Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson's Disease.

Treatment with L-3,4-dihydroxyphenylalanine (L-Dopa) compensates for decreased striatal dopamine (DA) levels and reduces Parkinson's disease (PD) symptoms. However, during disease progression, L-Dopa-induced dyskinesia (LID) develops virtually in all PD patients, making the control of PD symptoms difficult. Thus, understanding the mechanisms underlying LID and the control of these motor abnormalities is a major issue in the care of PD patients.

Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson's disease restoring striatal synaptic plasticity.

Intensive physical activity improves motor functions in patients with Parkinson's disease (PD) at early stages. However, the mechanisms underlying the beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested the hypothesis that an intensive treadmill training program rescues alterations in striatal plasticity and early motor and cognitive deficits in rats receiving an intrastriatal injection of alpha-synuclein (α-syn) preformed fibrils.

Advances in understanding the function of alpha-synuclein: implications for Parkinson's disease.

The critical role of alpha-synuclein in Parkinson's disease represents a pivotal discovery. Some progress has been made over recent years in identifying disease-modifying therapies for Parkinson's disease that target alpha-synuclein. However, these treatments have not yet shown clear efficacy in slowing the progression of this disease.

A positive allosteric modulator of mGlu4 receptors restores striatal plasticity in an animal model of l-Dopa-induced dyskinesia.

By decreasing glutamate transmission, mGlu4 receptor positive allosteric modulators (mGlu4-PAM), in combination with levodopa (l-DOPA) may restore the synergy between glutamatergic and dopaminergic transmissions, thus maximizing the improvement of motor function in Parkinson's disease (PD). This study aimed to clarify the effects of foliglurax, a selective mGlu4-PAM, on the loss of bidirectional synaptic plasticity associated with l-DOPA-induced dyskinesia (LID). Behavioral assessments compared dyskinesia intensity in 6-hydroxydopamine (6-OHDA)-lesioned rats treated with l-DOPA or l-DOPA plus foliglurax.

Alpha-synuclein and cortico-striatal plasticity in animal models of Parkinson disease.

Alpha-synuclein (α-synuclein) is a small, acidic protein containing 140 amino acids, highly expressed in the brain and primarily localized in the presynaptic terminals. It is found in high concentrations in Lewy Bodies, proteinaceous aggregates that constitute a typical histopathologic hallmark of Parkinson's disease. Altered environmental conditions, genetic mutations and post-translational changes can trigger abnormal aggregation processes with the increased frequency of oligomers, protofibrils, and fibrils formation that perturbs the neuronal homeostasis leading to cell death.

Cost-Effective Method to Perform SARS-CoV-2 Variant Surveillance: Detection of Alpha, Gamma, Lambda, Delta, Epsilon, and Zeta in Argentina.

SARS-CoV-2 variants with concerning characteristics have emerged since the end of 2020. Surveillance of SARS-CoV-2 variants was performed on a total of 4,851 samples from the capital city and 10 provinces of Argentina, during 51 epidemiological weeks (EWs) that covered the end of the first wave and the ongoing second wave of the COVID-19 pandemic in the country (EW 44/2020 to EW 41/2021). The surveillance strategy was mainly based on Sanger sequencing of a Spike coding region that allows the identification of signature mutations associated with variants.

Effects of uremic toxins on hippocampal synaptic transmission: implication for neurodegeneration in chronic kidney disease.

Patients affected by chronic kidney disease (CKD) have an increased risk of developing cognitive impairment. The cause of mental health disorders in CKD and in chronic hemodialysis patients is multifactorial, due to the interaction of classical cardiovascular disease risk factors, kidney- and dialysis-related risk factors with depression, and multiple drugs overuse. A large number of compounds, defined as uremic toxins that normally are excreted by healthy kidneys, accumulate in the circulations, in the tissues, and in the organs of CKD patients.

Transcranial Magnetic Stimulation Exerts "Rejuvenation" Effects on Corticostriatal Synapses after Partial Dopamine Depletion.

Background: In experimental models of Parkinson's disease (PD), different degrees of degeneration to the nigrostriatal pathway produce distinct profiles of synaptic alterations that depend on progressive changes in N-methyl-D-aspartate receptors (NMDAR)-mediated functions. Repetitive transcranial magnetic stimulation (rTMS) induces modifications in glutamatergic and dopaminergic systems, suggesting that it may have an impact on glutamatergic synapses modulated by dopamine neurotransmission. However, no studies have so far explored the mechanisms of rTMS effects at early stages of PD.

Serotonin drives striatal synaptic plasticity in a sex-related manner.

Introduction: Plasticity at corticostriatal synapses is a key substrate for a variety of brain functions - including motor control, learning and reward processing - and is often disrupted in disease conditions. Despite intense research pointing toward a dynamic interplay between glutamate, dopamine (DA), and serotonin (5-HT) neurotransmission, their precise circuit and synaptic mechanisms regulating their role in striatal plasticity are still unclear. Here, we analyze the role of serotonergic raphe-striatal innervation in the regulation of DA-dependent corticostriatal plasticity.

Long-Term Shaping of Corticostriatal Synaptic Activity by Acute Fasting.

Food restriction is a robust nongenic, nonsurgical and nonpharmacologic intervention known to improve health and extend lifespan in various species. Food is considered the most essential and frequently consumed natural reward, and current observations have demonstrated homeostatic responses and neuroadaptations to sustained intermittent or chronic deprivation. Results obtained to date indicate that food deprivation affects glutamatergic synapses, favoring the insertion of GluA2-lacking α-Ammino-3-idrossi-5-Metil-4-idrossazol-Propionic Acid receptors (AMPARs) in postsynaptic membranes.

Rapamycin, by Inhibiting mTORC1 Signaling, Prevents the Loss of Striatal Bidirectional Synaptic Plasticity in a Rat Model of L-DOPA-Induced Dyskinesia.

Levodopa (L-DOPA) treatment is the main gold-standard therapy for Parkinson disease (PD). Besides good antiparkinsonian effects, prolonged use of this drug is associated to the development of involuntary movements known as L-DOPA-induced dyskinesia (LID). L-DOPA-induced dyskinesia is linked to a sensitization of dopamine (DA) D1 receptors located on spiny projection neurons (SPNs) of the dorsal striatum.

Author Correction: Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson's disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Corticostriatal synaptic plasticity alterations in the R6/1 transgenic mouse model of Huntington's disease.

Huntington's disease (HD) is a genetic neurodegenerative condition characterized by abnormal dopamine (DA)-glutamate interactions, severe alterations in motor control, and reduced behavioral flexibility. Experimental models of disease show that during symptomatic phases, HD shares with other hyperkinetic disorders the loss of synaptic depotentiation in the striatal spiny projection neurons (SPNs). Here we test the hypothesis that corticostriatal long-term depression (LTD), a well-conserved synaptic scaling down response to environmental stimuli, is also altered in symptomatic male R6/1 mice, a HD model with gradual development of symptoms.

Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson's disease.

Neuroinflammation is one of the hallmarks of Parkinson's disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure to resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, the effects of stimulating the resolution of inflammation in PD - to modulate disease progression - still remain unexplored.

Dopamine drives binge-like consumption of a palatable food in experimental Parkinsonism.

Background: Prolonged dopaminergic replacement therapy in PD results in pulsatile dopamine receptors stimulation in both dorsal and ventral striatum causing wearing off, motor fluctuations, and nonmotor side effects such as behavioral addictions. Among impulse control disorders, binge eating can be easily modeled in laboratory animals.

Objectives: We hypothesize that manipulation of dopamine levels in a 6-hydroxydopamine-lesioned rats, as a model of PD characterized by a different extent of dopamine denervation between dorsal and ventral striatum, would influence both synaptic plasticity of the nucleus accumbens and binge-like eating behavior.

NMDA receptor GluN2D subunit participates to levodopa-induced dyskinesia pathophysiology.

In the striatum, specific N-methyl-d-aspartate receptor (NMDAR) subtypes are found in different neuronal cells. Spiny projection neurons (SPNs) are characterized by NMDARs expressing GluN2A and GluN2B subunits, while GluN2D is exclusively detected in striatal cholinergic interneurons (ChIs). In Parkinson's disease (PD), dopamine depletion and prolonged treatment with levodopa (L-DOPA) trigger adaptive changes in the glutamatergic transmission from the cortex to the striatum, also resulting in the aberrant function of striatal NMDARs.

An evaluation of the dot-ELISA procedure as a diagnostic test in an area with a high prevalence of human Toxocara canis infection.

The aim of this work was to evaluate a dot-enzyme-linked immunosorbent assay (dot-ELISA) using excretory-secretory antigens from the larval stages of Toxocara canis for the diagnosis of toxocariasis. A secondary aim was to establish the optimal conditions for its use in an area with a high prevalence of human T. canis infection.