Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

Science Advances, Journal Year: 2020, Volume and Issue: 6(31)

Published: July 24, 2020

Abstract: Altered olfactory function is a common symptom of COVID-19, but its etiology unknown. A key question whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 affects olfaction directly, by infecting sensory neurons or their targets bulb, indirectly, through perturbation supporting cells. Here we identify cell types epithelium and bulb that express entry molecules. Bulk sequencing demonstrated mouse, non-human primate human mucosa expresses two genes involved CoV-2 entry, ACE2 TMPRSS2. However, single revealed expressed support cells, stem perivascular rather than neurons. Immunostaining confirmed these results pervasive expression protein dorsally-located epithelial sustentacular cells pericytes mouse. These findings suggest infection non-neuronal leads to anosmia related disturbances odor perception patients.

Language: Английский

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Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain

Development, Journal Year: 2019, Volume and Issue: 146(4)

Published: Feb. 15, 2019

ABSTRACT In the adult rodent brain, neural stem cells (NSCs) persist in ventricular-subventricular zone (V-SVZ) and subgranular (SGZ), which are specialized niches young neurons for olfactory bulb (OB) hippocampus, respectively, generated. Recent studies have significantly modified earlier views on mechanisms of NSC self-renewal neurogenesis brain. Here, we discuss molecular control, heterogeneity, regional specification cell division modes V-SVZ NSCs, draw comparisons with NSCs SGZ. We highlight how regulated by local signals from their immediate neighbors, as well neurotransmitters factors that secreted distant neurons, choroid plexus vasculature. also review recent advances single RNA analyses reveal complexity neurogenesis. These findings set stage a better understanding neurogenesis, process one day may inspire new approaches to brain repair.

Language: Английский

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Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: March 27, 2020

Abstract Altered olfactory function is a common symptom of COVID-19, but its etiology unknown. A key question whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 affects olfaction directly by infecting sensory neurons or their targets bulb, indirectly, through perturbation supporting cells. Here we identify cell types epithelium and bulb that express entry molecules. Bulk sequencing revealed mouse, non-human primate human mucosa expresses two genes involved CoV-2 entry, ACE2 TMPRSS2. However, single immunostaining demonstrated expression support cells, stem perivascular cells; contrast, both did not message protein. These findings suggest infection non-neuronal leads to anosmia related disturbances odor perception patients.

Language: Английский

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Development of the mammalian main olfactory bulb

Development, Journal Year: 2022, Volume and Issue: 149(3)

Published: Feb. 1, 2022

ABSTRACT The mammalian main olfactory bulb is a crucial processing centre for the sense of smell. forms early during development and functional from birth. However, system continues to mature change throughout life as target constitutive adult neurogenesis. Our Review synthesises current knowledge prenatal, postnatal development, focusing on maturation, morphology, functions interactions its diverse constituent glutamatergic GABAergic cell types. We highlight not only great advances in understanding made recent years, but also gaps our present that most urgently require addressing.

Language: Английский

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A GnRH neuronal population in the olfactory bulb translates socially relevant odors into reproductive behavior in male mice

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(9), P. 1758 - 1773

Published: Aug. 2, 2024

Language: Английский

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Regulation of neurogenesis in the adult and aging brain

Current Opinion in Neurobiology, Journal Year: 2018, Volume and Issue: 53, P. 131 - 138

Published: Aug. 2, 2018

Neural stem cells (NSCs) represent a remarkable developmental unit, necessary for the proper functioning of neurogenesis, by retaining their plasticity to self-renew and give rise progeny throughout life in specific regions adult brain. Although NSCs were thought merely cell type brain, recent advances have demonstrated incredible complexity NSC identity functions. Ranging between quiescence, activation intermediary subtypes, choose fate through inheritance, regional positioning within niche, as well dynamic transcriptional metabolic states. The program is reflected tremendous changes they undergo upon external environmental cues extrinsic manipulations, harnessing these potentials can open new avenues fight against brain injury, neurodegenerative age-related diseases.

Language: Английский

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The choroid plexus maintains adult brain ventricles and subventricular zone neuroblast pool, which facilitates poststroke neurogenesis

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(28)

Published: July 2, 2024

The brain’s neuroreparative capacity after injuries such as ischemic stroke is partly contained in the neurogenic niches, primarily subventricular zone (SVZ), which lies close contact with cerebrospinal fluid (CSF) produced by choroid plexus (ChP). Despite wide range of their proposed functions, ChP/CSF remain among most understudied compartments central nervous system (CNS). Here, we report a mouse genetic tool (the ROSA26iDTR line) for noninvasive, specific, and temporally controllable ablation CSF-producing ChP epithelial cells to assess roles CSF brain homeostasis injury. Using this model, demonstrate that causes rapid permanent volume loss both aged young adult brains, accompanied disruption ependymal cilia bundles. Surprisingly, did not result overt neurological deficits at 1 mo postablation. However, observed pronounced decrease pool SVZ neuroblasts (NBs) following ablation, occurs due enhanced migration into olfactory bulb. In middle cerebral artery occlusion model stroke, NB lesion site was also reduced CSF-depleted mice. Thus, our study establishes an important role regulating regenerative under normal conditions stroke.

Language: Английский

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Embryonic and postnatal neurogenesis produce functionally distinct subclasses of dopaminergic neuron

eLife, Journal Year: 2018, Volume and Issue: 7

Published: April 19, 2018

Most neurogenesis in the mammalian brain is completed embryonically, but certain areas production of neurons continues throughout postnatal life. The functional properties mature postnatally generated often match those their embryonically produced counterparts. However, we show here that olfactory bulb (OB), embryonic and produce functionally distinct subpopulations dopaminergic (DA) neurons. We define two subclasses OB DA neuron by presence or absence a key subcellular specialisation: axon initial segment (AIS). Large AIS-positive axon-bearing are exclusively during early stages, leaving small anaxonic AIS-negative cells as only subtype via adult neurogenesis. These populations distinct: large more excitable, yet display weaker – for long-latency inhibitory events broadly tuned responses to odorant stimuli. Embryonic can therefore generate neuronal subclasses, placing important constraints on roles adult-born sensory processing.

Language: Английский

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Diversity of Axonal and Dendritic Contributions to Neuronal Output

Frontiers in Cellular Neuroscience, Journal Year: 2020, Volume and Issue: 13

Published: Jan. 22, 2020

Our general understanding of neuronal function is that dendrites receive information transmitted to the axon, where action potentials are initiated and propagated eventually trigger neurotransmitter release at synaptic terminals. Even though this canonical division labor true for a number types in mammalian brain (including neocortical hippocampal pyramidal neurons or cerebellar Purkinje neurons), many do not comply with classical polarity scheme. In fact can be site potential initiation propagation, even release. several interneuron types, all functions carried out by as these devoid axon. article, we present few examples "misbehaving" (with non-canonical scheme) highlight diversity solutions used transmit information. Moreover, discuss how contribution axons excitability may impose constraints on morphology compartments specific functional contexts.

Language: Английский

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Brief Sensory Deprivation Triggers Cell Type-Specific Structural and Functional Plasticity in Olfactory Bulb Neurons

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(10), P. 2135 - 2151

Published: Jan. 22, 2021

Can alterations in experience trigger different plastic modifications neuronal structure and function, if so, how do they integrate at the cellular level? To address this question, we interrogated circuitry mouse olfactory bulb responsible for earliest steps odor processing. We induced experience-dependent plasticity mice of either sex by blocking one nostril day, a minimally invasive manipulation that leaves sensory organ undamaged is akin to natural transient blockage suffered during common mild rhinal infections. found such brief deprivation produced structural functional highly specialized bulbar cell type: axon-bearing dopaminergic neurons glomerular layer. After 24 h naris occlusion, axon initial segment (AIS) became significantly shorter, modification was also associated with decrease intrinsic excitability. These effects were specific AIS-positive subpopulation because no excitability observed AIS-negative cells. Moreover, occlusion changes AIS excitatory neurons, mitral/tufted external tufted cells, nor did it alter their By targeting subpopulation, early networks might act fine-tune processing face continually fluctuating inputs. SIGNIFICANCE STATEMENT Sensory need be so can adapt incoming stimuli. see cells circuits change response challenges, blocked just naturally relevant occurs cold. induces forms axonal subtype: interneurons. In contrast, properties axon-lacking neighboring remained unchanged. Within same circuits, types therefore make distinct an ever-changing landscape.

Language: Английский

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