Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers, FGF22 and FGF7

Terauchi, Akiko; Timmons, Kendall M.; Kikuma, Koto; Pechmann, Yvonne; Kneussel, Matthias; Umemori, Hisashi

doi:10.1242/jcs.158337

Cited by 25 publications

(24 citation statements)

References 63 publications

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“…Finally, excitatory synaptic activity is known to induce rapidly the mobility of SAP102 in dendritic spines [78]. This protein plays a key role in the synaptic clearance of NMDAR [79] and is one of those involved in the regulation of inhibitory synapse formation by excitatory synaptic activity [80]. Interestingly, we observed a higher level of soluble SAP102 in transgenic animals of both sexes, confirming that brain hyperactivity found in 3xTg-AD mice impacted SAP102.…”

Section: Physiological Changes Induced By Transgene Expression In Botsupporting

confidence: 80%

Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice

Arsenault

Tremblay

Émond

2020

Preprint

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While the higher prevalence of Alzheimer Disease (AD) is clear, studies suggest that biological sex may also influence its pathogenesis . However, mechanisms behind these differences are not clear. To investigate physiological differences between sexes at the cellular level in the brain, we investigated the intrinsic and synaptic properties of entorhinal cortex neurons in heterozygous 3xTg-AD mice of both sexes at the age of 20 months. This brain region was selected because of its early association with AD symptoms . First, we found physiological differences between male and female non-transgenic mice, providing indirect evidence of axonal alterations in old females. Second, we observed a transgene-dependent elevation of the firing activity, post-burst after hyperpolarization (AHP) and spontaneous excitatory postsynaptic current (EPSC) activity, without any effect of sex. Third, the passive properties and the hyperpolarization-activated current (Ih) were altered by transgene expression only in female mice, whereas paired-pulse ratio (PPR) of evoked EPSC was changed only in males. Fourth, both sex and transgene expression were associated with changes in action potential properties. Consistent with previous work, higher levels of Aβ neuropathology were detected in 3xTg-AD females, whereas tau deposition was similar . In summary, our results support the idea that aging and AD neuropathology differentially alter the physiology of entorhinal cortex neurons in males and females.

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Section: Physiological Changes Induced By Transgene Expression In Botsupporting

confidence: 80%

Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice

Arsenault

Tremblay

Émond

2020

Preprint

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“…The most upregulated DEGs at 14 dpi are PRG4 (FC of 10) and FILIP1 (FC of 7), important for myelination and neuron migration; fibroblast growth factor 7 (FGF7, FC of 7), which regulates balance between excitatory and inhibitory synapse signaling in neurons (96); and NIMA-related kinase 1 (NEK1, FC of 5), which plays a role in axon development (97). The 509 DEGs downregulated at 14 dpi enriched to GO terms associated with signaling and nervous system development ( Table 2).…”

Section: Fig 7 Immunohistochemistry Gene Validation Ihc Staining Andmentioning

confidence: 99%

Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

Arnold

Girke

Sureshchandra

et al. 2016

J Virol

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Primary infection with varicella-zoster virus (VZV), a neurotropic alphaherpesvirus, results in varicella. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. The relationship between VZV and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. Intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV) recapitulates the hallmarks of VZV infection in humans. We leveraged this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes on days postinfection (dpi) 3, 7, 10, 14, and 100. SVV DNA and transcripts were detected in sensory ganglia 3 dpi, before the appearance of rash. CD4 and CD8 T cells were also detected in the sensory ganglia 3 dpi. Moreover, lung-resident T cells isolated from the same animals 3 dpi also harbored SVV DNA and transcripts, suggesting that T cells may be responsible for trafficking SVV to the ganglia. Transcriptome sequencing (RNA-Seq) analysis showed that cessation of viral transcription 7 dpi coincides with a robust antiviral innate immune response in the ganglia. Interestingly, a significant number of genes that play a critical role in nervous system development and function remained downregulated into latency. These studies provide novel insights into host-pathogen interactions in the sensory ganglia during acute varicella and demonstrate that SVV infection results in profound and sustained changes in neuronal gene expression. IMPORTANCEMany aspects of VZV infection of sensory ganglia remain poorly understood, due to limited access to human specimens and the fact that VZV is strictly a human virus. Infection of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, provides a robust model of the human disease. Using this model, we show that SVV reaches the ganglia early after infection, most likely by T cells, and that the induction of a robust innate immune response correlates with cessation of virus transcription. We also report significant changes in the expression of genes that play an important role in neuronal function. Importantly, these changes persist long after viral replication ceases. Given the homology between SVV and VZV, and the genetic and physiological similarities between rhesus macaques and humans, our results provide novel insight into the interactions between VZV and its human host and explain some of the neurological consequences of VZV infection. V aricella-zoster virus (VZV) is a neurotropic alphaherpesvirus and the causative agent of varicella (chickenpox) (1). VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster (shingles), a painful disease that affects almost 1 million individuals in the United States alone (2). VZV is transmitted through the inhalation of virus-laden saliva droplets or by direct contact with the infectious fluid from vesicles...

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“…Actually, FGF22 and FGF7 anterograde trafficking is mediated by different motors and it occurs in association with excitatory or inhibitory postsynaptic density proteins, respectively (Terauchi et al . ). Astrocytes also have the ability of selectively boosting inhibitory synaptogenesis (Hughes et al .…”

Section: Presynaptic Differentiationmentioning

confidence: 97%

Puzzling out presynaptic differentiation

Pinto

Almeida

2016

Journal of Neurochemistry

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Proper brain function in the nervous system relies on the accurate establishment of synaptic contacts during development. Countless synapses populate the adult brain in an orderly fashion. In each synapse, a presynaptic terminal loaded with neurotransmitters-containing synaptic vesicles is perfectly aligned to an array of receptors in the postsynaptic membrane. Presynaptic differentiation, which encompasses the events underlying assembly of new presynaptic units, has seen notable advances in recent years. It is now consensual that as a growing axon encounters the receptive dendrites of its partner, presynaptic assembly will be triggered and specified by multiple postsynaptically-derived factors including soluble molecules and cell adhesion complexes. Presynaptic material that reaches these distant sites by axonal transport in the form of pre-assembled packets will be retained and clustered, ultimately giving rise to a presynaptic bouton. This review focuses on the cellular and molecular aspects of presynaptic differentiation in the central nervous system, with a particular emphasis on the identity of the instructive factors and the intracellular processes used by neuronal cells to assemble functional presynaptic terminals.

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Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers, FGF22 and FGF7

Cited by 25 publications

References 63 publications

Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice

Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice

Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

Puzzling out presynaptic differentiation

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