A Novel Role for Phospholamban in the Thalamic Reticular Nucleus DOI Open Access

Benjamin Klocke,

Aikaterini Britzolaki, Joseph Saurine

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 23, 2023

ABSTRACT The thalamic reticular nucleus (TRN) is a critical brain region that greatly influences vital neurobehavioral processes, including executive functioning and the generation of sleep rhythms. Recently, TRN dysfunction was suggested to underlie hyperactivity, attention deficits, disturbances observed across various devastating neurodevelopmental disorders, autism, schizophrenia attention-deficit/hyperactivity disorder (ADHD). Notably, highly specialized sarco- endoplasmic reticulum calcium (Ca 2+ ) ATPase 2 (SERCA2)-dependent Ca signaling network operates in dendrites neurons regulate their high-frequency bursting activity. Phospholamban (PLN) prominent regulator SERCA2 with an established role maintaining homeostasis heart; although interaction PLN has been largely regarded as cardiac-specific, our findings challenge this view suggest extends beyond cardiovascular system impact function. Specifically, we found be expressed adult mouse utilized global constitutive innovative conditional genetic models, combination 5-choice serial reaction time task (5-CSRTT) electroencephalography (EEG)-based somnography assess regulating sleep, two complex behaviors map onto circuits. Overall, results present study show perturbed function aberrant behavioral phenotypes mice (i.e., impulsivity deficits) support novel for neurocircuitry.

Language: Английский

Impact of Metal Ions on Cellular Functions: A Focus on Mesenchymal Stem/Stromal Cell Differentiation DOI Open Access
Kirsten Peters,

Susanne Staehlke,

Henrike Rebl

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 10127 - 10127

Published: Sept. 20, 2024

Metals play a crucial role in the human body, especially as ions metalloproteins. Essential metals, such calcium, iron, and zinc are for various physiological functions, but their interactions within biological networks complex not fully understood. Mesenchymal stem/stromal cells (MSCs) essential tissue regeneration due to ability differentiate into cell types. This review article addresses effects of unphysiological, directly toxic, metal ion concentrations, particularly concerning MSCs. Overloading or unbalancing concentrations can significantly impair function differentiation capacity In addition, excessive unbalanced lead oxidative stress, which affect viability inflammation. Data on MSC limited often contradictory. Future research should, therefore, aim clarify mechanisms by differentiation, focusing aspects interactions, exposure duration, other environmental conditions. Understanding these could ultimately improve design biomaterials implants promote MSC-mediated regeneration. It also development innovative therapeutic strategies regenerative medicine.

Language: Английский

Citations

11
High-Throughput Identification of Calcium Regulated Proteins Across Diverse Proteomes DOI Creative Commons
Timothy M. Locke, Rose Fields,

Hayden Gizinski

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 18, 2024

Calcium ions play important roles in nearly every biological process, yet whole-proteome analysis of calcium effectors has been hindered by lack high-throughput, unbiased, and quantitative methods to identify proteins-calcium engagement. To address this, we adapted protein thermostability assays the budding yeast, human cells, mouse mitochondria. Based on calcium-dependent thermostability, identified 2884 putative calcium-regulated proteins across human, mouse, yeast proteomes. These data revealed engagement novel signaling hubs cellular processes, including metabolic enzymes spliceosome. Cross-species comparison calcium-protein mutagenesis experiments residue-specific cation engagement, even within well-known EF-hand domains. Additionally, found that dienoyl-CoA reductase DECR1 binds at physiologically-relevant concentrations with substrate-specific affinity, suggesting direct regulation mitochondrial fatty acid oxidation. proteomic analyses establish a key resource dissect its mechanistic effects multiple species diverse processes.

Language: Английский

Citations

4
Role of calcium overload-mediated disruption of mitochondrial dynamics in offspring neurotoxicity due to methylmercury exposure during pregnancy and lactation DOI Creative Commons

Lingxu Kong,

Huajie Yang, Jing Yang

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 291, P. 117835 - 117835

Published: Feb. 1, 2025

Language: Английский

Citations

0
Defined culture conditions robustly maintain human stem cell pluripotency, highlighting a role for Ca2+ signaling DOI Creative Commons
Ilse Eidhof, Benjamin Ulfenborg,

Malin Kele

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 18, 2025

Abstract Induced pluripotent stem cells (iPSCs) have significant potential for disease modeling and cell therapies. However, their wide-spread application has faced challenges, including batch-to-batch variabilities, notable distinctions when compared to embryonic (ESCs). Some of these disparities can from using undefined culture conditions the reprogramming procedure, however, precise mechanisms remain understudied. Here, we gene expression data over 100 iPSC ESC lines cultivated under defined conditions. Defined significantly reduced inter-PSC line variability, irrespective PSC type, highlighting importance standardization minimize biases. This variability is concurrent with decreased somatic marker germ layer differentiation increased Ca 2+ -binding protein expression. Moreover, SERCA pump inhibition highlighted an important role intracellular activity in maintaining pluripotency Further understanding processes help standardize improve hPSC

Language: Английский

Citations

0
High-throughput identification of calcium-regulated proteins across diverse proteomes DOI Creative Commons
Timothy M. Locke, Rose Fields,

Hayden Gizinski

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(11), P. 114879 - 114879

Published: Oct. 18, 2024

Language: Английский

Citations

3
Integrated analysis of endoplasmic reticulum stress regulators’ expression identifies distinct subtypes of autism spectrum disorder DOI Creative Commons
Yanjun Li,

Songyin Gao,

Yuelan Meng

et al.

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: April 17, 2023

Endoplasmic reticulum (ER) stress has been demonstrated to play important roles in a variety of human diseases. However, their relevance autism spectrum disorder (ASD) remains largely unknown. Herein, we aimed investigate the expression patterns and potential ER regulators ASD. The ASD profiles GSE111176 GSE77103 were compiled from Gene Expression Omnibus (GEO) database. score determined by single sample gene set enrichment analysis (ssGSEA) was significantly higher patients. Differential revealed that there 37 dysregulated Based on profile, random forest artificial neuron network techniques applied build classifier can effectively distinguish control samples among independent datasets. Weighted co-expression (WGCNA) screened out turquoise module with 774 genes closely related score. Through overlapping results differential genes, hub gathered. TF/miRNA-hub interaction networks created. Furthermore, consensus clustering algorithm performed cluster patients, two subclusters. Each subcluster unique profiles, biological functions, immunological characteristics. In 1, FAS pathway more enriched, while 2 had level plasma cell infiltration as well BCR signaling interleukin receptor reaction reactivity. Finally, Connectivity map (CMap) database used find prospective compounds target various A total 136 enriched. addition some specific drugs which reverse each subcluster, found PKC inhibitor BRD-K09991945 targets Glycogen synthase kinase 3β (GSK3B) might have therapeutic effect both subtypes worth experimental validation. Our finding proved plays crucial role diversity complexity ASD, may inform mechanistic assessments disorder.

Language: Английский

Citations

4
Chronic pharmacological activation of SERCA with CDN1163 affects spatial cognitive flexibility but not attention and impulsivity in mice DOI

Benjamin Klocke,

Carter Moore,

Hayden Ott

et al.

Behavioural Pharmacology, Journal Year: 2023, Volume and Issue: 34(8), P. 477 - 487

Published: Oct. 1, 2023

Intracellular calcium (Ca2+) homeostasis is critical for many neural processes, including learning, memory and synaptic plasticity. The sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) among the key regulators that preserve in neurons. SERCAs comprise a set of ubiquitously expressed pumps primarily function to sequester cytosolic into endoplasmic reticular stores. As SERCA has been implicated neurobiology several neuropsychiatric neurodegenerative diseases, pharmacological harnessing its understanding SERCA's role brain physiology pathophysiology. In current study, we employed Morris water maze 5-choice serial reaction time task (5-CSRTT) investigate effects chronic activation SERCA, using small allosteric activator CDN1163, on spatial learning memory, executive functioning naive C57BL/6J mice. Our data show with CDN1163 (20 mg/kg) selectively impairs cognitive flexibility reversal while leaving functions such as attention impulsivity intact. Present findings contribute growing field behavior expand knowledge use an investigational tool study regulating neurobehavioral processes potential therapeutic candidate debilitating disorders.

Language: Английский

Citations

4
Childhood lead exposure increases the risk of attention-deficit-hyperactivity disorder: A meta-analysis DOI

Victoria Rosenauer,

Magdalena Isabell Schwarz,

Thomas Vlasak

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 951, P. 175574 - 175574

Published: Aug. 15, 2024

Language: Английский

Citations

1
Regulation of adult neurogenesis: the crucial role of astrocytic mitochondria DOI Creative Commons
Danping Liu, Pei Guo,

Yi Wang

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Nov. 22, 2024

Neurogenesis has emerged as a promising therapeutic approach for central nervous system disorders. The role of neuronal mitochondria in neurogenesis is well-studied, however, recent evidence underscores the critical astrocytic mitochondrial function regulating and underlying mechanisms remain incompletely understood. This review highlights regulatory effects astrocyte on neurogenesis, focusing metabolic support, calcium homeostasis, secretion neurotrophic factors. effect dysfunction pathophysiology treatment strategies Alzheimer’s disease depression discussed. Greater attention needed to investigate autophagy, dynamics, biogenesis, energy metabolism neurogenesis. Targeting presents potential strategy enhancing neural regeneration.

Language: Английский

Citations

1
Calcium dynamics tune developmental tempo to generate evolutionarily divergent axon tract lengths DOI Creative Commons
Feline W Lindhout,

Hanna M. Szafranska,

Iván Imaz-Rosshandler

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

ABSTRACT The considerably slow pace of human brain development correlates with an evolutionary increase in size, cell numbers, and expansion neuronal structures, axon tracts undergoing even greater than other domains. However, whether tempo is responsible for these differences magnitude, how, remains to be determined. Here, we used organoids investigate this observed that spend more time growing extend farther compared those mice, independent their tissue environment. Single RNA sequencing analysis pointed a subset calcium-permeable ion channels expressed throughout neuron development, including during tract outgrowth. Calcium imaging early consistently revealed reduced calcium influx neurons mouse neurons. Stimulating increasing cAMP levels resulted premature halting outgrowth shorter tracts, mimicking the phenotype, while abrogating led longer phase humans. Thus, regulation set by extending window foster elaborated morphology.

Language: Английский

Citations

1