Locus coeruleus neuromelanin accumulation and dissipation across the lifespan DOI Creative Commons
Elizabeth Riley, Nicholas G. Cicero, Khena M. Swallow

et al.

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

Published: Oct. 19, 2023

Abstract The pigment neuromelanin, produced in the locus coeruleus (LC) as a byproduct of catecholamine synthesis, gives “blue spot” its name, and both identifies LC neurons is thought to play an important yet complex role normal pathological aging. Using neuromelanin-sensitive T1-weighted turbo spin echo MRI scans we characterized volume neuromelanin signal intensity 96 participants between ages 19 86. Although did not change significantly throughout lifespan, increased from early adulthood, peaked around age 60 precipitously declined thereafter. Neuromelanin was greater caudal relative rostral extent women men. With regard function, associated with fluid cognition older adults (60+) only those above 50th percentile cognitive ability for age. gradual accumulation across sudden dissipation later life, relation preserved consistent

Language: Английский

Anything but small: Microarousals stand at the crossroad between noradrenaline signaling and key sleep functions DOI Creative Commons
Anita Lüthi, Maiken Nedergaard

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Continuous sleep restores the brain and body, whereas fragmented harms cognition health. Microarousals (MAs), brief (3- to 15-s-long) wake intrusions into sleep, are clinical markers for various disorders. Recent rodent studies show that MAs during healthy non-rapid eye movement (NREM) driven by infraslow fluctuations of noradrenaline (NA) in coordination with electrophysiological rhythms, vasomotor activity, cerebral blood volume, glymphatic flow. hence part dynamics, raising questions about their biological roles. We propose bolster NREM sleep's benefits associated NA fluctuations, according an inverted U-shaped curve. Weakened noradrenergic as may occur neurodegenerative diseases or aids, reduce MAs, exacerbated caused stress fragment collapse signaling. suggest crucial restorative plasticity-promoting functions advance our insight normal pathological arousal dynamics from sleep.

Language: Английский

Citations

4
Exploring the Comprehensive Neuroprotective and Anticancer Potential of Afzelin DOI Creative Commons
Mateusz Kciuk, Nitika Garg, Sanchit Dhankhar

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 701 - 701

Published: May 28, 2024

Neurodegenerative diseases (Alzheimer’s disease, Parkinson’s Huntington’s and others) cancer, seemingly disparate in their etiology manifestation, exhibit intriguing associations certain cellular molecular processes. Both cancer neurodegenerative involve the deregulation of processes such as apoptosis, proliferation, DNA repair pose a significant global health challenge. Afzelin (kaempferol 3-O-rhamnoside) is flavonoid compound abundant various plant sources. exhibits diverse range biological activities, offering promising prospects for treatment hallmarked by oxidative stress cell death pathways. Its protective potential against also alleviating side effects chemotherapy. This review explores therapeutic implications afzelin, including its capacity to mitigate stress, modulate inflammation, promote regeneration diseases.

Language: Английский

Citations

6
Riddles in the dark: Decoding the relationship between neuromelanin and neurodegeneration in locus coeruleus neurons DOI Creative Commons

Alexa F. Iannitelli,

David Weinshenker

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 152, P. 105287 - 105287

Published: June 15, 2023

Language: Английский

Citations

14
Regenerating Locus Coeruleus‐Norepinephrine (LC‐NE) Function: A Novel Approach for Neurodegenerative Diseases DOI Creative Commons

Ya-Na Yang,

Yunlong Tao

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

ABSTRACT Pathological changes in the locus coeruleus‐norepinephrine (LC‐NE) neurons, major source of norepinephrine (NE, also known as noradrenaline) brain, are evident during early stages neurodegenerative diseases (ND). Research on both human and animal models have highlighted therapeutic potential targeting LC‐NE system to mitigate progression ND alleviate associated psychiatric symptoms. However, widespread degeneration presents a significant challenge for direct intervention ND. Recent advances regenerative cell therapy offer promising new strategies treatment. The regeneration from pluripotent stem cells (PSCs) could significantly broaden scope LC‐NE‐based therapies In this review, we delve into fundamental background physiological functions LC‐NE. Additionally, systematically examine evidence role neuropathology over recent years. Notably, focus significance PSCs‐derived its impact therapy. A deeper understanding further investigation function pave way practical effective treatments

Language: Английский

Citations

0
Age-related differences in locus coeruleus intensity across a demographically diverse sample DOI
Elizabeth Riley,

Nicholas Cicero,

Senegal Alfred Mabry

et al.

Neurobiology of Aging, Journal Year: 2025, Volume and Issue: 150, P. 122 - 131

Published: March 13, 2025

Language: Английский

Citations

0
Tyrosinase-induced neuromelanin accumulation triggers rapid dysregulation and degeneration of the mouse locus coeruleus DOI Creative Commons

Alexa F. Iannitelli,

Leslie Hassenein,

Bernard Mulvey

et al.

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

Published: March 10, 2023

Abstract The locus coeruleus (LC), the major source of norepinephrine (NE) in brain, is an early site pathology both Alzheimer’s disease (AD) and Parkinson’s (PD), it undergoes catastrophic degeneration later disorders. Dysregulation LC thought to contribute prodromal symptoms AD PD such as anxiety sleep disturbances, while frank LC-NE loss promotes cognitive decline. However, mechanisms responsible for its selective vulnerability are unknown. among only structures brain that produces appreciable amounts neuromelanin (NM), a dark cytoplasmic pigment. It has been proposed NM initially plays protective role by sequestering toxic catecholamine metabolites heavy metals, but may become harmful during aging overwhelms cellular machinery released neurodegeneration. Rodents do not naturally produce NM, limiting study causal relationships between pathology. Adapting viral-mediated approach expression human tyrosinase, enzyme peripheral melanin production, we successfully promoted pigmentation mouse neurons recapitulates key ultrastructural features endogenous found primates. Pigment results neuron hyperactivity, reduced tissue NE levels, transcriptional changes, novelty-induced phenotypes 1-week post-injection. By 6-10 weeks, accumulation associated with severe neurodegeneration microglial engulfment pigment granules, anxiety-like behavior abated. These reminiscent dysfunction cell death PD, validating this model studying consequences relates neurodegenerative disease.

Language: Английский

Citations

8
Neuromodulatory systems in aging and disease DOI
Martin J. Dahl, Markus Werkle‐Bergner, Mara Mather

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 162, P. 105647 - 105647

Published: April 2, 2024

Language: Английский

Citations

0
Locus coeruleus neuromelanin accumulation and dissipation across the lifespan DOI Creative Commons
Elizabeth Riley, Nicholas G. Cicero, Khena M. Swallow

et al.

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

Published: Oct. 19, 2023

Abstract The pigment neuromelanin, produced in the locus coeruleus (LC) as a byproduct of catecholamine synthesis, gives “blue spot” its name, and both identifies LC neurons is thought to play an important yet complex role normal pathological aging. Using neuromelanin-sensitive T1-weighted turbo spin echo MRI scans we characterized volume neuromelanin signal intensity 96 participants between ages 19 86. Although did not change significantly throughout lifespan, increased from early adulthood, peaked around age 60 precipitously declined thereafter. Neuromelanin was greater caudal relative rostral extent women men. With regard function, associated with fluid cognition older adults (60+) only those above 50th percentile cognitive ability for age. gradual accumulation across sudden dissipation later life, relation preserved consistent

Language: Английский

Citations

0