The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders DOI Creative Commons
Alessandro Galgani,

Marco Scotto,

Filippo Sean Giorgi

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(9), P. 10180 - 10199

Published: Sept. 14, 2024

Neuromodulatory subcortical systems (NSSs) are monoaminergic and cholinergic neuronal groups that markedly precociously involved in the pathogenesis of many neurodegenerative disorders (NDDs), including Parkinson’s Alzheimer’s diseases. In humans, although tools have been developed to infer information on these nuclei, encompassing neuroimaging neurophysiological methods, a detailed specific direct evaluation their cellular features vivo has difficult obtain until recent years. The development induced pluripotent stem cell (iPSC) models allowed research deeply delve into molecular biology NSS neurons. fact, iPSCs can be produced easily non-invasively from patients’ fibroblasts or circulating blood monocytes, by de-differentiating those cells using protocols, then re-differentiated towards neural phenotypes, which may reproduce correspondent brain neurons (including ones) same patient. this review, we summarized findings obtained field NDDs iPSCs, with aim understand how reliably might represent vitro NSS. We found most current literature NSSs focused midbrain dopaminergic disease, providing interesting results pathophysiology even leading first human autologous transplantation. Differentiation protocols for noradrenergic, cholinergic, serotoninergic also recently defined published. Thus, it expected near future, approach could extend other NDDs.

Language: Английский

Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease DOI Creative Commons
Chen‐Pei Lin, Irene Frigerio,

John G. J. M. Bol

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Feb. 9, 2024

Abstract Background Degeneration of the locus coeruleus (LC) noradrenergic system contributes to clinical symptoms in Alzheimer’s disease (AD) and Parkinson’s (PD). Diffusion magnetic resonance imaging (MRI) has potential evaluate integrity LC system. The aim current study was determine whether diffusion MRI-measured its tracts are sensitive degeneration AD PD. Methods Post-mortem situ T1-weighted multi-shell MRI performed for 9 AD, 14 PD, 8 control brain donors. Fractional anisotropy (FA) mean diffusivity were derived from LC, between anterior cingulate cortex, dorsolateral prefrontal cortex (DLPFC), primary motor (M1) or hippocampus. Brain tissue sections cortical regions obtained immunostained dopamine-beta hydroxylase (DBH) quantify cell density fiber load. Group comparisons correlations outcome measures using linear regression partial correlations. Results PD cases showed loss cells fibers. In increased DBH + immunoreactivity DLPFC compared controls, while reduced M1 controls. Higher FA within found which correlated with fibers LC. Increased LC-DLPFC tract combined group, whereas LC-M1 neuronal group. alterations not immunoreactivity. Conclusions MRI-detected associated local rather than changes cortex.

Language: Английский

Citations

11
Application of Neuromelanin MR Imaging in Parkinson Disease DOI Creative Commons
Naying He, Yongsheng Chen, Peter A. LeWitt

et al.

Journal of Magnetic Resonance Imaging, Journal Year: 2022, Volume and Issue: 57(2), P. 337 - 352

Published: Aug. 26, 2022

MRI has been used to develop biomarkers for movement disorders such as Parkinson disease (PD) and other neurodegenerative with parkinsonism progressive supranuclear palsy multiple system atrophy. One of these imaging is neuromelanin (NM), whose integrity can be assessed from its contrast volume. NM found mainly in certain brain stem structures, namely, the substantia nigra pars compacta (SNpc), ventral tegmental area, locus coeruleus. Another major biomarker iron, which often increases concert degeneration. These have potential improve diagnostic certainty differentiating between PD similar PD, well provide a better understanding pathophysiology. Mapping vivo clinical importance gauging premotor phase when there greater than 50% loss dopaminergic SNpc melanized neurons. As metal ion chelator, absorb iron. When released neurons, it deposits iron into intracellular tissues SNpc; result that imaged measured using quantitative susceptibility mapping. An increase also leads disappearance nigrosome‐1 sign, another neuroimage PD. Therefore, mapping changes are practical means improving early diagnosis monitoring progression. In this review, we discuss functions location NM, how NM‐MRI performed, automatic content, NM‐related enhance differentiate disorders, advances methods. With currently evolving rapid artificial intelligence, likely increasingly important roles enhancing capabilities Evidence Level 1 Technical Efficacy Stage 2

Language: Английский

Citations

27
Magnetic resonance imaging Locus Coeruleus abnormality in amnestic Mild Cognitive Impairment is associated with future progression to dementia DOI Creative Commons
Alessandro Galgani, Francesco Lombardo, Nicola Martini

et al.

European Journal of Neurology, Journal Year: 2022, Volume and Issue: 30(1), P. 32 - 46

Published: Sept. 10, 2022

Human neuropathological studies indicate that the pontine nucleus Locus Coeruleus (LC) undergoes significant and early degeneration in Alzheimer's disease. This line of evidence alongside experimental data suggests LC functional/structural decay may represent a critical factor for disease pathophysiological clinical progression. In present prospective study, we used Magnetic Resonance Imaging (MRI) with LC-sensitive sequence (LC-MRI) to investigate vivo involvement progression, whether specific LC-MRI features at baseline are associated prognosis cognitive performance amnestic Mild Cognitive Impairment.LC-MRI parameters were measured by template-based method on 3.0-T magnetic resonance images 34 patients dementia, 73 Impairment, 53 cognitively intact individuals. A thorough neurological neuropsychological assessment was performed 2.5-year follow-up.In subjects Impairment who converted dementia (n = 32), intensity number LC-related voxels significantly lower than individuals, resembling those observed demented patients. Such reduction not detected remained stable follow-up. converting parameter maximal rostral part left nucleus. Structural equation modeling analysis showed positively correlate performance.Our findings highlight potential role predicting progression support key Alzheimer continuum.

Language: Английский

Citations

24
Imaging Biomarkers in Prodromal and Earliest Phases of Parkinson’s Disease DOI Creative Commons
Hendrik Theis, Nicola Pavese, Irena Rektorová

et al.

Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: 14(s2), P. S353 - S365

Published: Feb. 6, 2024

Assessing imaging biomarker in the prodromal and early phases of Parkinson’s disease (PD) is great importance to ensure an safe diagnosis. In last decades, modalities advanced are now able assess many different aspects neurodegeneration PD. MRI sequences can measure iron content or neuromelanin. Apart from SPECT with Ioflupane, more specific PET tracers degeneration dopaminergic system available. Furthermore, metabolic patterns be used anticipate a phenoconversion PD manifest this regard, it worth mentioning that inflammation will gain significance. Molecular neurotransmitters like serotonin, noradrenaline acetylcholine shed light on non-motor symptoms. Outside brain, molecular heart gut PD-related autonomous nervous system. Moreover, optical coherence tomography noninvasively detect retinal fibers as potential review, we describe these state-of-the-art point out how far techniques future pave way towards biomarker-based staging

Language: Английский

Citations

6
Locus coeruleus features are linked to vagus nerve stimulation response in drug-resistant epilepsy DOI Creative Commons
Alexandre Berger, Elise Beckers, Vincent Joris

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 13, 2024

The locus coeruleus–norepinephrine system is thought to be involved in the clinical effects of vagus nerve stimulation. This known prevent seizure development and induce long-term plastic changes, particularly with release norepinephrine hippocampus. However, requisites become responder therapy mechanisms action are still under investigation. Using MRI, we assessed structural functional characteristics coeruleus microstructural properties coeruleus-hippocampus white matter tracts patients drug-resistant epilepsy responding or not therapy. Twenty-three epileptic cervical stimulation were recruited for this pilot study, including 13 responders partial 10 non-responders. A dedicated MRI acquisition allowed vivo localization computation its contrast (an accepted marker LC integrity). Locus activity was estimated using during an auditory oddball task. Finally, multi-shell diffusion used estimate tracts. These compared between responders/partial non-responders their association duration also explored. In a better response therapy, trends toward lower higher found left medial right caudal portions coeruleus, respectively. An increased contrast, bilaterally over portions, correlated treatment. integrity connections new insights into neurobiology may provide novel markers treatment reflect neuroplasticity occurring brain following implantation.

Language: Английский

Citations

6
Noradrenergic neuromodulation in ageing and disease DOI Creative Commons

Friedrich Krohn,

Elisa Lancini, Mareike Ludwig

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 152, P. 105311 - 105311

Published: July 10, 2023

The locus coeruleus (LC) is a small brainstem structure located in the lower pons and main source of noradrenaline (NA) brain. Via its phasic tonic firing, it modulates cognition autonomic functions involved brain's immune response. extent degeneration to LC healthy ageing remains unclear, however, noradrenergic dysfunction may contribute pathogenesis Alzheimer's (AD) Parkinson's disease (PD). Despite their differences progression at later stages, early involvement lead comparable behavioural symptoms such as preclinical sleep problems neuropsychiatric result AD PD pathology. In this review, we draw attention mechanisms that underlie ageing, PD. We aim motivate future research investigate how system play pivotal role which also be relevant other neurodegenerative diseases.

Language: Английский

Citations

13
Locus coeruleus integrity and neuropsychiatric symptoms in a cohort of early‐ and late‐onset Alzheimer's disease DOI Creative Commons
Neus Falgàs,

Marta Peña‐González,

Andrea Val‐Guardiola

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6351 - 6364

Published: July 25, 2024

Early-onset Alzheimer's disease (EOAD) shows a higher burden of neuropsychiatric symptoms than late-onset (LOAD). We aim to determine the differences in severity and locus coeruleus (LC) integrity between EOAD LOAD accounting for stage.

Language: Английский

Citations

5
Exploring the Role of Locus Coeruleus in Alzheimer’s Disease: a Comprehensive Update on MRI Studies and Implications DOI Creative Commons
Alessandro Galgani, Filippo Sean Giorgi

Current Neurology and Neuroscience Reports, Journal Year: 2023, Volume and Issue: 23(12), P. 925 - 936

Published: Dec. 1, 2023

Abstract Purpose of Review Performing a thorough review magnetic resonance imaging (MRI) studies assessing locus coeruleus (LC) integrity in ageing and Alzheimer’s disease (AD), contextualizing them with current preclinical neuropathological literature. Recent Findings MRI successfully detected LC alterations AD, identifying degenerative phenomena involving this nucleus even the prodromal stages disorder. The degree disruption was also associated severity AD cortical pathology, cognitive behavioral impairment, risk clinical progression. Summary Locus coeruleus-MRI has proved to be useful tool assess central noradrenergic system vivo humans. It allowed test patients experimental hypothesis, thus confirming specific marked involvement its key pathogenetic role. coeruleus-MRI–related data might represent theoretical basis on which start developing drugs target AD.

Language: Английский

Citations

11
Lithium engages autophagy for neuroprotection and neuroplasticity: Translational evidence for therapy DOI
Stefano Puglisi‐Allegra, Gloria Lazzeri, Carla L. Busceti

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 148, P. 105148 - 105148

Published: March 28, 2023

Language: Английский

Citations

10
Locus Coeruleus-Norepinephrine System: Spheres of Influence and Contribution to the Development of Neurodegenerative Diseases DOI Creative Commons
Vladimir N. Nikolenko, Irina Dmitriyevna Borminskaya, Arina T. Nikitina

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(3)

Published: March 20, 2024

Locus coeruleus is a small bilateral nucleus in the brainstem. It main source of norepinephrine (noradrenaline) throughout central nervous system (about 70% all system), and, as shown numerous studies, it involved regulating significant number functions. The detailed study functions Coeruleus (LC) and its significance human life became possible only after development histofluorescence methods for monoamines 1960s. widespread locus coeruleus-norepinephrine (LC-NE) projection regulates entire modulates sensory processing, motor behavior, arousal, cognitive processes. Damage to LC associated decrease levels are wide range clinical conditions pathological Although much about anatomy physiology currently known, ultimate role regulation control sleep-wake cycle, stress response, (such Alzheimer’s disease, dementia, depression, suicidal chronic traumatic encephalopathy, Parkinson’s disease) not fully understood. Non-invasive visualization can be used differential diagnosis, determining stage predicting course. Studying dysfunction LC-norepinephrine system, pathogenesis various neurological diseases, may ultimately form basis new treatment based on pharmacological elevation levels. In this review, we will attempt highlight key points regarding structure function Coeruleus, well outline directions prospects study.

Language: Английский

Citations

4