Research

Neuronal activity can be modulated by transmitters that act through receptors coupled to heterotrimeric G proteins. Activation of these G protein signal transdu...

l-DOPA-induced dyskinesia (LID) is a debilitating motor side effect arising from chronic dopamine (DA) replacement therapy with l-DOPA for the treatment of Parkinson’s disease. LID is associated with supersensitivity of striatal dopaminergic signaling and fluctuations in synaptic DA following each l-DOPA dose, shrinking the therapeutic window. The heterogeneous composition of the striatum, including subpopulations of medium spiny output neurons (MSNs), interneurons, and supporting cells, complicates the identification of cell(s) underlying LID. We used single-nucleus RNA sequencing (snRNA-seq) to establish a comprehensive striatal transcriptional profile during LID development. Male hemiparkinsonian mice were treated with vehicle or l-DOPA for 1, 5, or 10 d, and striatal nuclei were processed for snRNA-seq. Analyses indicated a limited population of DA D1 receptor–expressing MSNs (D1-MSNs) formed three subclusters in response to l-DOPA treatment and expressed cellular markers of activation. These activated D1-MSNs display similar transcriptional changes previously associated with LID; however, their prevalence and transcriptional behavior were differentially influenced by l-DOPA experience. Differentially expressed genes indicated acute upregulation of plasticity-related transcription factors and mitogen-activated protein kinase signaling, while repeated l-DOPA-induced synaptic remodeling, learning and memory, and transforming growth factor-β (TGF-β) signaling genes. Notably, repeated l-DOPA sensitized Inhba , an activin subunit of the TGF-β superfamily, in activated D1-MSNs, and its pharmacological inhibition impaired LID development, suggesting that activin signaling may play an essential role in LID. These data suggest distinct subsets of D1-MSNs become differentially l-DOPA-responsive due to aberrant induction of molecular mechanisms necessary for neuronal entrainment, similar to processes underlying hippocampal learning and memory.

In order to reduce the reoccurrence of another pandemic spike, Contactless Pathways in the workplace are being developed using contactless technology to significantly reduce person-to-person contact.

Every cell within our body holds information in the form of energy. This energy contains the memories of all our life experiences as well as ancestral memory and the essence of our soul.

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I return to the spirit of the first ezine I released in 2016 which focused on the power of words. Important then and important now. Word. A simple f-o-u-r letter word that can carry pleasure

The discharge to assess pathway is something we launched at Active Pathways 5 years ago with incredible success...

Key Points. Contact/intrinsic and extrinsic pathways of coagulation are both activated in COVID-19 and likely contribute to FIX activation in vivo.FIXa:AT

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The Mathematical Modelling of Natural Phenomena (MMNP) is an international research journal, which publishes top-level original and review papers, short communications and proceedings on mathematical modelling in biology, medicine, chemistry, physics, and other areas.

The AOP is an innovative model for those experiencing severe multiple-disadvantage, specifically aimed at helping the most vulnerable in our community to move on.

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