Coupling of mitochondrial state with active zone plasticity in early brain aging DOI Creative Commons
Fei Lu, YongTian Liang, Ulrich Kintscher

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 79, P. 103454 - 103454

Published: Dec. 3, 2024

Neurodegenerative diseases typically emerge after an extended prodromal period, underscoring the critical importance of initiating interventions during early stages brain aging to enhance later resilience. Changes in presynaptic active zone proteins ("PreScale") are considered a dynamic, resilience-enhancing form plasticity process early, still reversible Drosophila brain. Aging, however, triggers significant changes not only synapses but also mitochondria. While two organelles spaced close proximity, likely reflecting direct functional coupling regard ATP and Ca

Language: Английский

Alcohol induces long-lasting sleep deficits in Drosophila via subsets of cholinergic neurons DOI

Maggie M. Chvilicek,

Iris Titos, Collin B. Merrill

et al.

Current Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

3
Sleep deprivation drives brain-wide changes in cholinergic presynapse abundance in Drosophila melanogaster DOI Creative Commons
Jacqueline T. Weiss, Mei Z. Blundell,

Prabhjit Singh

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(13)

Published: March 18, 2024

Sleep is an evolutionarily conserved state that supports brain functions, including synaptic plasticity, in species across the animal kingdom. Here, we examine neuroanatomical and cell-type distribution of presynaptic scaling fly after sleep loss. We previously found loss drives accumulation active zone scaffolding protein Bruchpilot (BRP) within cholinergic Kenyon cells Drosophila melanogaster mushroom body (MB), but not other classes MB neurons. To test whether similar cell type–specific trends plasticity occur broadly brain, used a flp-based genetic reporter to label BRP cholinergic, dopaminergic, GABAergic, or glutamatergic then collected whole-brain confocal image stacks intensity systematically quantify BRP, marker presynapse abundance, 37 neuropil regions central brain. Our results indicate loss, either by overnight (12-h) mechanical stimulation chronic disruption insomniac mutants, elevates synapse abundance while neurons produce neurotransmitters undergoes weaker, if any, changes. Extending deprivation 24 h brain-wide upscaling glutamatergic, other, synapses. Finally, male–male social pairings induce increased excitatory synapses despite male–female eliciting more waking activity, suggesting experience-specific plasticity. Within neurotransmitter class context, changes are domains, indicating rules may apply during acute need alter excitatory–inhibitory balance

Language: Английский

Citations

9
Divergent evolution of sleep in Drosophila species DOI Creative Commons

Michaela Joyce,

Federica A. Falconio, Laurence Blackhurst

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 14, 2024

Abstract Living organisms synchronize their biological activities with the earth’s rotation through circadian clock, a molecular mechanism that regulates biology and behavior daily. This synchronization factually maximizes positive (e.g., social interactions, feeding) during safe periods, minimizes exposure to dangers predation, darkness) typically at night. Beyond basic regulation, some behaviors like sleep have an additional layer of homeostatic control, ensuring those essential are fulfilled. While is predominantly governed by secondary regulator, though not well-understood, ensures adherence necessary amounts hints fundamental function beyond simple energy conservation safety. Here we explore regulation across seven Drosophila species diverse ecological niches, revealing while circadian-driven aspects consistent, varies significantly. The findings suggest in Drosophilids, evolved primarily for purposes. more complex, homeostatically regulated functions appear independently species-specific manner, universally conserved. laboratory model may reproduce recapitulate primordial evolution.

Language: Английский

Citations

8
Developing forebrain synapses are uniquely vulnerable to sleep loss DOI Creative Commons
Sean M. Gay, Elissavet Chartampila,

Julia S. Lord

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(44)

Published: Oct. 23, 2024

Sleep is an essential behavior that supports lifelong brain health and cognition. Neuronal synapses are a major target for restorative sleep function locus of dysfunction in response to deprivation (SD). Synapse density highly dynamic during development, becoming stabilized with maturation adulthood, suggesting exerts distinct synaptic functions between development adulthood. Importantly, problems common neurodevelopmental disorders including autism spectrum disorder (ASD). Moreover, early life disruption animal models causes long-lasting changes adult behavior. Divergent plasticity engaged necessarily implies developing will show differential vulnerability SD. To investigate mechanisms SD across we systematically examined the behavioral molecular responses acute juvenile (P21 P28), adolescent (P42 P49), (P70 P100) mice both sexes. Compared adults, juveniles lack robust adaptations SD, precipitating cognitive deficits novel object recognition task. Subcellular fractionation, combined proteome phosphoproteome analysis revealed synapse profoundly vulnerable whereas adults exhibit comparative resilience. juveniles, not older mice, aberrantly drives induction potentiation, synaptogenesis, expression perineuronal nets. Our further reveals as putative node convergence ASD genetic risk. Together, our systematic developmental how impacts key aspects providing insights susceptibility.

Language: Английский

Citations

6
ninna nanna links circadian and homeostatic sleep drive in Drosophila DOI Creative Commons
Anne Petzold, Giorgio F. Gilestro

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

Published: May 14, 2024

Sleep is under control of two processes – circadian and homeo-static regulation but little known about how these integrate. Here, we identify a Drosophila gene, ninna nanna , encoding alternatively spliced isoforms: Ninna Nanna. Both proteins encode aldo-keto reductases are expressed in different, yet interconnected neurons. One isoform, encodes an reductase with predicted affinity for NADP(H) key pacemaker neurons, the s-LN v s. The second NAD(H) ICLI pair wake-promoting peptidergic neurons whose inhibition relieves sleep pressure. interconnect to integrate binary sensing circuit which receives information homeostatic defines archetypal integration drive reinforces hypothesized link between regulation.

Language: Английский

Citations

1
Socialization causes long-lasting behavioral changes DOI Creative Commons
Beatriz Gil-Martí,

Julia Isidro-Mézcua,

Adriana Poza-Rodriguez

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 27, 2024

Abstract In modern human societies, social isolation acts as a negative factor for health and life quality. On the other hand, interaction also has profound effects on animal human, impacting aggressiveness, feeding sleep, among many behaviors. Here, we observe that in fly Drosophila melanogaster these behavioral changes long-last even after ceased, suggesting socialization experience triggers plasticity. These modified behaviors maintain similar levels 24 h persist up to 72 h, although showing progressive decay. We find impairing long-term memory mechanisms either genetically or by anesthesia abolishes expected response interaction. Furthermore, show increases CREB-dependent neuronal activity synaptic plasticity mushroom body, main insect center analogous mammalian hippocampus. propose awareness, understood long-lasting behavior caused with mechanistic similarities formation.

Language: Английский

Citations

1
Developing forebrain synapses are uniquely vulnerable to sleep loss DOI Open Access
Sean M. Gay, Elissavet Chartampila,

Julia S. Lord

et al.

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

Published: Nov. 7, 2023

Abstract Sleep is an essential behavior that supports lifelong brain health and cognition. Neuronal synapses are a major target for restorative sleep function locus of dysfunction in response to deprivation (SD). Synapse density highly dynamic during development, becoming stabilized with maturation adulthood, suggesting exerts distinct synaptic functions between development adulthood. Importantly, problems common neurodevelopmental disorders including autism spectrum disorder (ASD). Moreover, early life disruption animal models causes long lasting changes adult behavior. Different plasticity engaged necessarily implies developing will show differential vulnerability SD. To investigate mechanisms SD across we systematically examined the behavioral molecular responses acute juvenile (P21-28), adolescent (P42-49) (P70-100) mice both sexes. Compared adults, juveniles lack robust adaptations SD, precipitating cognitive deficits novel object recognition test. Subcellular fractionation, combined proteome phosphoproteome analysis revealed synapse profoundly vulnerable whereas adults exhibit comparative resilience. juveniles, not older mice, aberrantly drives induction potentiation, synaptogenesis, expression peri-neuronal nets. Our further reveals as convergent node ASD genetic risk. Together, our systematic developmental how impacts key aspects providing mechanistic insights susceptibility. Significance Statement fundamental pillar health. commonly associated conditions (ASD) schizophrenia. Therefore, understanding vulnerabilities loss research question. Here systemically examine consequence (SD) mice. absent or blunted adaptive heightened sensitivity SD-induced deficits. indicates plays important role effects converge on nodes risk ASD. This study provides new into healthy development.

Language: Английский

Citations

2
Socialization causes long-lasting behavioral changes DOI Creative Commons
Beatriz Gil-Martí,

Julia Isidro-Mézcua,

Adriana Poza-Rodriguez

et al.

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

Published: April 28, 2024

SUMMARY In modern human societies, social isolation acts as a negative factor for health and life quality. On the other hand, interaction also has profound effects on animal behaviors, reducing aggressiveness, feeding loss of sleep. Here, we observe that in fly Drosophila melanogaster these behavioral changes long-last even after ceased, suggesting socialization experience triggers plasticity. We find impairing long-term memory mechanisms either genetically or by anesthesia abolishes expected response to interaction. Furthermore, show increases CREB-dependent neuronal activity synaptic plasticity mushroom body, main insect center analogous mammalian hippocampus. propose awareness, understood long-lasting behavior caused with mechanistic similarities formation.

Language: Английский

Citations

0
Coupling of mitochondrial state with active zone plasticity in early brain aging DOI Creative Commons
Fei Lu, YongTian Liang, Ulrich Kintscher

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 79, P. 103454 - 103454

Published: Dec. 3, 2024

Neurodegenerative diseases typically emerge after an extended prodromal period, underscoring the critical importance of initiating interventions during early stages brain aging to enhance later resilience. Changes in presynaptic active zone proteins ("PreScale") are considered a dynamic, resilience-enhancing form plasticity process early, still reversible Drosophila brain. Aging, however, triggers significant changes not only synapses but also mitochondria. While two organelles spaced close proximity, likely reflecting direct functional coupling regard ATP and Ca

Language: Английский

Citations

0