Pitx2 cholinergic interneurons are the source of C bouton synapses on brainstem motor neurons

IR and LZ were funded by the European Union, Seventh Framework Programme (FP7/2007–2013), by the European Union and Greek National Funds through the operational program “Education and Lifelong Learning” of the National Strategic Reference Framework, funding program: ARISTEIA II, and by Fondation Santé.Cholinergic neuromodulation has been described throughout the brain and has been implicated in various functions including attention, food intake and response to stress. Cholinergic modulation is also thought to be important for regulating motor systems, as revealed by studies of large cholinergic synapses on spinal motor neurons, called C boutons, which seem to control motor neuron excitability in a task-dependent manner. C boutons on spinal motor neurons stem from spinal interneurons that express the transcription factor Pitx2. C boutons have also been identified on the motor neurons of specific cranial nuclei. However, the source and roles of cranial C boutons are less clear. Previous studies suggest that they originate from Pitx2+ and Pitx2− neurons, in contrast to spinal cord C boutons that originate solely from Pitx2 neurons. Here, we address this controversy using mouse genetics, and demonstrate that brainstem C boutons are Pitx2+ derived. We also identify new Pitx2 populations and map the cholinergic Pitx2 neurons of the mouse brain. Taken together, our data present important new information about the anatomical organization of cholinergic systems which impact motor systems of the brainstem. These findings will enable further analyses of the specific roles of cholinergic modulation in motor control.Publisher PDFPeer reviewe

Gene Silencing in Chicken Brain Development

Despite the development of brain organoids and neural cultures derived from iPSCs (induced pluripotent stem cells), brain development can only be studied in an animal. The mouse is the most commonly used vertebrate model for the analysis of gene function because of the well-established genetic tools that are available for loss-of-function studies. However, studies of gene function during development can be problematic in mammals. Many genes are active during different stages of development. Absence of gene function during early development may cause aberrant neurogenesis or even embryonic lethality and thus prevent analysis of later stages of development. To avoid these problems, precise temporal control of gene silencing is required.In contrast to mammals, oviparous animals are accessible for experimental manipulations during embryonic development. The combination of accessibility and RNAi- or Crispr/Cas9-based gene silencing makes the chicken embryo a powerful model for developmental studies. Depending on the time window during which gene silencing is attempted, chicken embryos can be used in ovo or ex ovo in a domed dish for easier access during later stages of development. Both techniques allow for precise temporal control of gene silencing during embryonic development

Endoglycan plays a role in axon guidance by modulating cell adhesion

Axon navigation depends on the interactions between guidance molecules along the trajectory and specific receptors on the growth cone. However, our in vitro and in vivo studies on the role of Endoglycan demonstrate that in addition to specific guidance cue - receptor interactions, axon guidance depends on fine-tuning of cell-cell adhesion. Endoglycan, a sialomucin, plays a role in axon guidance in the central nervous system of chicken embryos, but it is neither an axon guidance cue nor a receptor. Rather, Endoglycan acts as a negative regulator of molecular interactions based on evidence from in vitro experiments demonstrating reduced adhesion of growth cones. In the absence of Endoglycan, commissural axons fail to properly navigate the midline of the spinal cord. Taken together, our in vivo and in vitro results support the hypothesis that Endoglycan acts as a negative regulator of cell-cell adhesion in commissural axon guidance

Speech deficits in multiple sclerosis: a narrative review of the existing literature

Abstract Multiple sclerosis (MS) is a chronic inflammatory and demyelinating autoimmune disease. MS patients deal with motor and sensory impairments, visual disabilities, cognitive disorders, and speech and language deficits. The study aimed to record, enhance, update, and delve into our present comprehension of speech deficits observed in patients with MS and the methodology (assessment tools) studies followed. The method used was a search of the literature through the databases for May 2015 until June 2022. The reviewed studies offer insight into speech impairments most exhibited by MS patients. Patients with MS face numerous communication changes concerning the phonation system (changes observed concerning speech rate, long pause duration) and lower volume. Moreover, the articulation system was affected by the lack of muscle synchronization and inaccurate pronunciations, mainly of vowels. Finally, there are changes regarding prosody (MS patients exhibited monotonous speech). Findings indicated that MS patients experience communication changes across various domains. Based on the reviewed studies, we concluded that the speech system of MS patients is impaired to some extent, and the patients face many changes that impact their conversational ability and the production of slower and inaccurate speech. These changes can affect MS patients’ quality of life

Development of a Multi-Enzymatic Approach for the Modification of Biopolymers with Ferulic Acid

A series of polymers, including chitosan (CS), carboxymethylcellulose (CMC) and a chitosan–gelatin (CS–GEL) hybrid polymer, were functionalized with ferulic acid (FA) derived from the enzymatic treatment of arabinoxylan through the synergistic action of two enzymes, namely, xylanase and feruloyl esterase. Subsequently, the ferulic acid served as the substrate for laccase from Agaricus bisporus (AbL) in order to enzymatically functionalize the above-mentioned polymers. The successful grafting of the oxidized ferulic acid products onto the different polymers was confirmed through ultraviolet–visible (UV–Vis) spectroscopy, attenuated total reflectance (ATR) spectroscopy, scanning electron microscopy (SEM) and nuclear magnetic resonance (NMR) spectroscopy. Additionally, an enhancement of the antioxidant properties of the functionalized polymers was observed according to the DDPH and ABTS protocols. Finally, the modified polymers exhibited strong antimicrobial activity against bacterial populations of Escherichia coli BL21DE3 strain, suggesting their potential application in pharmaceutical, cosmeceutical and food industries