multiple cognitive deficits and on the levels of synaptic proteins (syntaxin 1, synaptophysin and synaptosomal-associated protein, SNAP-25), cannabinoid receptor type 1 (CB1) and molecules related to p-tau degradation machinery (heat shock protein 70, HSP70), and Bcl2-associated athanogene (BAG2) in an AD-like sporadic dementia model in rats using intracerebroventricular (icv) injection of streptozotocin (STZ). Our hypothesis is that AEA could interact with HSP70, modulating the level of p-tau and synaptic proteins, preventing STZ-induced cognitive impairments. Thirty days after receiving bilateral icv injections of AEA or STZ or both, the cognitive performance of adult male Wistar rats was evaluated in the object recognition test, by the escape latency in the elevated plus maze (EPM), by the tone and context fear conditioning as well as in prepulse inhibition tests. Subsequently, the animals were euthanized and their brains were removed for histological analysis or for protein quantification by Western Blotting. The behavioral results showed that STZ impaired recognition, plus maze and tone fear memories but did not affect contextual fear memory and prepulse inhibition. Moreover, AEA prevented recognition and non-associative emotional memory impairments induced by STZ, but did not influence tone fear conditioning. STZ increased the brain ventricular area and this enlargement was prevented by AEA. Additionally, STZ reduced the levels of p-tau (Ser199/202) and increased p-tau (Ser396), although AEA did not affect these alterations. HSP70 was found diminished only by STZ, while BAG2 levels were decreased by STZ and AEA. Synaptophysin, syntaxin and CB1 receptor levels were reduced by STZ, but only syntaxin was recovered by AEA. Altogether, albeit AEA failed to modify some AD-like neurochemical alterations, it partially prevented STZ-induced cognitive impairments, changes in synaptic markers and ventricle enlargement. This study showed, for the first time, that the administration of an endocannabinoid can prevent AD-like effects induced by STZ, boosting further investigations about the modulation of endocannabinoid levels as a therapeutic approach for AD.

Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30–35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a “three-bottle choice” paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

Animal models have promoted meaningful contribution to science including Alzheimer's disease (AD) research. Several animal models for AD have been used, most of them related to genetic mutations observed in familial AD. However, sporadic form of AD, also named late-onset is the most frequent form of the disease, which is multifactorial, being influenced by genetic, environmental and lifestyle factors. Here, we describe a protocol of an AD-like pathology of the sporadic form using Wistar rats by a single bilateral intracerebroventricular (icv) injection of streptozotocin (STZ, 2 mg/kg). Icv injection of STZ induces brain resistance to insulin and other pathological alterations related to those observed in AD, such as cognitive impairment and accumulation of phosphorylated tau protein and β-amyloid in the brain. Thus, icv injection of STZ is a useful tool to investigate the pathological mechanisms and the metabolic alterations involved in AD and to propose new therapeutic approaches and neuroprotective drugs.

Coronavirus disease 2019 (COVID-19) is a viral pneumonia that can lead to acute respiratory distress syndrome (ARDS). Until the commercialization of a vaccine, pharmacological treatment still represents an important strategy to fight against the ongoing pandemic. Glucocorticoids (GC) were widely used in the past coronavirus pandemics and have been used against the coronavirus 2 severe acute respiratory syndrome (SARS-CoV-2). This article aimed to review the studies that described the treatment with GC in COVID-19 patients. Randomized or nonrandomized clinical trials and retrospective or prospective-controlled longitudinal studies were screened for this systematic review. Studies in English, Portuguese, and Spanish published since 2019, with participants of any clinical status, geographic location, age, and sex were included. The most significant interest was related to the length of stay, radiological profile changes, viremia, and mortality. The research was done electronically on the Pubmed database using the following terms: "corticosteroids", "glucocorticoids", "dexamethasone", "methylprednisolone", "COVID-19", "SARS-CoV-2", "ADRS". We identified 6332 publications, and at the end, 14 retrospective observational studies that met all the inclusion criteria were selected. These studies included only patients infected with SARS-CoV-2 confirmed by RT-PCR, involving 2,713 participants. The results showed great heterogeneity in their designs and results, which precludes a reliable conclusion on the use of GCs in the treatment of COVID-19.

The present study indicates that previous EtOH consumption as well as stress exposure induces increased EtOH conditioning, which can be related to dopaminergic alterations in the PFC or NAc. Interestingly, concomitant exposure to both stimuli abolished each other's effect on conditioning and PFC or NAc alterations. This protective outcome can be related to the dopaminergic increase in the amygdala.