Unveiling Niaprazine's Potential: Behavioral Insights into a Re-Emerging Anxiolytic Agent.

Ongoing global research actions seek to comprehensively understand the adverse impact of stress and anxiety on the physical and mental health of both human beings and animals. Niaprazine (NIA) is a chemical compound that belongs to the class of piperazine derivatives. This compound has recently gained renewed attention due to its potential therapeutic properties for treating certain conditions such as anxiety.

Muscarinic Receptors and Alzheimer's Disease: New Perspectives and Mechanisms.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases on a global scale. Historically, this pathology has been linked to cholinergic transmission, and despite the scarcity of effective therapies, numerous alternative processes and targets have been proposed as potential avenues for comprehending this complex illness. Nevertheless, the fundamental pathophysiological mechanisms underpinning AD remain largely enigmatic, with a growing body of evidence advocating for the significance of muscarinic receptors in modulating the brain's capacity to adapt and generate new memories.

Complement tunes glutamate release and supports synaptic impairments in an animal model of multiple sclerosis.

Background And Purpose: To deepen our knowledge of the role of complement in synaptic impairment in experimental autoimmune encephalomyelitis (EAE) mice, we investigated the distribution of C1q and C3 proteins and the role of complement as a promoter of glutamate release in purified nerve endings (synaptosomes) and astrocytic processes (gliosomes) isolated from the cortex of EAE mice at the acute stage of the disease (21 ± 1 day post-immunization).

Experimental Approach: EAE cortical synaptosomes and gliosomes were analysed for glutamate release efficiency (measured as release of preloaded [H]D-aspartate ([H]D-ASP)), C1q and C3 protein density, and for viability and ongoing apoptosis.

Key Results: In healthy mice, complement releases [H]D-ASP from gliosomes more efficiently than from synaptosomes.

Correction: Prophylactic versus Therapeutic Fingolimod: Restoration of Presynaptic Defects in Mice Suffering from Experimental Autoimmune Encephalomyelitis.

[This corrects the article DOI: 10.1371/journal.pone.

Progress in metamodulation and receptor-receptor interaction: From physiology to pathology and therapy.

The organization and the role of receptor-receptor interaction (RRI) and metamodulation in physiological conditions have been extensively analyzed and discussed. In this Special Issue of Neuropharmacology, we review recent advances in the understanding of the RRI and the mechanisms underlying its adaptation that could be relevant to the etiopathogenesis of central neuropsychiatric disorders, as well as to the development of new therapeutic approaches to control the activity and to restore the physiological functions, posing the basis for new targeted pharmacological interventions.

Metamodulation of presynaptic NMDA receptors: New perspectives for pharmacological interventions.

Metamodulation shifted the scenario of the central neuromodulation from a simplified unimodal model to a multimodal one. It involves different receptors/membrane proteins physically associated or merely colocalized that act in concert to control the neuronal functions influencing each other. Defects or maladaptation of metamodulation would subserve neuropsychiatric disorders or even synaptic adaptations relevant to drug dependence.

Central nervous system interaction and crosstalk between nAChRs and other ionotropic and metabotropic neurotransmitter receptors.

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed in both the peripheral and the central nervous systems. nAChRs exert a crucial modulatory influence on several brain biological processes; they are involved in a variety of neuronal diseases including Parkinson's disease, Alzheimer's disease, epilepsy, and nicotine addiction. The influence of nAChRs on brain function depends on the activity of other neurotransmitter receptors that co-exist with nAChRs on neurons.

Anxiety and Metabolic Disorders: The Role of Botanicals.

Anxiety and anxiety-related disorders are becoming more evident every day, affecting an increasing number of people around the world. Metabolic disorders are often associated with anxiety. Furthermore, anxiety branches into metabolic disorders by playing multiple roles as a cofactor, symptom, and comorbidity.

Presynaptic 5-HT-mGlu2/3 Receptor-Receptor Crosstalk in the Prefrontal Cortex: Metamodulation of Glutamate Exocytosis.

The glutamatergic nerve endings of a rat prefrontal cortex (PFc) possess presynaptic 5-HT heteroreceptors and mGlu2/3 autoreceptors, whose activation inhibits glutamate exocytosis, and is measured as 15 mM KCl-evoked [H]D-aspartate ([H]D-asp) release (which mimics glutamate exocytosis). The concomitant activation of the two receptors nulls their inhibitory activities, whereas blockade of the 5-HT heteroreceptors with MDL11,939 (1 μM) strengthens the inhibitory effect elicited by the mGlu2/3 receptor agonist LY329268 (1 μM). 5-HT receptor antagonists (MDL11,939; ketanserin; trazodone) amplify the impact of low (3 nM) LY379268.

The Anti-Aggregative Peptide KLVFF Mimics Aβ1-40 in the Modulation of Nicotinic Receptors: Implications for Peptide-Based Therapy.

In recent years, the inhibition of beta-amyloid (Aβ) aggregation has emerged as a potential strategy for Alzheimer's disease. KLVFF, a small peptide corresponding to the aminoacidic sequence 16-20 of Aβ, reduces Aβ fibrillation dose dependently. Therefore, the toxic and functional characterization of its brain activity is fundamental for clarifying its potential therapeutic role.

Use of an Animal Model to Evaluate Anxiolytic Effects of Dietary Supplementation with Moench Bud Extracts.

Anxiety disorders are common and complex psychiatric syndromes affecting a broad spectrum of patients. On top of that, we know that aging produces an increase in anxiety vulnerability and sedative consumption. Moreover, stress disorders frequently show a clear gender susceptibility.

Bud-Derivatives, a Novel Source of Polyphenols and How Different Extraction Processes Affect Their Composition.

The use of herbal food supplements, as a concentrate form of vegetable extracts, increased so much over the past years to count them among the relevant sources of dietetic polyphenols. Bud-derivatives are a category of botanicals perceived as a "new entry" in this sector since they are still poorly studied. Due to the lack of a manufacturing process specification, very different products can be found on the market in terms of their polyphenolic profile depending on the experimental conditions of manufacturing.

Neuroinflammation in Aged Brain: Impact of the Oral Administration of Ellagic Acid Microdispersion.

The immune system and the central nervous system message each other to preserving central homeostasis. Both systems undergo changes during aging that determine central age-related defects. Ellagic acid (EA) is a natural product which is beneficial in both peripheral and central diseases, including aging.

Ellagic acid a multi-target bioactive compound for drug discovery in CNS? A narrative review.

It is well-known that the health properties attributed to several fruits, herbs, seeds and their processed foods/beverages are due to an important group of natural polyphenols classified as hydrolysable tannins (HT) named ellagitannins (ETs), that encompass both one or more gallic acid (GA) units and one or more hexahydroxydiphenoic acid (HHDP) units, ester-connected with a sugar residue. In vivo, ETs are rather not absorbed and in gastrointestinal tract (GIT), they are hydrolysed providing mainly ellagic acid (EA). Due to its trivial water-solubility, first pass effect, metabolism in GIT, or irreversible binding to cellular DNA and proteins, EA has a very low bioavailability.

Beta-amyloid short- and long-term synaptic entanglement.

Beta-amyloid (Aβ) is a peptide that derives from the proteolytic cleavage of the amyloid precursor protein (APP) by several secretases. Since its isolation and sequencing from Alzheimer's disease (AD) brains, Aβ has been intensively investigated in the context of AD as the main pathogenic marker responsible for neurodegenerative processes. During the last three decades, results from several independent studies have converged to form the so-called amyloid cascade hypothesis of AD and several therapeutic strategies designed to modulate the APP amyloidogenic pathway have been developed.

5-HT-mGlu2/3 receptor complex in rat spinal cord glutamatergic nerve endings: A 5-HT to mGlu2/3 signalling to amplify presynaptic mechanism of auto-control of glutamate exocytosis.

Presynaptic mGlu2/3 autoreceptors exist in rat spinal cord nerve terminals as suggested by the finding that LY379268 inhibited the 15 mM KCl-evoked release of [H]D-aspartate ([H]D-Asp) in a LY341495-sensitive manner. Spinal cord glutamatergic nerve terminals also possess presynaptic release-regulating 5-HT heteroreceptors. Actually, the 15 mM KCl-evoked [H]D-Asp exocytosis from spinal cord synaptosomes was reduced by the 5-HT agonist (±)DOI, an effect reversed by the 5-HT antagonists MDL11,939, MDL100907, ketanserin and trazodone (TZD).

Prophylactic versus Therapeutic Fingolimod: Restoration of Presynaptic Defects in Mice Suffering from Experimental Autoimmune Encephalomyelitis.

Fingolimod, the first oral, disease-modifying therapy for MS, has been recently proposed to modulate glutamate transmission in the central nervous system (CNS) of mice suffering from Experimental Autoimmune Encephalomyelitis (EAE) and in MS patients. Our study aims at investigating whether oral fingolimod recovers presynaptic defects that occur at different stages of disease in the CNS of EAE mice. In vivo prophylactic (0.

Long-term hippocampal glutamate synapse and astrocyte dysfunctions underlying the altered phenotype induced by adolescent THC treatment in male rats.

Cannabis use has been frequently associated with sex-dependent effects on brain and behavior. We previously demonstrated that adult female rats exposed to delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term alterations in cognitive performances and emotional reactivity, whereas preliminary evidence suggests the presence of a different phenotype in male rats. To thoroughly depict the behavioral phenotype induced by adolescent THC exposure in male rats, we treated adolescent animals with increasing doses of THC twice a day (PND 35-45) and, at adulthood, we performed a battery of behavioral tests to measure affective- and psychotic-like symptoms as well as cognition.

Determinants of the half-turn with the ball in sub-elite youth soccer players.

We explored the biomechanics of the 180° change-of-direction with the ball (half-turn) in soccer. We aimed at identifying movement strategies which enhance the players' half-turning performance, by characterising technique kinematics and understanding the structure of biomechanical and anthropometrics variables. Ten Under-13 sub-elite male players were recorded with an optoelectronic motion analyser while performing a 5-m straight dribbling followed by a half-turn with the sole.

Presynaptic, release-regulating mGlu2 -preferring and mGlu3 -preferring autoreceptors in CNS: pharmacological profiles and functional roles in demyelinating disease.

Background And Purpose: Presynaptic, release-regulating metabotropic glutamate 2 and 3 (mGlu2/3) autoreceptors exist in the CNS. They represent suitable targets for therapeutic approaches to central diseases that are typified by hyperglutamatergicity. The availability of specific ligands able to differentiate between mGlu2 and mGlu3 subunits allows us to further characterize these autoreceptors.

Nicotinic modulation of glutamate receptor function at nerve terminal level: a fine-tuning of synaptic signals.

This review focuses on a specific interaction occurring between the nicotinic cholinergic receptors (nAChRs) and the glutamatergic receptors (GluRs) at the nerve endings level. We have employed synaptosomes in superfusion and supplemented and integrated our findings with data obtained using techniques from molecular biology and immuno-cytochemistry, and the assessment of receptor trafficking. In particular, we characterize the following: (1) the direct and unequivocal localization of native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamatergic receptors on specific nerve terminals, (2) their pharmacological characterization and functional co-localization with nAChRs on the same nerve endings, and (3) the existence of synergistic or antagonistic interactions among them.

Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate release.

Activation of c-Jun N-terminal kinase (JNK) signaling pathway is a critical step for neuronal death occurring in several neurological conditions. JNKs can be activated via receptor tyrosine kinases, cytokine receptors, G-protein coupled receptors and ligand-gated ion channels, including the NMDA glutamate receptors. While JNK has been generally associated with postsynaptic NMDA receptors, its presynaptic role remains largely unexplored.