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American Journal of Human Biology : the... 2011Von Economo neurons (VENs) are defined by their thin, elongated cell body and long dendrites projecting from apical and basal ends. These distinctive neurons are mostly... (Review)
Review
OBJECTIVES
Von Economo neurons (VENs) are defined by their thin, elongated cell body and long dendrites projecting from apical and basal ends. These distinctive neurons are mostly present in anterior cingulate (ACC) and fronto-insular (FI) cortex, with particularly high densities in cetaceans, elephants, and hominoid primates (i.e., humans and apes). This distribution suggests that VENs contribute to specializations of neural circuits in species that share both large brain size and complex social cognition, possibly representing an adaptation to rapidly relay socially-relevant information over long distances across the brain. Recent evidence indicates that unique patterns of protein expression may also characterize VENs, particularly involving molecules that are known to regulate gut and immune function.
METHODS
In this study, we used quantitative stereologic methods to examine the expression of three such proteins that are localized in VENs-activating-transcription factor 3 (ATF3), interleukin 4 receptor (IL4Rα), and neuromedin B (NMB). We quantified immunoreactivity against these proteins in different morphological classes of ACC layer V neurons of hominoids.
RESULTS
Among the different neuron types analyzed (pyramidal, VEN, fork, enveloping, and other multipolar), VENs showed the greatest percentage that displayed immunostaining. Additionally, a higher proportion of VENs in humans were immunoreactive to ATF3, IL4Rα, and NMB than in other apes. No other ACC layer V neuron type displayed a significant species difference in the percentage of immunoreactive neurons.
CONCLUSIONS
These findings demonstrate that phylogenetic variation exists in the protein expression profile of VENs, suggesting that humans might have evolved biochemical specializations for enhanced interoceptive sensitivity.
Topics: Activating Transcription Factor 3; Adult; Animals; Cell Count; Cerebral Cortex; Female; Hominidae; Humans; Hylobatidae; Imaging, Three-Dimensional; Immunohistochemistry; Male; Middle Aged; Neurokinin B; Neurons; Receptors, Interleukin-4; Social Behavior; Young Adult
PubMed: 21140465
DOI: 10.1002/ajhb.21135 -
BMC Neuroscience May 2023Histone deacetylase (HDAC) inhibitors affect cell homeostasis, gene expression, and cell cycle progression and promote cell terminal differentiation or apoptosis....
Histone deacetylase (HDAC) inhibitors affect cell homeostasis, gene expression, and cell cycle progression and promote cell terminal differentiation or apoptosis. However, the effect of HDAC inhibition on SH-SY5Y cells, which are neuroblastoma cells capable of differentiating into neurons under specific conditions, such as in the presence of retinoic acid (RA), is unknown. In this study, we hypothesized that HDAC inhibitors induced the neuronal differentiation of SH-SY5Y cells. To test this hypothesis, we used phase contrast microscopy, immunocytochemistry (ICC), qPCR, and western blotting analysis. MS-275 and valproic acid (VPA), two HDAC inhibitors, were selected to evaluate neuronal differentiation. It was confirmed that cells treated with MS-275 or VPA differentiated into mature neurons, which were distinguished by bipolar or multipolar morphologies with elongated branches. In addition, the mRNA expression of neuronal markers (Tuj1 and NEFH) and the oligodendrocyte marker (CNP) was significantly increased with MS-275 or VPA treatment compared to that with RA treatment. In addition, the protein expression of the other neuronal markers, Tuj1 and NeuN, was highly increased with HDAC inhibitor treatments compared to that with RA treatment. Furthermore, we confirmed that noncanonical Wnt signaling was upregulated by HDAC inhibitors via MAPK signaling and the Wnt/JNK pathway. Therefore, both MS-275 and VPA promoted the differentiation of SH-SY5Y cells into mature neurons via the Wnt signaling pathway.
Topics: Humans; Histone Deacetylase Inhibitors; Wnt Signaling Pathway; Neuroblastoma; Neurons; Valproic Acid; Cell Differentiation; Tretinoin; Cell Line, Tumor
PubMed: 37127577
DOI: 10.1186/s12868-023-00798-0 -
The Journal of Neuroscience : the... Oct 2022The axon initial segment (AIS) generates action potentials and maintains neuronal polarity by regulating the differential trafficking and distribution of proteins,...
The axon initial segment (AIS) generates action potentials and maintains neuronal polarity by regulating the differential trafficking and distribution of proteins, transport vesicles, and organelles. Injury and disease can disrupt the AIS, and the subsequent loss of clustered ion channels and polarity mechanisms may alter neuronal excitability and function. However, the impact of AIS disruption on axon regeneration after injury is unknown. We generated male and female mice with AIS-deficient multipolar motor neurons by deleting AnkyrinG, the master scaffolding protein required for AIS assembly and maintenance. We found that after nerve crush, neuromuscular junction reinnervation was significantly delayed in AIS-deficient motor neurons compared with control mice. In contrast, loss of AnkyrinG from pseudo-unipolar sensory neurons did not impair axon regeneration into the intraepidermal nerve fiber layer. Even after AIS-deficient motor neurons reinnervated the neuromuscular junction, they failed to functionally recover because of reduced synaptic vesicle protein 2 at presynaptic terminals. In addition, mRNA trafficking was disrupted in AIS-deficient axons. Our results show that, after nerve injury, an intact AIS is essential for efficient regeneration and functional recovery of axons in multipolar motor neurons. Our results also suggest that loss of polarity in AIS-deficient motor neurons impairs the delivery of axonal proteins, mRNAs, and other cargoes necessary for regeneration. Thus, therapeutic strategies for axon regeneration must consider preservation or reassembly of the AIS. Disruption of the axon initial segment is a common event after nervous system injury. For multipolar motor neurons, we show that axon initial segments are essential for axon regeneration and functional recovery after injury. Our results may help explain injuries where axon regeneration fails, and suggest strategies to promote more efficient axon regeneration.
Topics: Male; Female; Mice; Animals; Axons; Axon Initial Segment; Ankyrins; Nerve Regeneration; Synapses; Ion Channels; Motor Neurons; RNA, Messenger
PubMed: 36096668
DOI: 10.1523/JNEUROSCI.1261-22.2022 -
Proceedings of the National Academy of... Mar 2023During mitosis, cells round up and utilize the interphase adhesion sites within the fibrous extracellular matrix (ECM) as guidance cues to orient the mitotic spindles....
During mitosis, cells round up and utilize the interphase adhesion sites within the fibrous extracellular matrix (ECM) as guidance cues to orient the mitotic spindles. Here, using suspended ECM-mimicking nanofiber networks, we explore mitotic outcomes and error distribution for various interphase cell shapes. Elongated cells attached to single fibers through two focal adhesion clusters (FACs) at their extremities result in perfect spherical mitotic cell bodies that undergo significant 3-dimensional (3D) displacement while being held by retraction fibers (RFs). Increasing the number of parallel fibers increases FACs and retraction fiber-driven stability, leading to reduced 3D cell body movement, metaphase plate rotations, increased interkinetochore distances, and significantly faster division times. Interestingly, interphase kite shapes on a crosshatch pattern of four fibers undergo mitosis resembling single-fiber outcomes due to rounded bodies being primarily held in position by RFs from two perpendicular suspended fibers. We develop a cortex-astral microtubule analytical model to capture the retraction fiber dependence of the metaphase plate rotations. We observe that reduced orientational stability, on single fibers, results in increased monopolar mitotic defects, while multipolar defects become dominant as the number of adhered fibers increases. We use a stochastic Monte Carlo simulation of centrosome, chromosome, and membrane interactions to explain the relationship between the observed propensity of monopolar and multipolar defects and the geometry of RFs. Overall, we establish that while bipolar mitosis is robust in fibrous environments, the nature of division errors in fibrous microenvironments is governed by interphase cell shapes and adhesion geometries.
Topics: Cell Nucleus Division; Mitosis; Centrosome; Aircraft; Axons
PubMed: 36848565
DOI: 10.1073/pnas.2120536120 -
Science (New York, N.Y.) Apr 2022Terreros-Roncal . investigated the impacts of human neurodegeneration on immunostainings assumed to be associated with neurogenesis. However, the study provides no...
Terreros-Roncal . investigated the impacts of human neurodegeneration on immunostainings assumed to be associated with neurogenesis. However, the study provides no evidence that putative proliferating cells are linked to neurogenesis, that multipolar nestin astrocytes are progenitors, or that mature-looking doublecortin neurons are adult-born. Their histology-marker expression differs from what is observed in species where adult hippocampal neurogenesis is well documented.
Topics: Adult; Astrocytes; Hippocampus; Humans; Neurodegenerative Diseases; Neurogenesis; Neurons
PubMed: 35420933
DOI: 10.1126/science.abn8861 -
Control of Neuronal Migration and Aggregation by Reelin Signaling in the Developing Cerebral Cortex.Frontiers in Cell and Developmental... 2017The mammalian cerebral neocortex has a well-organized laminar structure, achieved by the highly coordinated control of neuronal migration. During cortical development,... (Review)
Review
The mammalian cerebral neocortex has a well-organized laminar structure, achieved by the highly coordinated control of neuronal migration. During cortical development, excitatory neurons born near the lateral ventricle migrate radially to reach their final positions to form the cortical plate. During this process, dynamic changes are observed in the morphologies and migration modes, including multipolar migration, locomotion, and terminal translocation, of the newborn neurons. Disruption of these migration processes can result in neuronal disorders such as lissencephaly and periventricular heterotopia. The extracellular protein, Reelin, mainly secreted by the Cajal-Retzius neurons in the marginal zone during development, plays a crucial role in the neuronal migration and neocortical lamination. Reelin signaling, which exerts essential roles in the formation of the layered neocortex, is triggered by the binding of Reelin to its receptors, ApoER2 and VLDLR, followed by phosphorylation of the Dab1 adaptor protein. Accumulating evidence suggests that Reelin signaling controls multiple steps of neuronal migration, including the transition from multipolar to bipolar neurons, terminal translocation, and termination of migration beneath the marginal zone. In addition, it has been shown that ectopically expressed Reelin can cause neuronal aggregation via an N-cadherin-mediated manner. This review attempts to summarize our knowledge of the roles played by Reelin in neuronal migration and the underlying mechanisms.
PubMed: 28507985
DOI: 10.3389/fcell.2017.00040 -
Developmental Neurobiology Jun 2011Drosophila neurons have identifiable axons and dendrites based on cell shape, but it is only just starting to become clear how Drosophila neurons are polarized at the... (Review)
Review
Drosophila neurons have identifiable axons and dendrites based on cell shape, but it is only just starting to become clear how Drosophila neurons are polarized at the molecular level. Dendrite-specific components including the Golgi complex, GABA receptors, neurotransmitter receptor scaffolding proteins, and cell adhesion molecules have been described. Proteins involved in constructing presynaptic specializations are concentrated in axons of some neurons. A very simple model for how these components are distributed to axons and dendrites can be constructed based on the opposite polarity of microtubules in axons and dendrites: dynein carries cargo into dendrites, and kinesins carry cargo into axons. The simple model works well for multipolar neurons, but will likely need refinement for unipolar neurons, which are common in Drosophila.
Topics: Animals; Axons; Cell Polarity; Dendrites; Drosophila; Neurons
PubMed: 21557498
DOI: 10.1002/dneu.20836 -
Molecular Neurobiology Sep 2022Changes in the transcription factor (TF) expression are critical for brain development, and they may also underlie neurodevelopmental disorders. Indeed, T-box brain1...
Changes in the transcription factor (TF) expression are critical for brain development, and they may also underlie neurodevelopmental disorders. Indeed, T-box brain1 (Tbr1) is a TF crucial for the formation of neocortical layer VI, and mutations and microdeletions in that gene are associated with malformations in the human cerebral cortex, alterations that accompany autism spectrum disorder (ASD). Interestingly, Tbr1 upregulation has also been related to the occurrence of ASD-like symptoms, although limited studies have addressed the effect of increased Tbr1 levels during neocortical development. Here, we analysed the impact of Tbr1 misexpression in mouse neural progenitor cells (NPCs) at embryonic day 14.5 (E14.5), when they mainly generate neuronal layers II-IV. By E18.5, cells accumulated in the intermediate zone and in the deep cortical layers, whereas they became less abundant in the upper cortical layers. In accordance with this, the proportion of Sox5 cells in layers V-VI increased, while that of Cux1 cells in layers II-IV decreased. On postnatal day 7, fewer defects in migration were evident, although a higher proportion of Sox5 cells were seen in the upper and deep layers. The abnormal neuronal migration could be partially due to the altered multipolar-bipolar neuron morphologies induced by Tbr1 misexpression, which also reduced dendrite growth and branching, and disrupted the corpus callosum. Our results indicate that Tbr1 misexpression in cortical NPCs delays or disrupts neuronal migration, neuronal specification, dendrite development and the formation of the callosal tract. Hence, genetic changes that provoke ectopic Tbr1 upregulation during development could provoke cortical brain malformations.
Topics: Animals; Autism Spectrum Disorder; Cerebral Cortex; Humans; Mice; Neocortex; Neurogenesis; Neurons; T-Box Domain Proteins; Transcription Factors
PubMed: 35781633
DOI: 10.1007/s12035-022-02936-x -
Frontiers in Neuroanatomy 2014The claustrum is a telencephalic structure which consists of dorsal segment adjoining the insular cortex and a ventral segment termed also endopiriform nucleus (END)....
The claustrum is a telencephalic structure which consists of dorsal segment adjoining the insular cortex and a ventral segment termed also endopiriform nucleus (END). The dorsal segment (claustrum) is divided into a dorsal and ventral zone, while the END is parcellated into dorsal, ventral and intermediate END. The claustrum and the END consist of glutamatergic projection neurons and GABAergic local interneurons coexpressing calcium binding proteins. Among neurons expressing calcium binding proteins the calretinin (CR)-immunoreactive interneurons exert specific functions in neuronal circuits, including disinhibition of excitatory neurons. Previous anatomical data indicate extensive and reciprocally organized claustral projections with cerebral cortex. We asked if the distribution of cells immunoreactive for CR delineates anatomical or functional subdivisions in the claustrum and in the END. Both segments of the claustrum and all subdivisions of the END contained CR immunoreactive neurons with varying distribution. The ventral zone of the claustrum exhibited weak labeling with isolated cell bodies and thin fibers and is devoid of immunoreactive puncta. Within the medial margin of the intermediate END we noted a group of strongly positive neurons. Cells immunoreactive for CR in all subdivisions of the claustrum and END were bipolar, multipolar and oval with smooth, beaded aspiny dendrites. Small number of CR-immunoreactive neurons displayed thin dendrites which enter to adjoining structures. Penetration of dendrites was reciprocal. These results show an inhomogenity over the claustrum and the END in distribution and types of CR immunoreactive neurons. The distribution of the CR-immunoreactive neurons respects the anatomical but not functional zones of the claustral complex.
PubMed: 25653596
DOI: 10.3389/fnana.2014.00160