Over-expression of Dyrk1A affects bleeding by modulating plasma fibronectin and fibrinogen level in mice.

Down syndrome is the most common chromosomal abnormality in humans. Patients with Down syndrome have hematologic disorders, including mild to moderate thrombocytopenia. In case of Down syndrome, thrombocytopenia is not associated with bleeding, and it remains poorly characterized regarding molecular mechanisms. We investigated the effects of overexpression of Dyrk1A, an important factor contributing to some major Down syndrome phenotypes, on platelet number and bleeding in mice. Mice overexpressing Dyrk1A have a decrease in platelet number by 20%. However, bleeding time was found to be reduced by 50%. The thrombocytopenia and the decreased bleeding time observed were not associated to an abnormal platelet receptors expression, to a defect of platelet activation by ADP, thrombin or convulxin, to the presence of activated platelets in the circulation or to an abnormal half-life of the platelets. To propose molecular mechanisms explaining this discrepancy, we performed a network analysis of Dyrk1A interactome and demonstrated that Dyrk1A, fibronectin and fibrinogen interact indirectly through two distinct clusters of proteins. Moreover, in mice overexpressing Dyrk1A, increased plasma fibronectin and fibrinogen levels were found, linked to an increase of the hepatic fibrinogen production. Our results indicate that overexpression of Dyrk1A in mice induces decreased bleeding consistent with increased plasma fibronectin and fibrinogen levels, revealing a new role of Dyrk1A depending on its indirect interaction with these two proteins.

Repurposing GLP-1 Receptor Agonists for Parkinson's Disease: Current Evidence and Future Opportunities.

The global burden of chronic disorders such as Parkinson's disease (PD) has rapidly increased over recent decades. Despite an increasing understanding of PD pathophysiology, there are no effective therapies capable of stopping or slowing the progression of this neurological condition. It has been suggested that type 2 diabetes mellitus (T2DM) may be a risk factor for PD and comorbid T2DM may worsen PD symptoms, as well as accelerate neurodegeneration. In fact, the similar pathological mechanisms shared by PD and T2DM have inspired several studies on the therapeutic potential of T2DM drugs against PD, among which glucagon-like peptide-1 receptor (GLP-1R) agonists are promising candidates. Here, we highlight the mechanisms linking T2DM and PD, as well as the links between insulin resistance (IR) and PD patients' risk of developing cognitive deficits. We also briefly review the effects of GLP-1R agonists on PD and discuss how the successful use of these substances in preclinical models of PD has paved the way for PD clinical trials. We further discuss how recent evidence on the beneficial effects of dulaglutide on cognitive function of T2DM patients may have important implications for PD drug repurposing.

Effects of fish oil supplementation on spatial memory in rats with pilocarpine-induced epilepsy assessed using the Morris Water Maze test.

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) are at high risk of experiencing cognitive impairment. Such dysfunction is also observed in an animal model of TLE, the rat model of pilocarpine-induced epilepsy. METHODS: We investigated the effects of fish oil supplementation on spatial memory in rats with pilocarpine-induced epilepsy using the Morris Water Maze (MWM) test. RESULTS: Although rats with pilocarpine-induced epilepsy treated with fish oil learned the platform location significantly faster by Day 7 of the acquisition phase, spatial memory performance of these rats was unaffected by fish oil supplementation during probe trials. SIGNIFICANCE: Our study provides insights into the importance of considering nutraceutical strategies for enhancing cognitive abilities in patients with TLE.

COVID-19 and stroke: Red flags for secondary movement disorders?

•Hypercoagulability may predispose COVID-19 patients to thromboembolic complications.•Movement disorders may develop as complications of vascular events and infections.•Health professionals should be vigilant for abnormal movements in COVID-19 patients.

Endogenous protection against the 6-OHDA model of Parkinson's disease in the Amazonian rodent Proechimys.

BACKGROUND: Proechimys, an epilepsy-resistant rodent from Amazon Rainforest, is a promising alternative animal model for studying neurodegenerative disorders. OBJECTIVES: To evaluate behavioral and immunohistological changes in Proechimys after 6-OHDA-induced model of PD. METHODS: Following unilateral injections of 6-OHDA into striatum, animals were assessed for exploratory behavior using the cylinder test. Brain sections were submitted to immunohistochemistry for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1). RESULTS: We observed normal exploratory behavior during cylinder test in all animals. We could not detect changes in the expression of TH in both striatum and SNc, suggesting that Proechimys is resistant to dopaminergic neuronal degeneration. Glial activation was observed by an increase in Iba-1 expression in both striatum and SNc, and by an increase in GFAP expression in striatum. CONCLUSIONS: Proechimys represents a promising animal model for studying the mechanisms underlying the susceptibility of dopaminergic neurons to degeneration induced by 6-OHDA.