Neuroscience
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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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Parkinson's disease (PD) is characterized by tremor, rigidity, and bradykinesia. PD is caused mainly by depletion of the nigrostriatal pathway. Conventional medications such as levodopa are highly effective in the early stage of PD; however, these medications fail to prevent the underlying neurodegeneration. ⋯ For example, although fetal ventral midbrain is efficacious in some patients, its ethical issues and the existence of graft-induced dyskinesias (GID) have prevented its use in large-scale clinical applications. ESCs have reliable isolation protocols and the potential to differentiate into dopaminergic progenitors. iPSCs and induced neural cells are suitable for autologous grafting. Here we review milestone improvements and emerging sources for cell-based PD therapy to serve as a framework for clinicians and a key reference to develop replacement therapy for other neurological disorders.
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Subcommissural organ (SCO)-spondin is a brain-specific glycoprotein produced during embryogenesis, that strongly contributes to neuronal development. The SCO becomes atrophic in adults, halting SCO-spondin production and its neuroprotective functions. Using rat and human neuronal cultures, we evaluated the neuroprotective effect of an innovative peptide derived from SCO-spondin against glutamate excitotoxicity. ⋯ The neuroprotective effect of NX210c was confirmed in human cortical neurons via the reduction of lactate dehydrogenase release and recovery of normal basal levels of apoptotic cells. Together, these results show that NX210 and NX210c protect against glutamate neurotoxicity through common and distinct mechanisms of action and that, most often, NX210c is more efficient than NX210. Proof of concept in central nervous system animal models are under investigation to evaluate the neuroprotective action of SCO-spondin-derived peptide.
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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.
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Dual orexinergic antagonists (DORAs) have been recently developed as a pharmacotherapy alternative to established hypnotics. Hypnotics are largely evaluated in preclinical rodent models in the dark/active period yet should be ideally evaluated in the light/inactive period, analogous to when sleep disruption occurs in humans. We describe here the hypnotic efficacy of DORA-22 in rodent models of sleep disturbance produced by cage changes in the light/inactive period. ⋯ EEG measures indicated that all DORA-22 doses largely promoted sleep in the first hour. The lowest dose (1 mg/kg) did not decrease sleep onset latency at the six-hour timepoint, suggesting no residual hypersomnolence. We described here DORA-22 hypnotic efficacy during the normal sleep period of nocturnal rats, and demonstrate that well-chosen (low) hypnotic doses of DORA-22 may be hypnotically effective yet have minimal lingering effects.