Tuning Local Calcium Availability: Cell-Type-Specific Immobile Calcium Buffer Capacity in Hippocampal Neurons

Although mRNAs are localized in the processes of excitatory neurons, it is still unclear whether interneurons also localize a large population of mRNAs. In addition, the variability in the localized mRNA population within and between cell-types is unknown. Here we describe the unbiased transcriptomic characterization of the subcellular compartments of hundreds of single neurons. We separately profiled the dendritic and somatic transcriptomes of individual rat hippocampal neurons and investigated mRNA abundances in the soma and dendrites of single glutamatergic and GABAergic neurons. We found that, like their excitatory counterparts, interneurons contain a rich repertoire of ~4000 mRNAs. We observed more cell type-specific features among somatic transcriptomes than their associated dendritic transcriptomes. Finally, using cell-type specific metabolic labelling of isolated neurites, we demonstrated that the processes of Glutamatergic and, notably, GABAergic neurons were capable of local translation, suggesting mRNA localization and local translation is a general property of neurons.

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Concentration- and cell type-specific effects of calbindin D28k on vulnerability of hippocampal neurons to seizure-induced injury

Molecular Brain Research ◽

10.1016/s0169-328x(99)00299-5 ◽

2000 ◽

Vol 75 (1) ◽

pp. 89-95 ◽

Cited By ~ 29

Author(s):

Devin S Gary ◽

Karen Sooy ◽

Sic L Chan ◽

Sylvia Christakos ◽

Mark P Mattson

Keyword(s):

Hippocampal Neurons ◽

Cell Type ◽

Specific Effects ◽

Cell Type Specific ◽

Calbindin D28k

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Subcellular sequencing of single neurons reveals the dendritic transcriptome of GABAergic interneurons

10.1101/2020.10.17.341651 ◽

2020 ◽

Author(s):

Julio D. Perez ◽

Susanne tom Dieck ◽

Beatriz Alvarez-Castelao ◽

Ivy C.W. Chan ◽

Erin M. Schuman

Keyword(s):

Hippocampal Neurons ◽

Large Population ◽

Cell Types ◽

Gabaergic Neurons ◽

Gabaergic Interneurons ◽

Local Translation ◽

Cell Type ◽

Cell Type Specific ◽

The Individual

AbstractThe localization and translation of mRNAs to dendrites and axons maintains and modifies the local proteome of neurons, and is essential for synaptic plasticity. Although significant efforts have allowed the identification of localized mRNAs in excitatory neurons, it is still unclear whether interneurons also localize a large population of mRNAs. In addition, the variability in the population of localized mRNAs within and between cell-types is unknown. Here we developed a method for the transcriptomic characterization of a single neuron’s subcellular compartments, which combines laser capture microdissection with scRNA-seq. This allowed us to separately profile the dendritic and somatic transcriptomes of individual rat hippocampal neurons and investigate the relation in mRNA abundances between the soma and dendrites of single glutamatergic and GABAergic neurons. We identified two types of glutamatergic and three types of GABAergic interneurons and we found that, like their excitatory counterparts, interneurons contain a rich repertoire of ~4000 mRNAs. The individual somatic transcriptomes exhibited more cell type-specific features than their associated dendritic transcriptomes. The detection and abundance of dendritic mRNAs was not always simply predicted by their somatic counterparts. Finally, using cell-type specific metabolic labelling of isolated neurites, we demonstrated that the processes not only of Glutamatergic but also of GABAergic neurons are capable of local translation, suggesting mRNA localization and local translation is a general property of neurons.

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The Knockdown of TREK-1 in Hippocampal Neurons Attenuate Lipopolysaccharide-Induced Depressive-Like Behavior in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20235902 ◽

2019 ◽

Vol 20 (23) ◽

pp. 5902 ◽

Cited By ~ 3

Author(s):

Ajung Kim ◽

Hyun-Gug Jung ◽

Yeong-Eun Kim ◽

Seung-Chan Kim ◽

Jae-Yong Park ◽

...

Keyword(s):

Hippocampal Neurons ◽

Tail Suspension Test ◽

Gene Cassette ◽

Brain Diseases ◽

Cell Type ◽

Adeno Associated Virus ◽

Antidepressant Effects ◽

Cell Type Specific ◽

The Brain ◽

Lps Treatment

TWIK-related potassium channel-1 (TREK-1) is broadly expressed in the brain and involved in diverse brain diseases, such as seizures, ischemia, and depression. However, the cell type-specific roles of TREK-1 in the brain are largely unknown. Here, we generated a Cre-dependent TREK-1 knockdown (Cd-TREK-1 KD) transgenic mouse containing a gene cassette for Cre-dependent TREK-1 short hairpin ribonucleic acid to regulate the cell type-specific TREK-1 expression. We confirmed the knockdown of TREK-1 by injecting adeno-associated virus (AAV) expressing Cre into the hippocampus of the mice. To study the role of hippocampal neuronal TREK-1 in a lipopolysaccharide (LPS)-induced depression model, we injected AAV-hSyn-BFP (nCTL group) or AAV-hSyn-BFP-Cre (nCre group) virus into the hippocampus of Cd-TREK-1 KD mice. Interestingly, the immobility in the tail suspension test after LPS treatment did not change in the nCre group. Additionally, some neurotrophic factors (BDNF, VEGF, and IGF-1) significantly increased more in the nCre group compared to the nCTL group after LPS treatment, but there was no difference in the expression of their receptors. Therefore, our data suggest that TREK-1 in the hippocampal neurons has antidepressant effects, and that Cd-TREK-1 KD mice are a valuable tool to reveal the cell type-specific roles of TREK-1 in the brain.

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Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer’s Disease

Metabolites ◽

10.3390/metabo11090616 ◽

2021 ◽

Vol 11 (9) ◽

pp. 616

Author(s):

Kyoka Hoshi ◽

Hiromi Ito ◽

Eriko Abe ◽

Takashi J. Fuwa ◽

Mayumi Kanno ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hippocampal Neurons ◽

Neurological Diseases ◽

Ultra Performance Liquid Chromatography ◽

Cell Type ◽

Post Translational Modification ◽

A Cell ◽

Cell Type Specific ◽

The Brain

Glycosylation is a cell type-specific post-translational modification that can be used for biomarker identification in various diseases. Aim of this study is to explore glycan-biomarkers on transferrin (Tf) for Alzheimer’s disease (AD) in cerebrospinal fluid (CSF). Glycan structures of CSF Tf were analyzed by ultra-performance liquid chromatography followed by mass spectrometry. We found that a unique mannosylated-glycan is carried by a Tf isoform in CSF (Man-Tf). The cerebral cortex contained Man-Tf as a major isofom, suggesting that CSF Man-Tf is, at least partly, derived from the cortex. Man-Tf levels were analyzed in CSF of patients with neurological diseases. Concentrations of Man-Tf were significantly increased in AD and mild cognitive impairment (MCI) comparing with other neurological diseases, and the levels correlated well with those of phosphorylated-tau (p-tau), a representative AD marker. Consistent with the observation, p-tau and Tf were co-expressed in hippocampal neurons of AD, leading to the notion that a combined p-tau and Man-Tf measure could be a biomarker for AD. Indeed, levels of p-tau x Man-Tf showed high diagnostic accuracy for MCI and AD; 84% sensitivities and 90% specificities for MCI and 94% sensitivities and 89% specificities for AD. Thus Man-Tf could be a new biomarker for AD.

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