Cerebellin 4, a synaptic protein, enhances inhibitory activity and resistance of neurons to amyloid-β toxicity

Chacón, Pedro; Marco, Angel Del; Arévalo, Ángeles; Domínguez-Giménez, Paloma; García‐Segura, Luis M.; Rodríguez‐Tébar, Alfredo

doi:10.1016/j.neurobiolaging.2014.11.006

Cited by 22 publications

(19 citation statements)

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“…We identified 19 cell-type-enriched LRGs (of 55 LRGs induced in excitatory neurons), including several secreted modulators of synaptic plasticity 15 . For example, Cerebellin 4 ( Cbln4 ), which encodes a secreted factor implicated in inhibitory synapse recruitment 27 , was enriched in layer 4 excitatory neurons, which we confirmed by FISH ( Fig. 4a ).…”

Section: Resultssupporting

confidence: 66%

Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex

et al. 2017

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Activity-dependent transcriptional responses shape cortical function. However, we lack a comprehensive understanding of the diversity of these responses across the full range of cortical cell types, and how these changes contribute to neuronal plasticity and disease. Here we applied high-throughput single-cell RNA-sequencing to investigate the breadth of transcriptional changes that occur across cell types in mouse visual cortex following exposure to light. We identified significant and divergent transcriptional responses to stimulation in each of the 30 cell types characterized, revealing 611 stimulus-responsive genes. Excitatory pyramidal neurons exhibit inter- and intra-laminar heterogeneity in the induction of stimulus responsive genes. Non-neuronal cells demonstrated clear transcriptional responses that may regulate experience-dependent changes in neurovascular coupling and myelination. Together, these results reveal the dynamic landscape of stimulus-dependent transcriptional changes that occur across cell types in visual cortex, which are likely critical for cortical function and may be sites of de-regulation in developmental brain disorders.

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Section: Resultssupporting

confidence: 66%

Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex

et al. 2017

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“…The SZ-DMPs discovered in this study include genes important in neuronal function (eg, NCOR2 , SULT4A1 , and HES1 ), genes previously associated with SZ (eg, RPS6KA1 , MAD1L1 , and DDR1 ), and genes also involved in T-cell development ( ZC3H12D , TCF3 , and IKZF4 ). Several of the neuronal genes have been implicated in Alzheimer disease pathology ( SORL1 , 57 HES1 , 58 MARK4 , 59 SCAP , 60 DHCR24 , 61 GAS7 , 62 CARD10 , 63 CDC37 , 64 CUTA , 65 IRS1 , 66 and FOXO1 67 ), supporting a common network of dysregulation in SZ and Alzheimer disease. 68…”

Section: Discussionmentioning

confidence: 88%

Association of DNA Methylation Differences With Schizophrenia in an Epigenome-Wide Association Study

et al. 2016

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“…Notably, several neuropeptide genes that were strongly downregulated reduced appetite when injected in the lateral cerebral ventricle. For example, the neuropeptide CBLN4 strongly reduced food intake, and Cbln4 has been implicated in regulating inhibitory synapse function and is thought to play a neuroprotective role ( Chacon et al, 2015 ). In addition, PTN is an inhibitor of receptor tyrosine phosphatase β/ζ, and its reduction might reduce cytokine signaling through tyrosine kinase receptors, which include leptin and insulin receptors.…”

Section: Discussionmentioning

confidence: 99%

Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss

Henry

Sugino

Tozer

et al. 2015

eLife

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Molecular and cellular processes in neurons are critical for sensing and responding to energy deficit states, such as during weight-loss. Agouti related protein (AGRP)-expressing neurons are a key hypothalamic population that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss, and here we report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived young adult mice. For comparison, we also analyzed Proopiomelanocortin (POMC)-expressing neurons, an intermingled population that suppresses appetite and body weight. We find that AGRP neurons are considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion channels, neuropeptides, and receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders.DOI: http://dx.doi.org/10.7554/eLife.09800.001

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Cerebellin 4, a synaptic protein, enhances inhibitory activity and resistance of neurons to amyloid-β toxicity

Cited by 22 publications

References 50 publications

Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex

Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex

Association of DNA Methylation Differences With Schizophrenia in an Epigenome-Wide Association Study

Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss

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