Neuropathology in an α-synuclein preformed fibril mouse model occurs independent of the Parkinson's disease-linked lysosomal ATP13A2 protein.

Loss-of-function mutations in the ATP13A2 (PARK9) gene are implicated in early-onset autosomal recessive Parkinson's disease (PD) and other neurodegenerative disorders. ATP13A2 encodes a lysosomal transmembrane P-type ATPase that is highly expressed in brain and specifically within the substantia nigra pars compacta (SNc). Recent studies have revealed its normal role as a lysosomal polyamine transporter, although its contribution to PD-related pathology remains unclear.

Corrigendum: Striatal dopamine D2-muscarinic acetylcholine M1 receptor-receptor interaction in a model of movement disorders.

[This corrects the article DOI: 10.3389/fphar.2020.

Functional interplay between adenosine A receptor and NMDA preconditioning in fear memory and glutamate uptake in the mice hippocampus.

N-methyl D-aspartate (NMDA) administered at subtoxic dose plays a protective role against neuronal excitotoxicity, a mechanism described as preconditioning. Since the activation of adenosinergic receptors influences the achievement of NMDA preconditioning in the hippocampus, we evaluated the potential functional interplay between adenosine A and A receptors (AR and AR) activities and NMDA preconditioning. Adult male Swiss mice received saline (NaCl 0.

Striatal Dopamine D-Muscarinic Acetylcholine M Receptor-Receptor Interaction in a Model of Movement Disorders.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor control deficits, which is associated with the loss of striatal dopaminergic neurons from the substantia nigra. In parallel to dopaminergic denervation, there is an increase of acetylcholine within the striatum, resulting in a striatal dopaminergic-cholinergic neurotransmission imbalance. Currently, available PD pharmacotherapy (e.

Adenosine A-A Receptor-Receptor Interaction: Contribution to Guanosine-Mediated Effects.

Guanosine, a guanine-based purine nucleoside, has been described as a neuromodulator that exerts neuroprotective effects in animal and cellular ischemia models. However, guanosine's exact mechanism of action and molecular targets have not yet been identified. Here, we aimed to elucidate a role of adenosine receptors (ARs) in mediating guanosine effects.

Guanosine Protects Striatal Slices Against 6-OHDA-Induced Oxidative Damage, Mitochondrial Dysfunction, and ATP Depletion.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra pars compacta which induces severe motor symptoms. 6-OHDA is a neurotoxin widely used in PD animal models due to its high affinity by dopamine transporter, its rapid non-enzymatic auto-oxidation which generates reactive oxygen species (ROS), oxidative stress, and for induced mitochondrial dysfunction. We previously reported an in vitro protocol of 6-OHDA-induced toxicity in brain regions slices, as a simple and sensitive assay to screen for protective compounds related to PD.

Intranasal administration of sodium dimethyldithiocarbamate induces motor deficits and dopaminergic dysfunction in mice.

The primary etiology of Parkinson's disease (PD) remains unclear, but likely reflects a combination of genetic and environmental factors. Exposure to some pesticides, including ziram (zinc dimethyldithiocarbamate), is a relevant risk factor for PD. Like some other environmental neurotoxicants, we hypothesized that ziram can enter the central nervous system from the nasal mucosa via the olfactory nerves.

Antiparkinsonian Efficacy of Guanosine in Rodent Models of Movement Disorder.

Guanosine (GUO) is a guanine-based purine nucleoside with important trophic functions and promising neuroprotective properties. Although the neuroprotective effects of GUO have been corroborated in cellular models of Parkinson's disease (PD), its efficacy as an antiparkinsonian agent has not been fully explored in PD animal models. Accordingly, we evaluated the effectiveness of GUO in reversing motor impairments in several rodent movement disorder models, including catalepsy, tremor, and hemiparkinsonism.

In vitro 6-hydroxydopamine-induced toxicity in striatal, cerebrocortical and hippocampal slices is attenuated by atorvastatin and MK-801.

Parkinson's disease (PD) involves the loss of striatal dopaminergic neurons, although other neurotransmitters and brain areas are also involved in its pathophysiology. In rodent models to PD it has been shown statins improve cognitive and motor deficits and attenuate inflammatory responses evoked by PD-related toxins. Statins are the drugs most prescribed to hypercholesterolemia, but neuroprotective effects have also been attributed to statins treatment in humans and in animal models.

Atorvastatin Protects from Aβ-Induced Cell Damage and Depressive-Like Behavior via ProBDNF Cleavage.

Intracerebroventricular (icv) amyloid-beta (Aβ) infusion to mice has been demonstrated to cause neurotoxicty and depressive-like behavior and it can be used to evaluate antidepressant and neuroprotective effect of drugs. Atorvastatin is a widely used statin that has demonstrated antidepressant-like effect in predictable animal behavioral models and neuroprotective effect against Aβ infusion. The purpose of this study was to determine the effect of in vivo atorvastatin treatment against Aβ-induced changes in mood-related behaviors and biochemical parameters in ex vivo hippocampal slices from mice.