Calmodulin activity regulates group I metabotropic glutamate receptor‐mediated signal transduction and synaptic depression

Sethna, Ferzin; Zhang, Ming; Kaphzan, Hanoch; Klann, Eric; Autio, Dawn M.; Cox, Charles L.; Wang, Hongbing

doi:10.1002/jnr.23719

Cited by 10 publications

(6 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Excitotoxicity involving aberrant calcium ion binding is a main neuropathological process in various neurodegenerative disorders [ 55 ]. Calmodulin activity reportedly regulates group I metabotropic glutamate receptor-mediated signal transduction and synaptic depression [ 56 ]. The complement system plays an essential role in synaptic plasticity and cognitive functions [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Differentially Expressed Genes in the Dentate Gyrus and Anterior Cingulate Cortex in a Mouse Model of Depression

Wei

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

Major depressive disorder (MDD) is a prevalent, chronic, and relapse-prone psychiatric disease. However, the intermediate molecules resulting from stress and neurological impairment in different brain regions are still unclear. To clarify the pathological changes in the dentate gyrus (DG) and anterior cingulate cortex (ACC) regions of the MDD brain, which are the most closely related to the disease, we investigated the published microarray profile dataset GSE84183 to identify unpredictable chronic mild stress- (UCMS-) induced differentially expressed genes (DEGs) in the DG and ACC regions. Based on the DEG data, functional annotation, protein-protein interaction, and transcription factor (TF) analyses were performed. In this study, 1071 DEGs (679 upregulated and 392 downregulated) and 410 DEGs (222 upregulated and 188 downregulated) were identified in DG and ACC, respectively. The pathways and GO terms enriched by the DEGs in the DG, such as cell adhesion, proteolysis, ion transport, transmembrane transport, chemical synaptic transmission, immune system processes, response to lipopolysaccharide, and nervous system development, may reveal the molecular mechanism of MDD. However, the DEGs in the ACC involved metabolic processes, proteolysis, visual learning, DNA methylation, innate immune responses, cell migration, and circadian rhythm. Sixteen hub genes in the DG (Fn1, Col1a1, Anxa1, Penk, Ptgs2, Cdh1, Timp1, Vim, Rpl30, Rps21, Dntt, Ptk2b, Jun, Avp, Slit1, and Sema5a) were identified. Eight hub genes in the ACC (Prkcg, Grin1, Syngap1, Rrp9, Grwd1, Pik3r1, Hnrnpc, and Prpf40a) were identified. In addition, eleven TFs (Chd2, Zmiz1, Myb, Etv4, Rela, Tcf4, Tcf12, Chd1, Mef2a, Ubtf, and Mxi1) were predicted to regulate more than two of these hub genes. The expression levels of ten randomly selected hub genes that were specifically differentially expressed in the MDD-like animal model were verified in the corresponding regions in the human brain. These hub genes and TFs may be regarded as potential targets for future MDD treatment strategies, thus aiding in the development of new therapeutic approaches to MDD.

show abstract

Section: Discussionmentioning

confidence: 99%

Analysis of Differentially Expressed Genes in the Dentate Gyrus and Anterior Cingulate Cortex in a Mouse Model of Depression

Wei

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…However, it is relevant to note that the molecular mechanisms seem to differ between brain regions. Indeed, in hippocampus, DHPG-LTD is considered to be independent of PLC/IP 3 pathway and postsynaptic Ca 2+ (Schnabel et al, 1999 ; Fitzjohn et al, 2001 ; Mockett et al, 2011 ; Kim et al, 2015 ), but there is also evidence of IP 3 mediated ER-Ca 2+ release from dendritic spines and calmodulin activation for group I mGluR LTD (Holbro et al, 2009 ; Sethna et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Store-Operated Calcium Entry Is Required for mGluR-Dependent Long Term Depression in Cortical Neurons

González-Sánchez

Arco

Esteban

et al. 2017

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Store-operated calcium entry (SOCE) is a Calcium (Ca2+) influx pathway activated by depletion of intracellular stores that occurs in eukaryotic cells. In neurons, the presence and functions of SOCE are still in question. Here, we show evidences for the existence of SOCE in primary mouse cortical neurons. Endoplasmic reticulum (ER)-Ca2+ depletion using thapsigargin (Tg) triggered a maintained cytosolic Ca2+ increase, which rapidly returned to basal level in the presence of the SOCE blockers 2-Aminoethoxydiphenyl borate (2-APB) and YM-58483. Neural SOCE is also engaged by activation of metabotropic glutamate receptors (mGluRs) with (S)-3,5-dihydroxyphenylglycine (DHPG) (agonist of group I mGluRs), being an essential mechanism to maintain the mGluR-driven Ca2+ signal. Activation of group I of mGluRs triggers long-term depression (LTD) in many brain regions, but the underlying mechanism and, specifically, the necessity of Ca2+ increase in the postsynaptic neuron is controversial. In primary cortical neurons, we now show that the inhibition of Ca2+ influx through SOCE impaired DHPG-LTD, pointing out a key function of calcium and SOCE in synaptic plasticity.

show abstract

“…In particular, canonical mGlu5 receptor signaling might be influenced by ligand bias, location bias and cell type bias, as well as by age-related alterations and differences in receptor isoforms and formation of multimeric complexes with other GPCRs [44]. Also, there is evidence that mGlu1/5 receptors may trigger both PLC-dependent and independent changes in intracellular calcium which in turn may regulate mGlu-LTD through calmodulin and calmodulin-dependent kinases [45].…”

Section: Discussionmentioning

confidence: 99%

Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus

Mango

Braksator

Battaglia

et al. 2017

Pharmacological Research

View full text Add to dashboard Cite

a b s t r a c tAcid-sensing ion channels (ASICs), members of the degenerin/epithelial Na + channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca 2+ and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor-dependent long-term depression (LTD) in the hippocampus. We found that ASIC1a channels mediate a component of LTD in P30-40 animals, since the ASIC1a selective blocker psalmotoxin-1 (PcTx1) reduced the magnitude of LTD induced by application of the group I mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) or induced by paired-pulse low frequency stimulation (PP-LFS). Conversely, PcTx1 did not affect LTD in P13-18 animals. We also provide evidence that ASIC1a is involved in group I mGlu receptor-induced increase in action potential firing. However, blockade of ASIC1a did not affect DHPG-induced polyphosphoinositide hydrolysis, suggesting the involvement of some other molecular partners in the functional crosstalk between ASIC1a and group I mGlu receptors. Notably, PcTx1 was able to prevent the increase in GluA1 S845 phosphorylation at the post-synaptic membrane induced by group I mGlu receptor activation. These findings suggest a novel function of ASIC1a channels in the regulation of group I mGlu receptor synaptic plasticity and intrinsic excitability.

show abstract

Calmodulin activity regulates group I metabotropic glutamate receptor‐mediated signal transduction and synaptic depression

Cited by 10 publications

References 40 publications

Analysis of Differentially Expressed Genes in the Dentate Gyrus and Anterior Cingulate Cortex in a Mouse Model of Depression

Analysis of Differentially Expressed Genes in the Dentate Gyrus and Anterior Cingulate Cortex in a Mouse Model of Depression

Store-Operated Calcium Entry Is Required for mGluR-Dependent Long Term Depression in Cortical Neurons

Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus

Contact Info

Product

Resources

About