Neuronal Origin Research Articles

M/EEG source localization for both subcortical and cortical sources using a convolutional neural network with a realistic head conductivity model

While electroencephalography (EEG) and magnetoencephalography (MEG) are well-established noninvasive methods in neuroscience and clinical medicine, they suffer from low spatial resolution. Electrophysiological source imaging (ESI) addresses this by noninvasively exploring the neuronal origins of M/EEG signals. Although subcortical structures are crucial to many brain functions and neuronal diseases, accurately localizing subcortical sources of M/EEG remains particularly challenging, and the feasibility is still a subject of debate. Traditional ESIs, which depend on explicitly defined regularization priors, have struggled to set optimal priors and accurately localize brain sources. To overcome this, we introduced a data-driven, deep learning-based ESI approach without the need for these priors. We proposed a four-layered convolutional neural network (4LCNN) designed to locate both subcortical and cortical sources underlying M/EEG signals. We also employed a sophisticated realistic head conductivity model using the state-of-the-art segmentation method of ten different head tissues from individual MRI data to generate realistic training data. This is the first attempt at deep learning-based ESI targeting subcortical regions. Our method showed excellent accuracy in source localization, particularly in subcortical areas compared to other methods. This was validated through M/EEG simulations, evoked responses, and invasive recordings. The potential for accurate source localization of the 4LCNNs demonstrated in this study suggests future contributions to various research endeavors such as the clinical diagnosis, understanding of the pathophysiology of various neuronal diseases, and basic brain functions.

The genetics of spatiotemporal variation in cortical thickness in youth

Prior studies have shown strong genetic effects on cortical thickness (CT), structural covariance, and neurodevelopmental trajectories in childhood and adolescence. However, the importance of genetic factors on the induction of spatiotemporal variation during neurodevelopment remains poorly understood. Here, we explore the genetics of maturational coupling by examining 308 MRI-derived regional CT measures in a longitudinal sample of 677 twins and family members. We find dynamic inter-regional genetic covariation in youth, with the emergence of regional subnetworks in late childhood and early adolescence. Three critical neurodevelopmental epochs in genetically-mediated maturational coupling were identified, with dramatic network strengthening near eleven years of age. These changes are associated with statistically-significant (empirical p-value <0.0001) increases in network strength as measured by average clustering coefficient and assortativity. We then identify genes from the Allen Human Brain Atlas with similar co-expression patterns to genetically-mediated structural covariation in children. This set was enriched for genes involved in potassium transport and dendrite formation. Genetically-mediated CT-CT covariance was also strongly correlated with expression patterns for genes located in cells of neuronal origin.

Comparing alpha-synuclein-interactomes between multiple systems atrophy and Parkinson's disease reveals unique and shared pathological features.

Primary synucleinopathies, such as Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are neurodegenerative disorders with some shared clinical and pathological features. Aggregates of alpha-synuclein (αsyn) phosphorylated at serine 129 (PSER129) are the hallmark of synucleinopathies, which for PD/DLB are found predominantly in neurons (Neuronal cytoplasmic inclusions "NCIs"), but for MSA, aggregates are primarily found in oligodendroglia (Glial cytoplasmic inclusions "GCIs"). It remains unclear if the distinct pathological presentation of PD/DLB and MSA are manifestations of distinct or shared pathological processes. We hypothesize that the distinct synucleinopathies MSA and PD/DLB share common molecular features. Using the in-situ proximity labeling technique biotinylation by antibody recognition (BAR), we compare aggregated αsyn-interactomes (BAR-PSER129) and total αsyn-interactomes (BAR-MJFR1) between MSA (n=5) and PD/DLB (n=10) in forebrain and midbrain structures. For BAR-PSER129 and BAR-MJFR1 captures, αsyn was the most significantly enriched protein in PD/DLB and MSA. In PD/DLB, BAR-PSER129 identified 194 αsyn-aggregate-interacting proteins, while BAR-MJFR1 identified 245 αsyn interacting proteins. In contrast, in the MSA brain, only 38 and 175 proteins were identified for each capture, respectively. When comparing MSA and PD/DLB, a high overlap (59.5%) was observed between BAR-MJFR1 captured proteins, whereas less overlap (14.4%) was observed for BAR-PSER129. Direct comparison between MSA and PD/DLB revealed 79 PD/DLB-associated proteins and only three MSA-associated proteins (CBR1, CRYAB, and GFAP). Pathway enrichment analysis revealed PD/DLB interactions were dominated by vesicle/SNARE-associated pathways, in contrast to MSA, which strongly enriched for metabolic/catabolic, iron, and cellular oxidant detoxification pathways. A subnetwork of cytosolic antioxidant enzymes called peroxiredoxins drove cellular detoxification pathways in MSA. A common network of 26 proteins, including neuronal-specific proteins (e.g., SNYGR3) with HSPA8 at the core, was shared between MSA and DLB/PD. Extracellular exosome pathways were universally enriched regardless of disease or BAR target protein. Synucleinopathies have divergent and convergent αsyn-aggregate interactions, indicating unique and shared pathogenic mechanisms. MSA uniquely involves oxidant detoxification processes in glial cells, while vesicular processes in neurons dominate PD/DLB. Shared interactions, specifically SNYGR3 (i.e., a neuronal protein), between MSA and PD/DLB suggest neuronal axons origin for both diseases. In conclusion, we provide αsyn aggregates protein interaction maps for two distinct synucleinopathies.

Development and characterization of primary cell culture from the spinal cord of Asian seabass, Lates calcarifer.

Asian seabass, Lates calcarifer, is one of the most important fish species in aquaculture. An attempt was made to develop a primary cell culture from the spinal cord of Lates calcarifer by the enzymatic and mechanical dissociation method. The primary cell culture was sub-cultured for 20 times in Leibovitz's L-15 medium with 20% fetal bovine serum (FBS) and 0.5nM of human neurotrophin-3 at 28°C. The primary cell culture was cryopreserved at different passage levels and recovery of cells after long-term storage was estimated about 75-85%. The authenticity of origin of primary cell culture from L. calcarifer was confirmed by polymerase chain reaction assay using species-specific mitochondrial 12S rRNA primer. The primary cell culture was designated as seabass spinal cord cells (SBSC). The cells morphologically resembled the neurons due to their neural-like prolongations and star-like structure. Immunophenotypic analysis of the SBSC revealed that they are of neuronal origin. The SBSC were found to be highly susceptible to striped jack nervous necrosis virus (SJNNV) and infection in the cells was confirmed by RT-PCR. In conclusion, this is the first innovative euryhaline fish neuronal primary cell culture of L. calcarifer now available for neurophysiological and neurotoxicological studies.

Blood-based protein biomarkers during the acute ischemic stroke treatment window: a systematic review.

Rapid and accurate acute ischemic stroke (AIS) diagnosis is needed to expedite emergent thrombolytic and mechanical thrombectomy treatment. Changes in blood-based protein biomarkers during the first 24 h of AIS, the time window for treatment, could complement imaging techniques and facilitate rapid diagnosis and treatment. We performed a systematic review according to PRISMA guidelines. MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched for eligible studies comparing levels of blood-based protein biomarkers in AIS patients with levels in healthy controls and stroke mimics. Protein biomarkers from the following pathophysiological categories were included: neurovascular inflammation (MMP-9, TNF-alpha), endothelial integrity (VCAM-1, ICAM-1), cell migration (E-Selectin, P-Selectin, L-Selectin), markers of glial and neuronal origin (GFAP, S100, S100B, NSE), and cardiac dysfunction (BNP, NT-proBNP). The literature search was limited to English-language publications before November 7th, 2023. A total of 61 studies from 20 different countries were identified, which included in total, 4,644 AIS patients, 2,242 stroke mimics, and 2,777 controls. Studies investigating TNF-alpha, MMP-9, VCAM-1, ICAM-1, E-Selectin, L-Selectin, GFAP, NSE, and S100B showed pronounced methodological heterogeneity, making between-study comparisons difficult. However, in 80% of NT-proBNP and BNP studies, and all P-selectin studies, higher biomarker levels were observed in AIS patients compared to healthy controls and/or patients with stroke mimics. None of the biomarkers included showed sufficient evidence for additional diagnostic benefit for AIS. Comprehensive standardized global multicenter studies are needed to (1) permit comparability, (2) enable valid statements about protein-based biomarkers, and (3) reflect real-world scenarios.

Neuronal Distribution in Colorectal Cancer: Associations With Clinicopathological Parameters and Survival

Over the past years, insights in the cancer neuroscience field increased rapidly, and a potential role for neurons in colorectal carcinogenesis has been recognized. However, knowledge on the neuronal distribution, subtypes, origin, and associations with clinicopathological characteristics in human studies is sparse. In this study, colorectal tumor tissues from the Netherlands Cohort Study on diet and cancer (n = 490) and an in-cohort validation population (n = 529) were immunohistochemically stained for the pan-neuronal markers neurofilament (NF) and protein gene product 9.5 (PGP9.5) to study the association between neuronal marker expression and clinicopathological characteristics. In addition, tumor and healthy colon tissues were stained for neuronal subtype markers, and their immunoreactivity in colorectal cancer (CRC) stroma was analyzed. NF-positive and PGP9.5-positive nerve fibers were found within the tumor stroma and mostly characterized by the neuronal subtype markers vasoactive intestinal peptide and neuronal nitric oxide synthase, suggesting that inhibitory neurons are the most prominent neuronal subtype in CRC. NF and PGP9.5 protein expression were not consistently associated with tumor stage, sublocation, differentiation grade, and median survival. NF immunoreactivity was associated with a worse CRC-specific survival in the study cohort (P = .025) independent of other prognostic factors (hazard ratio, 2.31; 95% CI, 1.33-4.03; P = .003), but these results were not observed in the in-cohort validation group. PGP9.5, in contrast, was associated with a worse CRC-specific survival in the in-cohort validation (P = .046) but not in the study population. This effect disappeared in multivariate analyses (hazard ratio, 0.81; 95% CI, 0.50-1.32; P = .393), indicating that this effect was dependent on other prognostic factors. This study demonstrates that the tumor stroma of CRC patients mainly harbors inhibitory neurons and that NF as a single marker is significantly associated with a poorer CRC-specific survival in the study cohort but necessitates future validation.

Prospects and challenges in using neuronal extracellular vesicles in biomarker research.

Extracellular vesicles (EVs) hold promise as a source of disease biomarkers. The diverse molecular cargo of EVs can potentially indicate the status of their tissue of origin, even against the complex background of whole plasma. The main tools currently available for assessing biomarkers of brain health include brain imaging and analysis of the cerebrospinal fluid of patients. Given the costs and difficulties associated with these methods, isolation of EVs of neuronal origin (NEVs) from the blood is an attractive approach to identify brain-specific biomarkers. This perspective describes current key challenges in EV- and NEV-based biomarker research. These include the relative low abundance of EVs, the lack of validated isolation methods, and the difficult search for an adequate target for immunocapturing NEVs. We discuss that these challenges must be addressed before NEVs can fulfill their potential for biomarker research. HIGHLIGHTS: NEVs are promising sources of biomarkers for brain disorders. Immunocapturing NEVs from complex biofluids presents several challenges. The choice of surface target for capture will determine NEV yield. Contamination by non-EV sources is relevant for biomarkers at low concentrations.

Comparative study of HIV-1 inhibition efficiency by carrageenans from red seaweeds family gigartinaceae, Tichocarpaceae and Phyllophoraceae

The efficiency of human immunodeficiency virus-1 (HIV-1) inhibition by sulfated polysaccharides isolated from the various families of red algae of the Far East Pacific coast were studied. The anti-HIV-1 activity of kappa and lambda-carrageenans from Chondrus armatus, original highly sulfated X-carrageenan with low content of 3,6-anhydrogalactose from Tichocarpus crinitus and i/κ–carrageenan with hybrid structure isolated from Ahnfeltiopsis flabelliformis was found. The antiviral action of these polysaccharides and its low-weight oligosaccharide was compared with commercial κ-carrageenan. Here we used the HIV-1-based lentiviral particles and evaluated that these carrageenans in non-toxic concentrations significantly suppress the transduction potential of lentiviral particles pseudotyped with different envelope proteins, targeting cells of neuronal or T-cell origin. The antiviral action of these carrageenans was confirmed using the chimeric replication competent Mo-MuLV (Moloney murine leukemia retrovirus) encoding marker eGFP protein. We found that X-carrageenans from T. crinitus and its low weight derivative and λ-carrageenan from C. armatus effectively suppress the infection caused by retrovirus. The obtained data suggest that the differences in the suppressive effect of carrageenans on the transduction efficiency of HIV-1 based lentiviral particles may be related to the structural features of the studied polysaccharides.

Solitary intraosseous neurofibroma of the oral cavity: rare localization in the maxilla

BackgroundNeurofibroma is a common benign tumor of neuronal origin that can occur as a solitary tumor or as a component of the generalized syndrome of neurofibromatosis. Neurofibromas are primarily located in the subcutaneous soft tissues and commonly involve extra-oral sites. Solitary intraosseous neurofibromas of the oral cavity are infrequent, with occurrences in the maxilla being exceedingly rare.Case presentationA 22-year-old male patient presented with an asymptomatic mass in the maxilla. Cone-beam computed tomography revealed a round, well-outlined, radiolucent lesion with expansive growth. The neoplasm with the complete capsule was completely removed and confirmed as a neurofibroma based on histopathological and immunohistochemical findings. The reported cases of solitary intraosseous neurofibromas located in the maxilla published in the English literature were compiled to assist in the diagnosis of solitary intraosseous neurofibromas of the maxilla. Nine months after the surgery, there were no signs of tumor recurrence or malignant transformation.ConclusionsThis report emphasizes that rare locations of neurofibromas, such as solitary intraosseous neurofibromas in the maxilla, typically demonstrate nonspecific clinical and radiological features. Clinicians should consider solitary intraosseous neurofibromas as possible differential diagnoses and recognize the histopathological and immunohistochemical features to confirm the correct diagnosis. A longer follow-up period is required because of the potential for local recurrence and malignant transformation of these tumors.

Single-extracellular vesicle (EV) analyses validate the use of L1 Cell Adhesion Molecule (L1CAM) as a reliable biomarker of neuron-derived EVs.

Isolation of neuron-derived extracellular vesicles (NDEVs) with L1 Cell Adhesion Molecule (L1CAM)-specific antibodies has been widely used to identify blood biomarkers of CNS disorders. However, full methodological validation requires demonstration of L1CAM in individual NDEVs and lower levels or absence of L1CAM in individual EVs from other cells. Here, we used multiple single-EV techniques to establish the neuronal origin and determine the abundance of L1CAM-positive EVs in human blood. L1CAM epitopes of the ectodomain are shown to be co-expressed on single-EVs with the neuronal proteins β-III-tubulin, GAP43, and VAMP2, the levels of which increase in parallel with the enrichment of L1CAM-positive EVs. Levels of L1CAM-positive EVs carrying the neuronal proteins VAMP2 and β-III-tubulin range from 30% to 63%, in contrast to 0.8%-3.9% of L1CAM-negative EVs. Plasma fluid-phase L1CAM does not bind to single-EVs. Our findings support the use of L1CAM as a target for isolating plasma NDEVs and leveraging their cargo to identify biomarkers reflecting neuronal function.

Lipidomic Analysis of Plasma Extracellular Vesicles Derived from Alzheimer's Disease Patients.

Analysis of blood-based indicators of brain health could provide an understanding of early disease mechanisms and pinpoint possible intervention strategies. By examining lipid profiles in extracellular vesicles (EVs), secreted particles from all cells, including astrocytes and neurons, and circulating in clinical samples, important insights regarding the brain's composition can be gained. Herein, a targeted lipidomic analysis was carried out in EVs derived from plasma samples after removal of lipoproteins from individuals with Alzheimer's disease (AD) and healthy controls. Differences were observed for selected lipid species of glycerolipids (GLs), glycerophospholipids (GPLs), lysophospholipids (LPLs) and sphingolipids (SLs) across three distinct EV subpopulations (all-cell origin, derived by immunocapture of CD9, CD81 and CD63; neuronal origin, derived by immunocapture of L1CAM; and astrocytic origin, derived by immunocapture of GLAST). The findings provide new insights into the lipid composition of EVs isolated from plasma samples regarding specific lipid families (MG, DG, Cer, PA, PC, PE, PI, LPI, LPE, LPC), as well as differences between AD and control individuals. This study emphasizes the crucial role of plasma EV lipidomics analysis as a comprehensive approach for identifying biomarkers and biological targets in AD and related disorders, facilitating early diagnosis and potentially informing novel interventions.

Neural crest origin of sympathetic neurons at the dawn of vertebrates.

The neural crest is an embryonic stem cell population unique to vertebrates1 whose expansion and diversification are thought to have promoted vertebrate evolution by enabling emergence of new cell types and structures such as jaws and peripheral ganglia2. Although jawless vertebrates have sensory ganglia, convention has it that trunk sympathetic chain ganglia arose only in jawed vertebrates3-8. Here, by contrast, we report the presence of trunk sympathetic neurons in the sea lamprey, Petromyzon marinus, an extant jawless vertebrate. These neurons arise from sympathoblasts near the dorsal aorta that undergo noradrenergic specification through a transcriptional program homologous to that described in gnathostomes. Lamprey sympathoblasts populate the extracardiac space and extend along the length of the trunk in bilateral streams, expressing the catecholamine biosynthetic pathway enzymes tyrosine hydroxylase and dopamine β-hydroxylase. CM-DiI lineage tracing analysis further confirmed that these cells derive from the trunk neural crest. RNA sequencing of isolated ammocoete trunk sympathoblasts revealed gene profiles characteristic of sympathetic neuron function. Our findings challenge the prevailing dogma that posits that sympathetic ganglia are a gnathostome innovation, instead suggesting that a late-developing rudimentary sympathetic nervous system may have been characteristic of the earliest vertebrates.

Lineage Analysis and Birthdating of Drosophila Central Complex Lineages.

From insects to humans, the nervous system generates complex behaviors mediated by distinct neural circuits that are composed of diverse cell types. During development, the spatiotemporal gene expression of the neural progenitors expands the diversity of neuronal and glial subtypes. Various neural stem cell-intrinsic and -extrinsic gene programs have been identified that are thought to play a major role in generating diverse neuronal and glial cell types. Drosophila has served as an excellent model system for discovering the fundamental principles of nervous system development and function. The sophisticated genetic tools allow us to link the origin and birth timing (the time when a particular neuron is born during development) of neuron types to unique neural stem cells (NSCs) and to a developmental time. In Drosophila, a special class of NSCs called Type II NSCs has adopted a more advanced division mode to generate lineages for the higher-order brain center, the central complex, which is an evolutionarily conserved brain region found in all insects. Type II NSCs, similar to the human outer radial glia, generate intermediate neural progenitors (INPs), which divide many times to produce about eight to 10 progeny. Both Type II NSCs and INPs express distinct transcription factors and RNA-binding proteins that have been proposed to regulate the specification of cell types populating the adult central complex. Here, we describe the recently invented lineage filtering system, called cell class-lineage intersection (CLIn), which enables the tracking and birthdating of the Type II NSC lineages. Using CLIn, one can easily generate clones of different Type II NSCs and identify not only the origins of neurons of interest but also their birth time.

Large-scale coupling of prefrontal activity patterns as a mechanism for cognitive control in health and disease: evidence from rodent models.

Cognitive control of behavior is crucial for well-being, as allows subject to adapt to changing environments in a goal-directed way. Changes in cognitive control of behavior is observed during cognitive decline in elderly and in pathological mental conditions. Therefore, the recovery of cognitive control may provide a reliable preventive and therapeutic strategy. However, its neural basis is not completely understood. Cognitive control is supported by the prefrontal cortex, structure that integrates relevant information for the appropriate organization of behavior. At neurophysiological level, it is suggested that cognitive control is supported by local and large-scale synchronization of oscillatory activity patterns and neural spiking activity between the prefrontal cortex and distributed neural networks. In this review, we focus mainly on rodent models approaching the neuronal origin of these prefrontal patterns, and the cognitive and behavioral relevance of its coordination with distributed brain systems. We also examine the relationship between cognitive control and neural activity patterns in the prefrontal cortex, and its role in normal cognitive decline and pathological mental conditions. Finally, based on these body of evidence, we propose a common mechanism that may underlie the impaired cognitive control of behavior.

Developmental neuroscience: Building sex-specific adult circuitry from common larval origins

The development of sex-specific neural circuitry is critical for reproductive behaviors. A new study traces the developmental origin of female-specific neurons that underlie an adult mating behavior to larval neurons common to both sexes in Drosophila.

The SLC6A1 Mutation Schizophrenia case — A Comprehensive Case Study With iPSC Generation

IntroductionThe main finding of a large-scale collaborative study (Rees et al. Nat Neurosci 2020;23(2) 179-184), which focused on de novo mutations in schizophrenia, was the discovery of an enrichment of these mutations in the SLC6A1 gene. This gene encodes the gamma-aminobutyric acid (GABA) transporter GAT1, thereby encouraging further research into novel schizophrenia targets within the GABA pathway. However, the gene was not highlighted in recent schizophrenia genetic studies, while typically pathogenic SLC6A1 mutations result in epilepsy, motor dysfunction, autistic spectrum disorder (ASD) and developmental delay. The absence of genetic replication for SLC6A1’s involvement in schizophrenia and the differing clinical spectrum for SLC6A1 mutations led us to study in depth one of the only three original probands from the Rees et al. 2020 study.ObjectivesIn our comprehensive case study, we delved deep into the relationship between the SLC6A1 mutation and schizophrenia.MethodsOur subject, a patient who first presented with acute mania symptoms at age 15 and was later diagnosed with schizophrenia, carried the SLC6A1 Arg211Cys mutation. Over a detailed 25-year follow-up, we conducted an array of assessments and tests, including cognitive testing, personality assessments, EEG, and 1H-MRS.ResultsNotably, we discovered abnormal GABA levels, potentially indicating a dysfunction in GABA reuptake, adding a new layer of complexity to our understanding. Further analysis revealed a significant correlation between the patient’s clinical picture and a polygenic background, rather than the SLC6A1 mutation. Despite having a high polygenic risk score for bipolar disorder, the dominant features of his condition were more representative of schizophrenia. Interestingly, neither the patient nor his father, who also showed a higher BP PRS, had a diagnosis of bipolar disorder. The pathogenic significance of the mutation warrants investigation in cells of neuronal origin. We generated induced pluripotent stem cells (iPSC) from the patient and his parents. This approach provides us with a platform for future investigations into the pathogenic significance of the mutation in neuronal cells. The Human Pluripotent Stem Cell Registry accession numbers of those cells are MHRCCGi001-A (patient), MHRCCGi005-A (mother) and MHRCCGi004-A (father).ConclusionsIn the presented case the clinical picture is rather explained by the polygenic background than by the SLC6A1 Arg211Cys mutation. The study is supported by Russian Science Foundation, grant 21-15-00124 (https://rscf.ru/project/21-15-00124)Disclosure of InterestNone Declared

The anatomy, neurophysiology, and cellular mechanisms of intradental sensation.

Somatosensory innervation of the oral cavity enables the detection of a range of environmental stimuli including minute and noxious mechanical forces. The trigeminal sensory neurons underlie sensation originating from the tooth. Prior work has provided important physiological and molecular characterization of dental pulp sensory innervation. Clinical dental experiences have informed our conception of the consequence of activating these neurons. However, the biological role of sensory innervation within the tooth is yet to be defined. Recent transcriptomic data, combined with mouse genetic tools, have the capacity to provide important cell-type resolution for the physiological and behavioral function of pulp-innervating sensory neurons. Importantly, these tools can be applied to determine the neuronal origin of acute dental pain that coincides with tooth damage as well as pain stemming from tissue inflammation (i.e., pulpitis) toward developing treatment strategies aimed at relieving these distinct forms of pain.

Structure of Soft Tissues in Congenital Unilateral Cleft Lip, Light and Electron Microscopic Observations

Abstract Cleft lip (CL), palate (CP), or both (CLP) are one of the most common congenital abnormalities in humans, causing a heavy burden to the affected and their next of kin. We examined biopsy material from CL of seven children: Six 2 to 6 month-old babies and one 4-year-old boy. The samples were taken at the first surgical cleft lip repair. Light microscopy (LM) haematoxylin and eosin stained paraffin sections and toluidine blue stained 0.5–1 μm Durcupan sections from material processed for transmission electron microscopy (TEM), revealed abnormal “ragged” wavy muscle fibres in all seven children. The routine TEM confirmed our results LM; we found no other changes in the soft tissues in TEM; blood vessels of loose connective tissue and nerve fibres were normal. Therefore, we believe that myopathic changes in the cleft lip muscle fibres cannot be of neuronal origin.

Enhanced neuronal differentiation using plasma synthesized amino polymers

Different pyrrole and allylamine polymeric materials, were synthesized by plasma polymerization with different powers and doped with iodine. The polymers were characterized physicochemically. A cell line of neuronal origin (N1E-115) was cultured on them to evaluate the effects of the materials on neuronal differentiation. Following a differentiation stimulus, immunofluorescence was performed, and the lengths of neurites, as well as the complexity of the network formed and the number of nuclei, were measured and analyzed to provide a differentiation index. The results showed that the polymeric materials exhibited different physicochemical characteristics depending on the synthesis conditions and enhanced neuronal differentiation.

Evolution and development of extraocular motor neurons, nerves and muscles in vertebrates

The purpose of this review is to analyze the origin of ocular motor neurons, define the pattern of innervation of nerve fibers that project to the extraocular eye muscles (EOMs), describe congenital disorders that alter the development of ocular motor neurons, and provide an overview of vestibular pathway inputs to ocular motor nuclei. Six eye muscles are innervated by axons of three ocular motor neurons, the oculomotor (CNIII), trochlear (CNIV), and abducens (CNVI) neurons. Ocular motor neurons (CNIII) originate in the midbrain and innervate the ipsilateral orbit, except for the superior rectus and the levator palpebrae, which are contralaterally innervated. Trochlear motor neurons (CNIV) originate at the midbrain-hindbrain junction and innervate the contralateral superior oblique muscle. Abducens motor neurons (CNVI) originate variously in the hindbrain of rhombomeres r4–6 that innervate the posterior (or lateral) rectus muscle and innervate the retractor bulbi. Genes allow a distinction between special somatic (CNIII, IV) and somatic (CNVI) ocular motor neurons. Development of ocular motor neurons and their axonal projections to the EOMs may be derailed by various genetic causes, resulting in the congenital cranial dysinnervation disorders. The ocular motor neurons innervate EOMs while the vestibular nuclei connect with the midbrain-brainstem motor neurons.