Neuroscience
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Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disorder of the central nervous system (CNS) targeting myelinated axons. Pathogenesis of MS entails an intricate genetic, environmental, and immunological interaction. Dysregulation of immune response i.e. autoreactive T & B-Cells and macrophage infiltration into the CNS leads to inflammation, demyelination, and neurodegeneration. ⋯ Therapeutic innovations have significantly transformed the management of MS, especially the use of disease-modifying therapies (DMTs) to reduce relapse rates and control disease progression. Advancements in research, neuroprotective strategies, and remyelination strategies hold promising results in reversing CNS damage. Various mice models are being adopted for testing new entities in MS research.
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The brain of patients with Parkinson's disease (PD) was characterized by increased phosphorylation and oligomerization of α-synuclein (α-syn) and altered activity of enzymes regulating α-syn phosphorylation and oligomerization. Whether increased α-syn phosphorylation and oligomerization as well as related enzyme changes can be detected in the plasma of PD patients remains unclear. ⋯ Moreover, they were both positively correlated with Hoehn and Yahr staging and polo-like kinase 2 (PLK2, an enzyme promoting α-syn phosphorylation) levels, and negatively correlated with protein phosphatase 2A levels (PP2A, an enzyme dephosphorylating α-syn) and glucocerebrosidase (GCase, an enzyme whose deficiency causes α-syn oligomerization) activity and ceramide (a product of GCase and a natural PP2A activator) levels. The above results suggest that increased α-syn oligomerization and phosphorylation rates and related enzyme changes can be detected in PD plasma and used to discriminate PD patients from HC subjects and predict PD progression.
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In two recent papers (Curr Trends Neurol 17: 83-98, 2023; J Neurophysiol 124: 1029-1044, 2020), James Lee has argued that his Transmembrane Electrostatically-Localized Cations (TELC) hypothesis offers a model of neuron transmembrane potentials that is superior to Hodgkin-Huxley classic cable theory and the Goldman-Hodgkin-Katz (GHK) equation. Here we examine critically the arguments in these papers, finding key weaknesses and fallacies. We also examine closely the literature cited by Lee, and find (i) strong support for the GHK equation; (ii) published measurements that contradict TELC predictions; and (iii) no convincing support for the TELC hypothesis.
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Peripuberty is a significant period of neurodevelopment with long-lasting effects on the brain and behavior. Blocking type 1 corticotropin-releasing factor receptors (CRFR1) in neonatal and peripubertal rats attenuates detrimental effects of early-life stress on neural plasticity, behavior, and stress hormone action, long after exposure to the drug has ended. CRFR1 antagonism can also impact neural and behavioral development in the absence of stressful stimuli, suggesting sustained alterations under baseline conditions. ⋯ In the adult amygdala, peripubertal CRFR1a induced alterations in pathways related to neural plasticity and stress in males. In females, pathways related to central nervous system myelination, cell junction organization, and glutamatergic regulation of synaptic transmission were affected. Understanding how acute exposure to neuropharmacological agents can have sustained impacts on brain and behavior, in the absence of further exposures, has important clinical implications for developing adolescents.
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Widespread white matter (WM) microstructural abnormalities have been reported in patients with spinocerebellar ataxia type 3 (SCA3) using diffusion tensor imaging (DTI), whereas the ability of DTI to detect WM degeneration over short-term period remains insufficiently explored. Additionally, WM dysfunction remains entirely unknown in this disease. This study aims to investigate WM structural and functional alterations in SCA3, and provide promising progression biomarkers for short-term clinical trials. ⋯ The longitudinal analysis further showed decreased ALFF in the right PLIC and increased mean diffusivity in the left inferior cerebellar peduncle and right medial lemniscus over time in SCA3 patients. These findings emphasized that pons and the CST were the most vulnerable WM areas in SCA3, and have the potential to become therapeutic targets of SCA3 for upcoming interventional trials. In addition, both DT metrics and WM ALFF were efficient progression biomarkers for SCA3 even in short-term period.