-
Current Neuropharmacology 2018Accumulating evidence has shown the importance of glial cells in the neurobiology of bipolar disorder. Activated microglia and inflammatory cytokines have been pointed... (Review)
Review
Accumulating evidence has shown the importance of glial cells in the neurobiology of bipolar disorder. Activated microglia and inflammatory cytokines have been pointed out as potential biomarkers of bipolar disorder. Indeed, recent studies have shown that bipolar disorder involves microglial activation in the hippocampus and alterations in peripheral cytokines, suggesting a potential link between neuroinflammation and peripheral toxicity. These abnormalities may also be the biological underpinnings of outcomes related to neuroprogression, such as cognitive impairment and brain changes. Additionally, astrocytes may have a role in the progression of bipolar disorder, as these cells amplify inflammatory response and maintain glutamate homeostasis, preventing excitotoxicity. The present review aims to discuss neuron-glia interactions and their role in the pathophysiology and treatment of bipolar disorder.
Topics: Animals; Bipolar Disorder; Cell Communication; Cytokines; Humans; Neuroglia; Neurons
PubMed: 28847296
DOI: 10.2174/1570159X15666170828170921 -
Neuron Oct 2012The mammalian retina consists of neurons of >60 distinct types, each playing a specific role in processing visual images. They are arranged in three main stages. The... (Review)
Review
The mammalian retina consists of neurons of >60 distinct types, each playing a specific role in processing visual images. They are arranged in three main stages. The first decomposes the outputs of the rod and cone photoreceptors into ∼12 parallel information streams. The second connects these streams to specific types of retinal ganglion cells. The third combines bipolar and amacrine cell activity to create the diverse encodings of the visual world--roughly 20 of them--that the retina transmits to the brain. New transformations of the visual input continue to be found: at least half of the encodings sent to the brain (ganglion cell response selectivities) remain to be discovered. This diversity of the retina's outputs has yet to be incorporated into our understanding of higher visual function.
Topics: Animals; Humans; Nerve Net; Neurons; Retina; Visual Pathways
PubMed: 23083731
DOI: 10.1016/j.neuron.2012.10.002 -
Bio Systems Jun 2022Instead of the conventional 0 and 1 values, bipolar reasoning uses -1, 0, +1 to describe double-sided judgements in which neutral elements are halfway between positive...
Instead of the conventional 0 and 1 values, bipolar reasoning uses -1, 0, +1 to describe double-sided judgements in which neutral elements are halfway between positive and negative evaluations (e.g., "uncertain" lies between "impossible" and "totally sure"). We discuss the state-of-the-art in bipolar logics and recall two medieval forerunners, i.e., William of Ockham and Nicholas of Autrecourt, who embodied a bipolar mode of thought that is eminently modern. Starting from the trivial observation that "once a wheat sheaf is sealed and tied up, the packed down straws display the same orientation", we work up a new theory of the bipolar nature of networks, suggesting that orthodromic (i.e., feedforward, bottom-up) projections might be functionally coupled with antidromic (i.e., feedback, top-down) projections via the mathematical apparatus of presheaves/globular sets. When an entrained oscillation such as a neuronal spike propagates from A to B, changes in B might lead to changes in A, providing unexpected antidromic effects. Our account points towards the methodological feasibility of novel neural networks in which message feedback is guaranteed by backpropagation mechanisms endowed in the same feedforward circuits. Bottom-up/top-down transmission at various coarse-grained network levels provides fresh insights in far-flung scientific fields such as object persistence, memory reinforcement, visual recognition, Bayesian inferential circuits and multidimensional activity of the brain. Implying that axonal stimulation by external sources might backpropagate and modify neuronal electric oscillations, our theory also suggests testable previsions concerning the optimal location of transcranial magnetic stimulation's coils in patients affected by drug-resistant epilepsy.
Topics: Humans; Bayes Theorem; Feedback; Neural Networks, Computer; Neurons
PubMed: 35247481
DOI: 10.1016/j.biosystems.2022.104652 -
Development (Cambridge, England) Jun 2015Neurons are highly polarized cells with structurally and functionally distinct processes called axons and dendrites. This polarization underlies the directional flow of... (Review)
Review
Neurons are highly polarized cells with structurally and functionally distinct processes called axons and dendrites. This polarization underlies the directional flow of information in the central nervous system, so the establishment and maintenance of neuronal polarization is crucial for correct development and function. Great progress in our understanding of how neurons establish their polarity has been made through the use of cultured hippocampal neurons, while recent technological advances have enabled in vivo analysis of axon specification and elongation. This short review and accompanying poster highlight recent advances in this fascinating field, with an emphasis on the signaling mechanisms underlying axon and dendrite specification in vitro and in vivo.
Topics: Animals; Axons; Brain; Cell Polarity; Dendrites; Humans; Mice; Neurons; Signal Transduction; rho GTP-Binding Proteins
PubMed: 26081570
DOI: 10.1242/dev.114454 -
Revista de Psiquiatria Y Salud Mental 2012Bipolar disorder, like the majority of psychiatric disorders, is considered a neurodevelopment disease of neurodevelopment. There is an increased rate of neuronal birth... (Review)
Review
Bipolar disorder, like the majority of psychiatric disorders, is considered a neurodevelopment disease of neurodevelopment. There is an increased rate of neuronal birth and death during this development period. In the particular case of the processes that determine neuronal death, it is known that those neurons that establish connections have to be removed from the central nervous system. There is a deficit of GABAergic interneurons in the cerebral cortex in bipolar disorder, accompanied by overexpression of proapoptic genes. There is also an alteration in the expression of molecules that mediate in the migration of these neurons and their inclusion in functional synapsis during the foetal stage. The role of these molecules in the neuronal death pathways by apoptosis will be reviewed here in an attempt to establish biological hypotheses of the genesis of bipolar disorder.
Topics: Apoptosis; Bipolar Disorder; Cell Movement; Humans; Neurons; Synaptic Transmission
PubMed: 22854584
DOI: 10.1016/j.rpsm.2011.11.005 -
Nature Dec 2023The basic plan of the retina is conserved across vertebrates, yet species differ profoundly in their visual needs. Retinal cell types may have evolved to accommodate... (Comparative Study)
Comparative Study
The basic plan of the retina is conserved across vertebrates, yet species differ profoundly in their visual needs. Retinal cell types may have evolved to accommodate these varied needs, but this has not been systematically studied. Here we generated and integrated single-cell transcriptomic atlases of the retina from 17 species: humans, two non-human primates, four rodents, three ungulates, opossum, ferret, tree shrew, a bird, a reptile, a teleost fish and a lamprey. We found high molecular conservation of the six retinal cell classes (photoreceptors, horizontal cells, bipolar cells, amacrine cells, retinal ganglion cells (RGCs) and Müller glia), with transcriptomic variation across species related to evolutionary distance. Major subclasses were also conserved, whereas variation among cell types within classes or subclasses was more pronounced. However, an integrative analysis revealed that numerous cell types are shared across species, based on conserved gene expression programmes that are likely to trace back to an early ancestral vertebrate. The degree of variation among cell types increased from the outer retina (photoreceptors) to the inner retina (RGCs), suggesting that evolution acts preferentially to shape the retinal output. Finally, we identified rodent orthologues of midget RGCs, which comprise more than 80% of RGCs in the human retina, subserve high-acuity vision, and were previously believed to be restricted to primates. By contrast, the mouse orthologues have large receptive fields and comprise around 2% of mouse RGCs. Projections of both primate and mouse orthologous types are overrepresented in the thalamus, which supplies the primary visual cortex. We suggest that midget RGCs are not primate innovations, but are descendants of evolutionarily ancient types that decreased in size and increased in number as primates evolved, thereby facilitating high visual acuity and increased cortical processing of visual information.
Topics: Animals; Humans; Neurons; Retina; Retinal Ganglion Cells; Single-Cell Gene Expression Analysis; Vertebrates; Vision, Ocular; Species Specificity; Biological Evolution; Amacrine Cells; Photoreceptor Cells; Ependymoglial Cells; Retinal Bipolar Cells; Visual Perception
PubMed: 38092908
DOI: 10.1038/s41586-023-06638-9 -
Biological Psychiatry Sep 2000The literature on the neuropathology of bipolar disorder (BD) is reviewed. Postmortem findings in the areas of pathomorphology, signal transduction, neuropeptides,... (Review)
Review
The literature on the neuropathology of bipolar disorder (BD) is reviewed. Postmortem findings in the areas of pathomorphology, signal transduction, neuropeptides, neurotransmitters, cell adhesion molecules, and synaptic proteins are considered. Decreased glial numbers and density in both BD and major depressive disorder (MDD) have been reported, whereas cortical neuron counts were not different in BD (in Brodmann's areas [BAs] 9 and 24). In contrast, MDD patients showed reductions in neuronal size and density (BA 9, BA 47). There are a number of findings of alterations in neuropeptides and monoamines in BD brains. Norepinephrine turnover was increased in several cortical regions and thalamus, whereas the serotonin metabolite, 5-hydroxyindoleacetic acid, and the serotonin transporter were reduced in the cortex. Several reports further implicated both cyclic adenosine monophosphate and phosphatidylinositol (PI) cascade abnormalities. G protein concentrations and activity increases were found in the occipital, prefrontal, and temporal cortices in BD. In the PI signal cascade, alterations in PKC activity were found in the prefrontal cortex. In the occipital cortex, PI hydrolysis was decreased. Two isoforms of the neural cell adhesion molecules were increased in the hippocampus of BD, whereas the synaptic protein marker, synaptophysin, was not changed. The findings of glial reduction, excess signal activity, neuropeptide abnormalities, and monoamine alterations suggest distinct imbalances in neurochemical regulation. Possible alterations in pathways involving ascending projections from the brain stem are considered. Larger numbers of BD brains are needed to further refine the conceptual models that have been proposed, and to develop coherent models of the pathophysiology of BD.
Topics: Autopsy; Bipolar Disorder; Brain; Brain Chemistry; Cell Adhesion Molecules; Humans; Nerve Tissue Proteins; Neuroglia; Neurons; Signal Transduction
PubMed: 11018222
DOI: 10.1016/s0006-3223(00)00978-1 -
Bipolar Disorders Mar 2019This limited review examines the role of the reticular activating system (RAS), especially the pedunculopontine nucleus (PPN), one site of origin of bottom-up gamma, in... (Review)
Review
OBJECTIVES
This limited review examines the role of the reticular activating system (RAS), especially the pedunculopontine nucleus (PPN), one site of origin of bottom-up gamma, in the symptoms of bipolar disorder (BD).
METHODS
The expression of neuronal calcium sensor protein 1 (NCS-1) in the brains of BD patients is increased. It has recently been found that all PPN neurons manifest intrinsic membrane beta/gamma frequency oscillations mediated by high threshold calcium channels, suggesting that it is one source of bottom-up gamma. This review specifically addresses the involvement of these channels in the manifestation of BD.
RESULTS
Excess NCS-1 was found to dampen gamma band oscillations in PPN neurons. Lithium, a first line treatment for BD, was found to decrease the effects of NCS-1 on gamma band oscillations in PPN neurons. Moreover, gamma band oscillations appear to epigenetically modulate gene transcription in PPN neurons, providing a new direction for research in BD.
CONCLUSIONS
This is an area needing much additional research, especially since the dysregulation of calcium channels may help explain many of the disorders of arousal in, elicit unwanted neuroepigenetic modulation in, and point to novel therapeutic avenues for, BD.
Topics: Animals; Bipolar Disorder; Calcium Channels; Epigenesis, Genetic; Gamma Rhythm; Humans; Neuronal Calcium-Sensor Proteins; Neurons; Neuropeptides; Pedunculopontine Tegmental Nucleus
PubMed: 30506611
DOI: 10.1111/bdi.12735 -
Vision Research Dec 1993The b-wave of the electroretinogram (ERG) is believed to result largely from the light responses of ON bipolar neurons. One apparent inconsistency is that the b-wave is... (Comparative Study)
Comparative Study
The b-wave of the electroretinogram (ERG) is believed to result largely from the light responses of ON bipolar neurons. One apparent inconsistency is that the b-wave is a phasic signal, more similar to ON responses of transient third-order neurons than to the ON bipolar light responses. However, when selective glutamate agonists or antagonists were used to isolate the b-wave, it was found to be tonic and resemble the light response waveform of the ON bipolar cell.
Topics: Ambystoma; Aminobutyrates; Animals; Electroretinography; In Vitro Techniques; Neurons; Photic Stimulation; Retina
PubMed: 8249322
DOI: 10.1016/0042-6989(93)90122-d -
International Review of Cell and... 2018During fetal and postnatal development, the human brain generates 160 billion neuronal and glial cells, each with precise cellular phenotypes. To effectively manage such... (Review)
Review
During fetal and postnatal development, the human brain generates 160 billion neuronal and glial cells, each with precise cellular phenotypes. To effectively manage such a complicated task, intrinsic (e.g., transcription factors) and extrinsic (environmental signals) cues cooperate to regulate the decision by neural progenitors to continue to proliferate or to differentiate. Loss- and gain-of-function studies in the mouse brain have been instrumental in identifying these cues, leading to a fairly well-developed and well-integrated model of neocortical development. This research has revealed that the neurons, astrocytes, and oligodendrocytes that populate the mature neocortex are generated sequentially from neural progenitor pools in both the dorsal (pallial) and ventral (subpallial) telencephalon. Understanding how cellular diversity is established during neocortical development is critical, as appropriate numbers of inhibitory and excitatory neurons, oligodendrocytes, and astrocytes are required for normal neural function. Indeed, an imbalance in excitatory vs inhibitory neurotransmission or alterations in glial cell number are hallmark features of neuropsychological and intellectual disorders such as schizophrenia, bipolar disorder, and autism. Moreover, these fundamental studies are beginning to pave the way for the rational design of neural cell reprogramming strategies, which are of value for the assessment of disease etiology, and for the possible development of novel cell-based therapies. We review herein our current understanding of the intrinsic cues and environmental signals that govern cell fate specification and differentiation decisions during development of neuronal and glial lineages in the murine neocortex.
Topics: Animals; Cell Differentiation; Cerebral Cortex; Humans; Neurogenesis; Neurons
PubMed: 29413892
DOI: 10.1016/bs.ircmb.2017.07.005