Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT receptor.

Schizophrenia is a chronic disease affecting 1% worldwide population, of which 30% are refractory to the available treatments: thus, searching for new pharmacological targets is imperative. The acute and repeated ketamine administration are validated preclinical models that recreate the behavioral and neurochemical features of this pathology, including the parvalbumin-expressing interneurons dysfunction. Angiotensin II, through AT receptors (AT-R), modulates the dopaminergic and GABAergic neurotransmission.

A poor and delayed anti-SARS-CoV2 IgG response is associated to severe COVID-19 in children.

Background: Most children and youth develop mild or asymptomatic disease during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, a very small number of patients suffer severe Coronavirus induced disease 2019 (COVID-19). The reasons underlying these different outcomes remain unknown.

Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury.

Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality in adults under 40 years old. Once primary injury occurs after TBI, neuroinflammation and oxidative stress (OS) are triggered, contributing to the development of many TBI-induced neurological deficits, and reducing the probability of critical trauma patients´ survival. Regardless the research investment on the development of anti-inflammatory and neuroprotective treatments, most pre-clinical studies have failed to report significant effects, probably because of the limited blood brain barrier permeability of no-steroidal or steroidal anti-inflammatory drugs.

Blood neutrophils from children with COVID-19 exhibit both inflammatory and anti-inflammatory markers.

Background: Perhaps reflecting that children with COVID-19 rarely exhibit severe respiratory symptoms and often remain asymptomatic, little attention has been paid to explore the immune response in pediatric COVID-19. Here, we analyzed the phenotype and function of circulating neutrophils from children with COVID-19.

Methods: An observational study including 182 children with COVID-19, 21 children with multisystem inflammatory syndrome (MIS-C), and 40 healthy children was performed in Buenos Aires, Argentina.

Poloxamer 188-Coated Ammonium Methacrylate Copolymer Nanocarriers Enhance Loperamide Permeability across Pgp-Expressing Epithelia.

Loperamide is a μ-opioid agonist with poor gastrointestinal absorption, mainly because of its modest aqueous solubility and being a P-glycoprotein (Pgp) efflux substrate. Nevertheless, studies associated with therapeutic effects strongly suggest that loperamide holds potential pharmacological advantages over traditional μ-opioid agonists commonly used for analgesia. Thus, in this Communication, we assessed in MDCK-hMDR1 cell lines the effects over loperamide uptake and efflux ratio, when loaded into Eudragit RS (ERS) nanocarriers coated with poloxamer 188 (P188).

Early Cognitive Impairment Behind Nigrostriatal Circuit Neurotoxicity: Are Astrocytes Involved?

Cognitive dysfunction is one of the most severe nonmotor symptoms of nigrostriatal impairment. This occurs as a result of profound functional and morphological changes of different neuronal circuits, including modifications in the plasticity and architecture of hippocampal synapses. Such alterations can be implicated in the genesis and progression of dementia associated with neurodegenerative diseases including Parkinson-like symptoms.

Pharmacological NOS-1 Inhibition Within the Hippocampus Prevented Expression of Cocaine Sensitization: Correlation with Reduced Synaptic Transmission.

Behavioral sensitization to psychostimulants hyperlocomotor effect is a useful model of addiction and craving. Particularly, cocaine sensitization in rats enhanced synaptic plasticity within the hippocampus, an important brain region for the associative learning processes underlying drug addiction. Nitric oxide (NO) is a neurotransmitter involved in both, hippocampal synaptic plasticity and cocaine sensitization.

Cognitive interference as a possible therapeutic strategy to prevent expression of benzodiazepine withdrawal.

Benzodiazepines are usually prescribed for anxiety and sleep disorders in long-term schedules that may cause drug dependence. Discontinuation after prolonged administration may lead to withdrawal expression, being anxiety the most predominant sign. The context-dependent associative learning process that underlies diazepam dependence can be interfered by pre-exposure to the drug administration context, an effect known as latent inhibition.

Selective Photoinduced Antibacterial Activity of Amoxicillin-Coated Gold Nanoparticles: From One-Step Synthesis to in Vivo Cytocompatibility.

Photoinduced antibacterial gold nanoparticles were developed as an alternative for the treatment of antibiotic-resistant bacteria. Thanks to the amoxicillin coating, they possess high in vivo stability, selectivity for the bacteria wall, a good renal clearance, and are completely nontoxic for eukaryotic cells at the bactericidal concentrations. A simple one-step synthesis of amoxi@AuNP is described at mild temperatures using the antibiotic as both reducing and stabilizing agent.

Tetrahydrobiopterin improves hippocampal nitric oxide-linked long-term memory.

Tetrahydrobiopterin (BH4) is synthesized by the combined action of three metabolic pathways, namely de novo synthesis, recycling, and salvage pathways. The best-known function of BH4 is its mandatory action as a natural cofactor of the aromatic amino acid hydroxylases and nitric oxide synthases. Thus, BH4 is essential for the synthesis of nitric oxide, a retrograde neurotransmitter involved in learning and memory.

Reduced vasopressin receptors activation mediates the anti-depressant effects of fluoxetine and venlafaxine in bulbectomy model of depression.

Rationale: In response to stress, corticotropin releasing hormone (CRH) and vasopressin (AVP) are released from the hypothalamus, activate their receptors (CRHR1, CRHR2 or AVPr1b), and synergistically act to induce adrenocorticotropic hormone (ACTH) release from the anterior pituitary. Overstimulation of this system has been frequently associated with major depression states.

Objective: The objective of the study is to assess the role of AVP and CRH receptors in fluoxetine and venlafaxine effects on the expression of depression-related behavior.

Brain Angiotensin II AT1 receptors are involved in the acute and long-term amphetamine-induced neurocognitive alterations.

Rationale: Angiotensin II, by activation of its brain AT1-receptors, plays an active role as neuromodulator in dopaminergic transmission. These receptors participate in the development of amphetamine-induced behavioral and dopamine release sensitization. Dopamine is involved in cognitive processes and provides connectivity between brain areas related to these processes.

Involvement of nNOS/NO/sGC/cGMP signaling pathway in cocaine sensitization and in the associated hippocampal alterations: does phosphodiesterase 5 inhibition help to drug vulnerability?

Rationale: Repeated cocaine administration induces behavioral sensitization in about 50 % of treated animals. Nitric oxide could be involved in the acquisition and maintenance of behavioral cocaine effects, probably by activation of neuronal nitric oxide synthase (nNOS)/NO/soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) signaling pathway, since inhibition of the nNOS enzyme attenuates development of sensitization in rats. On the other hand, increased cGMP availability by phosphodiesterase 5 inhibitors has been correlated to the misuse and recreational use of these agents and also to the concomitant use with illicit drugs in humans.

Impact of contextual cues in the expression of the memory associated with diazepam withdrawal: involvement of hippocampal PKMζ in vivo, and Arc expression and LTP in vitro.

Hippocampal synaptic plasticity has been related to learning and adaptive processes developed during chronic drug administration, suggesting the existence of a common neurobiological mechanism mediating drug addiction and memory. Moreover, protein kinase M zeta (PKMζ) is critical for the maintenance of hippocampal long-term potentiation (LTP) and spatial conditioned long-term memories. Also, a link between activity-regulated cytoskeleton-associated protein (Arc), PKMζ and LTP has been proposed.

Inhibition of neuronal nitric oxide synthase prevents alterations in medial prefrontal cortex excitability induced by repeated cocaine administration.

Rationale: The medial prefrontal cortex (mPFC), a forebrain region that regulates cognitive function and reward-motivated behaviors, has been implicated in the neuropathological mechanisms of drug addiction and withdrawal. In cocaine-abstinent human addicts, neuronal activity of the mPFC is increased in response to cocaine re-exposure or drug-associated cues. Additionally, repeated cocaine exposure alters the membrane properties and ion channel function of mPFC pyramidal neurons in drug-withdrawn rats, leading to an increased firing in response to excitatory stimuli.

Repeated cocaine exposure decreases dopamine D₂-like receptor modulation of Ca(2+) homeostasis in rat nucleus accumbens neurons.

The nucleus accumbens (NAc) is a limbic structure in the forebrain that plays a critical role in cognitive function and addiction. Dopamine modulates activity of medium spiny neurons (MSNs) in the NAc. Both dopamine D₁-like and D₂-like receptors (including D1R or D(1,5)R and D2R or D(2,3,4)R, respectively) are thought to play critical roles in cocaine addiction.

The intra-hippocampal leucine administration impairs memory consolidation and LTP generation in rats.

Leucine accumulates in fluids and tissues of patients affected by maple syrup urine disease, an inherited metabolic disorder, predominantly characterized by neurological dysfunction. Although, a variable degree of cognition/psychomotor delay/mental retardation is found in a considerable number of individuals affected by this deficiency, the mechanisms underlying the neuropathology of these alterations are still not defined. Therefore, the aim of this study was to investigate the effect of acute intra-hippocampal leucine administration in the step-down test in rats.

Ghrelin induced memory facilitation implicates nitric oxide synthase activation and decrease in the threshold to promote LTP in hippocampal dentate gyrus.

Although the hypothalamus has been long considered the main ghrelin (Ghr) target organ mediating orexigenic effects, recently it has been shown that in-vivo Ghr hippocampus administration improves learning and memory in the inhibitory avoidance paradigm. However, the possible mechanisms underlying this memory facilitation effect have not been clarified. Given that the biochemical memory cascade into the hippocampus involves nitric oxide (NO) synthesis via NO synthase (NOS) activation, we investigated 1) if Ghr administration modulated NOS activity in the hippocampus; and 2) if hippocampal NOS inhibition influenced Ghr-induced memory facilitation, using a behavioral paradigm, biochemical determinations and an electrophysiological model.

Dopamine D(2) receptor modulation of K(+) channel activity regulates excitability of nucleus accumbens neurons at different membrane potentials.

The nucleus accumbens (NAc) is a forebrain area in the mesocorticolimbic dopamine (DA) system that regulates many aspects of drug addiction. Neuronal activity in the NAc is modulated by different subtypes of DA receptors. Although DA signaling has received considerable attention, the mechanisms underlying D(2)-class receptor (D(2)R) modulation of firing in medium spiny neurons (MSNs) localized within the NAc remain ambiguous.

Hippocampal synaptic plasticity in mice devoid of cellular prion protein.

The cellular prion protein plays a role in the etiology of transmissible and inherited spongiform encephalopathies. However, the physiological role of the cellular prion protein is still under debate. Results regarding the synaptic transmission using the same strain of animals where the cellular prion protein gene was ablated are controversial, and need further investigation.

MK-801 prevents the increased NMDA-NR1 and NR2B subunits mRNA expression observed in the hippocampus of rats tolerant to diazepam.

The chronic diazepam administration in rats has been show from our previous results, to produce an increased synaptic plasticity. Furthermore, this occurs with a concomitant over expression of the mRNA NR1 and NR2B N-methyl-D-aspartate receptor subunits. MK-801, a non-competitive antagonist of N-methyl-D-aspartate receptor, impairs both the development of conditioned tolerance to diazepam and the hippocampal long-term potentiation generation.

Increased susceptibility to LTP generation and changes in NMDA-NR1 and -NR2B subunits mRNA expression in rat hippocampus after MCH administration.

The present study attempts to determine which mechanisms underlie the retrograde facilitation of memory induced by microinjection hippocampal melanin-concentrating hormone (MCH) on the inhibitory avoidance paradigm. Previous reports using this test on the hippocampus suggest that NMDA receptor-mediated mechanisms are involved in memory processing and are also necessary for the induction of long-term potentiation (LTP) of the hippocampal dentate gyrus. In addition, alterations in expression of synaptic NMDA subunits in the hippocampus have been associated with memory formation of an inhibitory avoidance task.