Neuroscience
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Local protein synthesis (LPS) in axons is now recognized as a physiological process, participating both in the maintenance of axonal function and diverse plastic phenomena. In the last decades of the 20th century, the existence and function of axonal LPS were topics of significant debate. Very early, axonal LPS was thought not to occur at all and was later accepted to play roles only during development or in response to specific conditions. ⋯ This review discusses key findings related to the localization and abundance of axonal mRNAs and their translation levels, both in basal states and in response to physiological processes, such as learning and memory consolidation, as well as neurodevelopmental and neurodegenerative disorders, including Alzheimer's disease, autism spectrum disorder, and axonal injury. Moreover, we discuss the current understanding of axonal ribosomes, from their localization to the potential roles of locally translated ribosomal proteins, in the context of emerging research that highlights the regulatory roles of the ribosome in translation. Lastly, we address the main challenges and open questions for future studies.
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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.
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Down syndrome (DS), caused by trisomy 21, is characterized by intellectual disability and accelerated aging, with chronic oxidative stress contributing to neurological deficits. REST (Repressor Element-1 Silencing Transcription factor), a crucial regulator of neuronal gene expression implicated in DS neuropathology. This study investigates the neuroprotective potential of lithium, a mood stabilizer with known cognitive-enhancing effects, in restoring levels of REST. ⋯ The lithium treatment also significantly reduced ROS levels in the stressed control neurons. These findings reveal a positive association between lithium treatment, REST restoration, and oxidative stress reduction, suggesting that repurposing lithium could contribute to developing therapeutic strategies for DS neuropathologies. This study provides novel insights into DS molecular mechanisms and highlights the potential of lithium as a targeted intervention for improving neuronal function in DS.
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The experiment was designed to explore the effects and mechanism of Dilong on alleviating cyclophosphamide (CTX)-induced brain injury in mice. Fifty male SPF Kunming mice aged 6-8 weeks were randomly divided into five groups: Group A served as the control group; Group B received intraperitoneal injection of CTX; Groups C, D, and E were administered Dilong at doses of 100, 200, and 400 mg/kg respectively for 14 days after intraperitoneal injection of CTX. Results showed that after modeling, the movement speed of mice significantly decreased (P < 0.05), and the number of neurons in the hippocampus and cortex decreased. ⋯ Dilong significantly increased mitochondrial respiratory enzyme activity (P < 0.05), and the mitochondrial structure was restored to some extent. By significantly reducing NLRP3/TLR4/caspase1/pro caspase1/GSDMD (P < 0.05), it increased neuronal cell survival. This resulted in an increase in neuronal cell survival, thus exerting a protective effect on the brain.
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Estrogens and progesterone can have rapid effects on neuronal function and can modify the use of spatial navigation strategies dependent upon the prefrontal cortex, striatum, and hippocampus. Here, we assessed the effects of 17β-estradiol (E2), progesterone, and its metabolite allopregnanolone, on evoked excitatory postsynaptic potentials in the infralimbic region of the female rat prefrontal cortex. Field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of layer I were first characterized by recording responses at multiple depths between the cortical surface and the underlying white matter. ⋯ The effects of progesterone were not blocked by the nuclear progesterone receptor antagonist RU486 (1 µM). Both progesterone and allopregnanolone are known to activate membrane progesterone receptors, and we found that the membrane progesterone receptor agonist Org OD 02-0 facilitated EPSPs, and also occluded further increases induced by either progesterone or allopregnanolone. These results provide evidence that both progesterone and allopregnanolone facilitate synaptic responses in layer I of the infralimbic cortex by activating membrane progesterone receptors.