Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents.

Prosaposin (PSAP) modulates glycosphingolipid metabolism and variants have been linked to Parkinson's disease (PD). Here, we find altered PSAP levels in the plasma, CSF and post-mortem brain of PD patients. Altered plasma and CSF PSAP levels correlate with PD-related motor impairments.

Age- and Sex-Dependent Behavioral and Neurochemical Alterations in hLRRK2-G2019S BAC Mice.

The G2019S mutation in the leucine-rich repeat kinase 2 () gene is associated with late-onset Parkinson's disease (PD). Although PD affects men and women differently, longitudinal studies examining sex- and age-dependent alterations in mice carrying the G2019S mutation are limited. We examined if behavioral and neurochemical dysfunctions, as well as neurodegeneration, occur in male and female BAC LRRK2-hG2019S (G2019S) mice, compared to their age-matched wild type littermates, at four age ranges.

Neuronal Firing and Glutamatergic Synapses in the Substantia Nigra Pars Reticulata of LRRK2-G2019S Mice.

Pathogenic mutations in the leucine-rich repeat kinase 2 () gene are frequent causes of familial Parkinson's Disease (PD), an increasingly prevalent neurodegenerative disease that affects basal ganglia circuitry. The cellular effects of the G2019S mutation in the gene, the most common pathological mutation, have not been thoroughly investigated. In this study we used middle-aged mice carrying the LRRK2-G2019S mutation (G2019S mice) to identify potential alterations in the neurophysiological properties and characteristics of glutamatergic synaptic transmission in basal ganglia output neurons, i.

The impacts of total quality management practices in Algerian higher education institutions.

Algerian universities rely on total quality management. TQM is one of the most successful strategic options for improving the quality of higher education. In addition, achieving academic accreditation and progress in international rankings.

PRC2-mediated repression is essential to maintain identity and function of differentiated dopaminergic and serotonergic neurons.

How neurons can maintain cellular identity over an entire life span remains largely unknown. Here, we show that maintenance of identity in differentiated dopaminergic and serotonergic neurons is critically reliant on the Polycomb repressive complex 2 (PRC2). Deletion of the obligate PRC2 component, , in these neurons resulted in global loss of H3K27me3, followed by a gradual activation of genes harboring both H3K27me3 and H3K9me3 modifications.

The Impact of e-Learning Systems on Motivating Students and Enhancing Their Outcomes During COVID-19: A Mixed-Method Approach.

e-Learning is a key strategy in the course of higher education to improve the results of the educational process and stimulate student motivation. The COVID-19 pandemic imposed on Algerian universities to adopt e-Learning systems to search for effectiveness and efficiency of academic approaches. This paper seeks to remedy these problems by analyzing the impact of e-Learning systems on student motivation and outcomes.

Exploring the Relationship Between Organizational Culture Types and Knowledge Management Processes: A Meta-Analytic Path Analysis.

This study investigated the relationship between organizational culture types according to Competing Values Framework (Clan, Adhocracy, Market, Hierarchy) and Knowledge Management Processes (Creation, Dissemination, Storage, Application) using meta-analytic path analysis. To produce the necessary pooled correlation matrix for model testing, we used the univariate (r) approach to carry out two additional meta-analyzes. Based on data collected from several research databases, we extracted the paired correlation coefficients (r) among knowledge management processes ( = 32, = 6835) then the inter-correlations between knowledge management processes and culture types ( = 7, = 865).

E-Learning Research Trends in Higher Education in Light of COVID-19: A Bibliometric Analysis.

This paper provides a broad bibliometric overview of the important conceptual advances that have been published during COVID-19 within "e-learning in higher education." E-learning as a concept has been widely used in the academic and professional communities and has been approved as an educational approach during COVID-19. This article starts with a literature review of e-learning.

LRRK2-G2019S mice display alterations in glutamatergic synaptic transmission in midbrain dopamine neurons.

The progressive degeneration of dopamine (DA) neurons in the substantia nigra compacta (SNc) leads to the emergence of motor symptoms in patients with Parkinson's disease (PD). To propose neuroprotective therapies able to slow or halt the progression of the disease, it is necessary to identify cellular alterations that occur before DA neurons degenerate and before the onset of the motor symptoms that characterize PD. Using electrophysiological, histochemical, and biochemical approaches, we have examined if glutamatergic synaptic transmission in DA neurons in the SNc and in the adjacent ventral tegmental area (VTA) was altered in middle-aged (10-12 months old) mice with the hG2019S point mutation (G2019S) in the leucine-rich repeat kinase 2 (LRRK2) gene.

Ketamine induces opposite changes in AMPA receptor calcium permeability in the ventral tegmental area and nucleus accumbens.

Ketamine elicits rapid and durable antidepressant actions in treatment-resistant patients with mood disorders such as major depressive disorder and bipolar depression. The mechanisms might involve the induction of metaplasticity in brain regions associated with reward-related behaviors, mood, and hedonic drive, particularly the ventral tegmental area (VTA) and the nucleus accumbens (NAc). We have examined if ketamine alters the insertion of the GluA2 subunit of AMPA receptors (AMPAR), which determines calcium permeability of the channel, at glutamatergic synapses onto dopamine (DA) neurons in the VTA and spiny projection neurons (SPNs) in the Core region of the NAc.

Key Sectors in the Economy of Saudi Arabia.

This study shows the key sector for the economy of Saudi Arabia based on input-output model analyses. They derived the analyses from the economy of the Kingdom of Saudi Arabia (KSA) using 35 economic sectors. We found that four leading sectors exceeded the values of the linkage coefficients with a value of 1, represented by both chemicals and pharmaceutical products, namely, manufacturing basic metals (S13), transportation and storage (S24), and other business sector services (S31).

COVID-19 Deaths Cases Impact on Oil Prices: Probable Scenarios on Saudi Arabia Economy.

The purpose of this paper is to discuss death cases on the World, exacerbated investor fears, uncertainties, and increased volatility of crude oil prices in financial markets. The reaction absorbed the epidemic gradually until January 22. Still, the market situation changed soon with a sharp drop in prices, and prices slowly recovered after that until June 14.

NMDA receptors are altered in the substantia nigra pars reticulata and their blockade ameliorates motor deficits in experimental parkinsonism.

In Parkinson's disease (PD) reduced levels of dopamine (DA) in the striatum lead to an abnormal circuit activity of the basal ganglia and an increased output through the substantia nigra pars reticulata (SNr) and the globus pallidus internal part. Synaptic inputs to the SNr shape its activity, however, the properties of glutamatergic synaptic transmission in this output nucleus of the basal ganglia in control and DA-depleted conditions are not fully elucidated. Using whole-cell patch-clamp recordings and pharmacological tools, we examined alterations in glutamatergic synaptic transmission in the SNr of a mouse model of PD, i.

Deficits in Motor Performance, Neurotransmitters and Synaptic Plasticity in Elderly and Experimental Parkinsonian Mice Lacking GPR37.

Parkinson's disease (PD) etiology is attributed to aging and the progressive neurodegeneration of dopamine (DA) neurons of substantia nigra pars compacta (SNc). GPR37 is an orphan G-protein Coupled Receptor (GPCR) that is linked to the juvenile form of PD. In addition, misfolded GPR37 has been found in Lewy bodies.

Striatal Tyrosine Hydroxylase Is Stimulated via TAAR1 by 3-Iodothyronamine, But Not by Tyramine or β-Phenylethylamine.

The trace amine-associated receptor 1 (TAAR1) is expressed by dopaminergic neurons, but the precise influence of trace amines upon their functional activity remains to be fully characterized. Here, we examined the regulation of tyrosine hydroxylase (TH) by tyramine and beta-phenylethylamine (β-PEA) compared to 3-iodothyronamine (TAM). Immunoblotting and amperometry were performed in dorsal striatal slices from wild-type (WT) and TAAR1 knockout (KO) mice.

High frequency stimulation induces LTD of AMPA receptor-mediated postsynaptic responses and LTP of synaptically-evoked firing in the dorsolateral striatum.

In the striatum, long term potentiation (LTP) and long-term depression (LTD) of glutamatergic transmission are believed to underlie motor learning and are impaired in animal models of Parkinson's disease. High frequency stimulation (HFS) is often used to induce synaptic plasticity in the brain. In the striatum, the polarity of HFS-induced plasticity is influenced by the recording conditions, which can differ between various studies.

CIQ, a positive allosteric modulator of GluN2C/D-containing N-methyl-d-aspartate receptors, rescues striatal synaptic plasticity deficit in a mouse model of Parkinson's disease.

Aims: To investigate if CIQ, a positive allosteric modulator of N-methyl-d-aspartate receptors (NMDARs) containing GluN2C/D subunits, rescues the loss of long-term potentiation (LTP) and forelimb-use asymmetry in a mouse model of Parkinson's disease (PD).

Methods: We have used electrophysiology in brain slices and the cylinder test to examine the effect of CIQ on glutamatergic synaptic transmission, synaptic plasticity, and forelimb-use in the unilateral 6-hydroxydopamine-lesion mouse model of PD.

Results: CIQ, applied in the perfusion solution, reversibly reduced glutamatergic synaptic transmission in the dopamine-depleted striatum and had no effect in the dopamine-intact striatum.

Ketamine and its metabolite (2R,6R)-hydroxynorketamine induce lasting alterations in glutamatergic synaptic plasticity in the mesolimbic circuit.

Low doses of ketamine trigger rapid and lasting antidepressant effects after one injection in treatment-resistant patients with major depressive disorder. Modulation of AMPA receptors (AMPARs) in the hippocampus and prefrontal cortex is suggested to mediate the antidepressant action of ketamine and of one of its metabolites (2R,6R)-hydroxynorketamine ((2R,6R)-HNK). We have examined whether ketamine and (2R,6R)-HNK affect glutamatergic transmission and plasticity in the mesolimbic system, brain regions known to have key roles in reward-motivated behaviors, mood and hedonic drive.

The GABAA receptor agonist muscimol induces an age- and region-dependent form of long-term depression in the mouse striatum.

Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABAA receptor agonist muscimol was recently found to trigger a long-lasting depression of glutamatergic synaptic transmission in the NAc of adolescent mice, but the mechanisms that underlie this novel form of LTD were not studied.

Dopamine depletion of the striatum causes a cell-type specific reorganization of GluN2B- and GluN2D-containing NMDA receptors.

The GluN2B subunit of NMDA receptors (NMDARs) is an attractive drug target for therapeutic intervention in Parkinson's disease (PD). We have used whole-cell patch clamp recordings in brain slices to examine the contribution of GluN2B and GluN2D to functional NMDARs in the striatum of the unilateral 6-hydroxydopamine-lesioned mouse model of PD. We found that current/voltage relationships of NMDAR-mediated excitatory post synaptic currents were altered in a population of medium spiny projection neurons (MSNs) in the dopamine-depleted striatum.

Induction of cannabinoid- and N-methyl-D-aspartate receptor-mediated long-term depression in the nucleus accumbens and dorsolateral striatum is region and age dependent.

Background: The adolescent brain is sensitive to experience-dependent plasticity and might be more vulnerable than the adult brain to the effects of some drugs of abuse. The factors that contribute to these differences are not fully identified. We have examined the ability of cannabinoids to induce a form of synaptic plasticity, long-term depression, in the nucleus accumbens and dorsolateral striatum of adolescent and adult mice.

Difficult peripheral venous access: clinical evaluation of a catheter inserted with the Seldinger method under ultrasound guidance.

Purpose: A preliminary observational study was undertaken to evaluate the risk of failure of ultrasound-guided peripheral intravenous catheterization of a deep arm vein for a maximum of 7 days, after peripheral intravenous (PIV) cannulation failure.

Methods: This prospective study included patients referred to the intensive care unit for placement of a central line, a polyurethane cannula commercialized for arterial catheterization was used for peripheral venous cannulation. Catheter length and diameter were chosen based on preliminary ultrasound measurements of vein diameter and skin-vein distance.