Neuroscience
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In amyotrophic lateral sclerosis (ALS), large motoneurons degenerate first, causing muscle weakness. Transgenic mouse models with a mutation in the gene encoding the enzyme superoxide dismutase 1 (SOD1) revealed that motoneurons innervating the fast-fatigable muscular fibres disconnect very early. The cause of this peripheric disconnection has not yet been established. ⋯ We conclude that dendritic overbranching and early hypoexcitability are common features of both low expressor SOD1 mutants (G85R and G93A-low). In the high-expressor SOD1G93A line, we found hyperexcitability in the sustained firing motoneurons at the same period, suggesting a delay in compensatory mechanisms. Overall, our results suggest that the hypoexcitability indicate an early dysfunction of the delayed-onset motoneurons and could account as early pathological signs of the disease.
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Cognitive dysfunction often accompanies diabetes. Both hypoglycemia and hyperglycemia cause cognitive dysfunctions. However, the underlying pathophysiology remains unclear. ⋯ Pathway enrichment analyses indicated that differentially expressed mRNAs associated-coding genes were associated with ferroptosis. Among ferroptosis signaling pathway genes, Slc40a1 gene (ferroportin) was downregulated. We show that ferroptosis is associated with diabetic cognitive dysfunction and Slc40a1 mediates ferroptosis in T1D.
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Alzheimer's disease (AD) is the most common neurodegenerative disease; thus, the search for a cure or causal therapy has become necessary. Despite intense research on this topic in recent decades, there is no curative therapy up today, and also no disease-modifying treatment has been approved. As promising approach passive immunization strategies have thereby come forth. ⋯ Further functional assays predict a protective effect of this antibody. Although, all four recombinant antibodies showed binding to amyloid-β, promising features were only detectable after conversion into a multimeric format. The multimeric scFv-Fc antibody exhibited thereby strong impact on amyloid-β clearance and inhibition of oligomerization.
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The left posterior inferior frontal gyrus in the prefrontal cortex is a key region for phonological aspects of language processing. A previous study has shown that alpha-tACS over the prefrontal cortex applied before task processing facilitated phonological decision-making and increased task-related theta power. However, it is unclear how alpha-tACS affects phonological processing when applied directly during the task. ⋯ As an unexpected finding, 16.18 Hz significantly impaired task accuracy relative to sham stimulation, without affecting response speed. There was no significant difference in phonological task performance between 10 Hz and 16.18 Hz tACS or between 10 Hz and sham stimulation. Our results support the functional relevance of the left prefrontal cortex for phonological decisions and suggest that online beta-tACS may modulate language comprehension.
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Inflammasomes are key components of the innate immune system and activation of these multiprotein platforms is a crucial event in the etiopathology of amyotrophic lateral sclerosis (ALS). Inflammasomes consist of a pattern recognition receptor (PRR), the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and caspase 1. Exogenous or endogenous "danger signals" can trigger inflammasome assembly and promote maturation and release of pro-inflammatory cytokines, including interleukin 1β. ⋯ Staining of AIM2 was detected in all types of glia, whereas glial type-specific labelling was observed for NLRP1 and NLRC4. Our findings revealed pathology-related and cell type-specific differences in the expression of subsets of PRRs. Besides NLRP3, NLRC4 appears to be linked more closely to ALS pathogenesis.