Isolation and characterization of neurotoxic astrocytes derived from adult triple transgenic Alzheimer's disease mice.

Alzheimer's disease has been considered mostly as a neuronal pathology, although increasing evidence suggests that glial cells might play a key role in the disease onset and progression. In this sense, astrocytes, with their central role in neuronal metabolism and function, are of great interest for increasing our understanding of the disease. Thus, exploring the morphological and functional changes suffered by astrocytes along the course of this disorder has great therapeutic and diagnostic potential.

Multitarget 2'-hydroxychalcones as potential drugs for the treatment of neurodegenerative disorders and their comorbidities.

The complex nature of neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD) and Parkinson's disease (PD) calls for multidirectional treatment. Restoring neurotransmitter levels by combined inhibition of cholinesterases (ChEs) and monoamine oxidases (MAOs, MAO-A and MAO-B), in conjunction with strategies to counteract amyloid β (Aβ) aggregation, may constitute a therapeutically strong multi-target approach for the treatment of NDDs. Chalcones are a subgroup of flavonoids with a broad spectrum of biological activity.

CD300f immunoreceptor is associated with major depressive disorder and decreased microglial metabolic fitness.

A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD), has been postulated. Regulation of microglial phenotype by immune receptors has become a central topic in many neurological conditions. We explored preclinical and clinical evidence for the role of the CD300f immune receptor in the fine regulation of microglial phenotype and its contribution to MDD.

Efficacy and safety of a novel nitric oxide generator for the treatment of neonatal pulmonary hypertension: Experimental and clinical studies.

Persistent pulmonary hypertension of the newborn (PPHN) is a complex pathology resulting from a failure of the post-natal reduction in pulmonary vascular resistance leading to hypoxemia. The standard therapy is inhaled Nitric Oxide (NO) improving oxygenation but its availability is limited, especially in hospitals with restricted financial resources. We evaluated the efficacy and safety of a new device generating NO (TAS + PLUS), in three experimental piglet models of pulmonary hypertension (PH), and we later tested its application in a pilot study of newborn patients suffering from PPHN.

Alterations in the Gut Microbiota of Rats Chronically Exposed to Volatilized Cocaine and Its Active Adulterants Caffeine and Phenacetin.

A role of the gut microbiota in influencing brain function and emotional disorders has been suggested. However, only a few studies have investigated the gut microbiota in the context of drug addiction.Cocaine can be smoked (i.

Nicotine-Induced Neuroprotection in Rotenone In Vivo and In Vitro Models of Parkinson's Disease: Evidences for the Involvement of the Labile Iron Pool Level as the Underlying Mechanism.

Parkinson's disease (PD) is characterized by the degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). Clinical and experimental evidence suggest that the activation of the nicotinic acetylcholine receptor (nAChR) could be protective for PD. In this study, we investigated the neuroprotective capacity of nicotine in a rat PD model.

Identification and Quantification of Cocaine and Active Adulterants in Coca-Paste Seized Samples: Useful Scientific Support to Health Care.

Adulteration is a common practice in the illicit drugs market, but the psychoactive and toxic effects provided by adulterants are clinically underestimated. Coca-paste (CP) is a smokable form of cocaine which has an extremely high abuse liability. CP seized samples are sold adulterated; however, qualitative and quantitative data of CP adulteration in forensic literature is still scarce.

Caffeine Induces a Stimulant Effect and Increases Dopamine Release in the Nucleus Accumbens Shell Through the Pulmonary Inhalation Route of Administration in Rats.

Oral, intraperitoneal, or intravenous have been the common routes of administration used to study the behavioral and neurochemical pharmacology of caffeine, one of the most widely used psychoactive substances worldwide. We have reported that caffeine is an active adulterant frequently found in coca-paste (CP)-seized samples, a highly addictive form of smokable cocaine. The role of caffeine in the psychostimulant and neurochemical effects induced by CP remains under study.

Caffeine, a common active adulterant of cocaine, enhances the reinforcing effect of cocaine and its motivational value.

Rationale: Caffeine is one of the psychoactive substances most widely used as an adulterant in illicit drugs, such as cocaine. Animal studies have demonstrated that caffeine is able to potentiate several cocaine actions, although the enhancement of the cocaine reinforcing property by caffeine is less reported, and the results depend on the paradigms and experimental protocols used.

Objectives: We examined the ability of caffeine to enhance the motivational and rewarding properties of cocaine using an intravenous self-administration paradigm in rats.

Quercetin in brain diseases: Potential and limits.

Quercetin is a ubiquitous flavonoid present in beverages, food and plants that has been demonstrated to have a role in the prevention of neurodegenerative and cerebrovascular diseases. In neuronal culture, quercetin increases survival against oxidative insults. Antioxidation appears to be a necessary but not sufficient condition for its neuroprotective action and modulation of intracellular signaling and transcription factors, increasing the expression of antioxidant and pro survival proteins and modulating inflammation, appears as important for neuronal protection.

Antioxidant activity, cellular bioavailability, and iron and calcium management of neuroprotective and nonneuroprotective flavones.

Few studies have been undertaken on the relationship of the structure of flavones and neuroprotection. Previously, we described the structural determinants of the neuroprotective activity of some natural flavones in cerebellar granule neurons in culture against an oxidative insult (H2O2). In the present work, we analyzed anti-oxidant activity, cellular iron, and Ca(2+) levels and cellular bioavailability of neuroprotective and nonneuroprotective flavones in the same experimental paradigm.

Anti-aggressive effect elicited by coca-paste in isolation-induced aggression of male rats: influence of accumbal dopamine and cortical serotonin.

Coca-paste (CP), an illicit drug of abuse, has been frequently associated with aggressive and impulsive behaviors in humans. However, preclinical studies have not been carried out in order to characterize CP effects on aggression. The acute effect of CP, cocaine and caffeine (the main adulterant present in seized samples) on aggression was assessed using the isolation-induced aggression paradigm in male rats.

Identification and structural characterization of serobactins, a suite of lipopeptide siderophores produced by the grass endophyte Herbaspirillum seropedicae.

Herbaspirillum seropedicae Z67 is a diazotrophic endophyte able to colonize the interior of many economically relevant crops such as rice, wheat, corn and sorghum. Structures of siderophores produced by bacterial endophytes have not yet been elucidated. The aim of this work was to identify and characterize the siderophores produced by this bacterium.

Genotoxic and antigenotoxic activity of acerola (Malpighia glabra L.) extract in relation to the geographic origin.

Malpighia glabra L, popularly known as acerola, is considered a functional fruit and therefore is taken to prevent disease or as adjuvant to treatment strategies, since the fruit is an undeniable source of vitamin C, carotenoids, and flavonoids. Acerola is a natural source of vitamin C, flavonoids, and carotenoids. Its chemical composition is affected by genetic uniformity of the orchards and environmental factors.

Antigenotoxicity and antioxidant activity of Acerola fruit (Malpighia glabra L.) at two stages of ripeness.

Genotoxic and antigenotoxic effects of acerola fruit at two stages of ripeness were investigated using mice blood cells. The results show that no ripeness stage of acerola extracts presented any genotoxic potential to damage DNA (Comet assay) or cytotoxicity (MTT assay). When antigenotoxic activity was analyzed, unripe fruit presented higher DNA protection than ripe fruit (red color) extract.

Coca-paste seized samples characterization: chemical analysis, stimulating effect in rats and relevance of caffeine as a major adulterant.

Coca-paste (CP) is a drug of abuse that so far has not been extensively characterized. CP is an intermediate product of the cocaine alkaloid extraction process from coca leaves, hence it has a high content of cocaine base mixed with other chemical substances (impurities) and it is probably adulterated when it reaches the consumers. Despite its high prevalence and distribution through South America, little is known about its effects on the central nervous system.

In silico characterization of cytisinoids docked into an acetylcholine binding protein.

Homology models of nicotinic acetylcholine receptors (nAChRs) suggest that subtype specificity is due to non-conserved residues in the complementary subunit of the ligand-binding pocket. Cytisine and its derivatives generally show a strong preference for heteromeric alpha4beta2* nAChRs over the homomeric alpha7 subtype, and the structural modifications studied do not cause large changes in their nAChR subtype selectivity. In the present work we docked cytisine, N-methylcytisine, and several pyridone ring-substituted cytisinoids into the crystallographic structure of the Lymnaea stagnalis acetylcholine binding protein (AChBP) co-crystallized with nicotine (1UW6).

Increase in locomotor activity after acute administration of the nicotinic receptor agonist 3-bromocytisine in rats.

Nicotinic acetylcholine receptors influence striatal dopaminergic activity and its outcome on motor behavior. For these reasons, nicotinic receptors have been considered as therapeutically relevant targets for Parkinson's disease, in which a dramatic loss of dopamine affects motor functions. The aim of the present work was to compare the effects on locomotor activity induced by the nicotinic agonist cytisine and two brominated derivatives, 5- and 3-bromocytisine (5-BrCy and 3-BrCy) using nicotine for comparison.

Pretreatment with natural flavones and neuronal cell survival after oxidative stress: a structure-activity relationship study.

Quercetin shows structural features that have been related to the antioxidant potency of flavonoids and also shows neuroprotection in different models of oxidative death. Because only a few studies have focused on the flavonoid structural requirements for neuroprotection, this work evaluated the protective capacity of 13 flavones structurally related to quercetin, isolated from Kenyan plants, to rescue primary cerebellar granule neurons from death induced by a treatment with 24 h of hydrogen peroxide (150 microM). Each flavone (0-100 microM) was applied 24 h prior to the oxidative insult, and neuronal viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

Nicotine induces tyrosine hydroxylase plasticity in the neurodegenerating striatum.

It has been shown that nicotine prevents the loss of dopamine (DA) in the corpus striatum (CS) after 6-hydroxydopamine injection in the substantia nigra. To study the role of the enzyme tyrosine hydroxylase (TH; EC 1.14.

Cytoprotection by neutral fraction of tannat red wine against oxidative stress-induced cell death.

Some of the beneficial effects of the Mediterranean diet on human pathologies have been attributed to red wine polyphenols. It has been postulated that the antioxidant activity of the latter would be also responsible for the cytoprotective capacity of red wine that has been reported in a few papers. Nevertheless, red wine shows a complex composition, and the active fraction is not known yet.