Noradrenergic modulation of saccades in Parkinson’s disease DOI Creative Commons
Isabella F. Orlando, Frank H. Hezemans, Rong Ye

et al.

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

Published: Jan. 5, 2024

Abstract Noradrenaline is a powerful modulator of cognitive processes, including action-decisions underlying saccadic control. Changes in eye movements are common across neurodegenerative diseases ageing, Parkinson’s disease. With growing interest noradrenergic treatment potential for non-motor symptoms disease, the temporal precision oculomotor function advantageous to assess effects this modulation. Here we studied effect 40 mg atomoxetine, noradrenaline reuptake inhibitor, nineteen people with idiopathic disease using single dose, randomised double-blind crossover placebo-controlled design. Twenty-five healthy adult participants completed assessments provide normative data. Participants performed prosaccade and antisaccade tasks. The latency, velocity accuracy saccades, resting pupil diameter, were measured. Increased diameter on drug confirmed its expected locus coeruleus ascending arousal system. Atomoxetine improved key aspects saccade performance: latencies faster main sequence was normalised. These improvements accompanied by increased error rates drug. Together these findings suggest shift speed-accuracy trade-off visuo-motor decisions response treatment. Our results new evidence substantiate role modulation based known circuitry advance hypothesis that reflects at level coeruleus–superior colliculus pathway. Given related conditions, system can support assessment without limb-motor confounds task performance.

Language: Английский

Declining locus coeruleus–dopaminergic and noradrenergic modulation of long-term memory in aging and Alzheimer’s disease DOI Creative Commons
Martin J. Dahl, Agnieszka Kulesza, Markus Werkle‐Bergner

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 153, P. 105358 - 105358

Published: Aug. 17, 2023

Language: Английский

Citations

22
A systematic review of the neuropathology and memory decline induced by monosodium glutamate in the Alzheimer’s disease-like animal model DOI Creative Commons

Singh S. Ankul,

Lakshmi Chandran,

Anuragh Singh

et al.

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

Published: Oct. 24, 2023

This systematic review analyzes monosodium glutamate (MSG) in the Alzheimer’s disease-like condition to enhance translational research. Our seeks understand how MSG affects brain and causes degenerative disorders. Due significant preclinical data linking toxicity disease lack of a comprehensive or meta-analysis, we initiated study on MSG’s potential link. We searched PubMed, ScienceDirect, ProQuest, DOAJ, Scopus for animal research English language papers without time constraints. used PRISMA-P framework PICO technique collect population, intervention exposure, comparison, result data. It was registered PROSPERO as CRD42022371502. affected mice’s exploratory behaviors short-term working memory. The brain, hippocampus, cerebellar tissue demonstrated neuronal injury-related histological histomorphometric changes. A total 70% MSG-treated mice had poor nesting behavior. treated also more hyperphosphorylated tau protein their cortical hippocampus neurons. Glutamate glutamine levels increased with MSG, dose-dependent mixed horizontal locomotor, grooming, anxiety responses reduced. treatment significantly decreased phospho-CREB levels, supporting idea that neurons were harmed, despite CREB mRNA expression. High doses drastically lower serum serotonin levels. In conclusion, showed AD-like pathology, atrophy, memory impairment. Further longer span deeper behavioral characterization is needed. Systematic registration : https://www.crd.york.ac.uk/prospero/ , identifier [CRD42022371502].

Language: Английский

Citations

14
Causal evidence for cholinergic stabilization of attractor landscape dynamics DOI Creative Commons
Natasha L. Taylor, Christopher J. Whyte, Brandon R. Munn

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(6), P. 114359 - 114359

Published: June 1, 2024

There is substantial evidence that neuromodulatory systems critically influence brain state dynamics; however, most work has been purely descriptive. Here, we quantify, using data combining local inactivation of the basal forebrain with simultaneous measurement resting-state fMRI activity in macaque, causal role long-range cholinergic input to stabilization states cerebral cortex. Local nucleus basalis Meynert (nbM) leads a decrease energy barriers required for an transition cortical ongoing activity. Moreover, particular nbM sub-regions predominantly affects information transfer regions known receive direct anatomical projections. We demonstrate these results simple neurodynamical model impact on neuronal firing rates and slow hyperpolarizing adaptation currents. conclude system plays critical stabilizing macroscale dynamics.

Language: Английский

Citations

5
Monoamine alterations in Alzheimer’s disease and their implications in comorbid neuropsychiatric symptoms DOI Creative Commons
Shalini Saggu,

Ava Bai,

Mae Aida

et al.

GeroScience, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

Language: Английский

Citations

5
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

4
Noradrenergic alterations associated with early life stress DOI Creative Commons

M Sheppard,

Jalil Rasgado‐Toledo, Niall W. Duncan

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 164, P. 105832 - 105832

Published: July 29, 2024

Significant stress in childhood or adolescence is linked to both structural and functional changes the brain human analogous animal models. In addition, neuromodulators, such as noradrenaline (NA), show life-long alterations response these early life stressors, which may impact upon sensitivity time course of key adrenergic activities, rapid autonomic responses (the 'fight flight response'). The locus-coeruleus noradrenergic (LC-NA) network, a stress-responsive network brain, displays numerous significant early- stress. Here, we review relationship between NA neurobiological associated with set out future lines research that can illuminate how circuits circulating neurotransmitters adapt stressors.

Language: Английский

Citations

4
Differential gray matter correlates and machine learning prediction of abuse and internalizing psychopathology in adolescent females DOI Creative Commons
Sara A. Heyn, Taylor J. Keding, Josh M. Cisler

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 3, 2025

Childhood abuse represents one of the most potent risk factors for development psychopathology during childhood, accounting 30–60% onset. While previous studies have separately associated reductions in gray matter volume (GMV) with childhood and internalizing (IP), it is unclear whether IP differ their structural abnormalities, which GMV features are related to at individual level. In a pooled multisite, multi-investigator sample, 246 child adolescent females between ages 8–18 were recruited into interpersonal violence (IPV) and/or (i.e. posttraumatic stress disorder (PTSD), depression, anxiety). Youth completed assessments IP, history, underwent high resolution T1 MRI. First, we characterized how differences exposure depend on presence or absence using voxel-based morphometry (VBM). Next, trained convolutional neural networks predict experience estimated strength direction importance each feature making individual-level predictions Shapley values. values aggregated across entire cohort, top 1% clusters highest reported. At group-level, VBM analyses identified widespread decreases prefrontal cortex, insula, hippocampus youth while was specifically increased cingulate cortex supramarginal gyrus. Further, interactions severity ventral dorsal anterior thalamus. After extensive training, model tuning, evaluation, performed above chance when predicting (63% accuracy) experiences (71% level individual. Interestingly, regions had degree overlap group-level patterns. We unique correlates both group overlap, providing evidence that trauma may uniquely jointly impact neurodevelopment. Feature learning offer power novelty beyond traditional approaches identification biomarkers movement towards individualized diagnosis treatment.

Language: Английский

Citations

0
Resting-state electroencephalographic rhythms depend on sex in patients with dementia due to Parkinson's and Lewy Body diseases: An exploratory study DOI Creative Commons
Claudio Del Percio, Roberta Lizio, Susanna Lopez

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106807 - 106807

Published: Jan. 1, 2025

Parkinson's disease with dementia (PDD) and Lewy bodies (DLB) are more prevalent in males than females. Furthermore, they typically showed abnormally high delta (< 4 Hz) low alpha (8-10 rhythms from resting-state electroencephalographic (rsEEG) activity. Here, we hypothesized that those abnormalities may depend on the patient's sex. An international database provided clinical-demographic-rsEEG datasets for cognitively unimpaired older (Healthy; N = 49; 24 females), PDD (N 39; 13 DLB 38; 15 females) participants. Each group was stratified into matched female male subgroups. The rsEEG were investigated across individual delta, theta, frequency bands based peak. eLORETA freeware used to estimate cortical sources. In Healthy group, widespread source activities greater females males. lower central-parietal lower, posterior These results suggest sex-dependent hormonal modulation of neuroprotective-compensatory neurophysiological mechanisms patients underlying generation rhythms, which should be considered treatment vigilance dysregulation patients.

Language: Английский

Citations

0
Attention-dependent coupling with forebrain and brainstem neuromodulatory nuclei differs across the lifespan DOI Creative Commons
Nicholas G. Cicero, Elizabeth Riley, Khena M. Swallow

et al.

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

Published: March 4, 2025

Attentional states reflect the changing behavioral relevance of stimuli in one's environment, having important consequences for learning and memory. Supporting well-established cortical contributions, attentional are hypothesized to originate from subcortical neuromodulatory nuclei, such as basal forebrain (BF) locus coeruleus (LC), which among first change with aging. Here, we characterized interplay between BF LC nuclei their relation two common afferent targets attention memory, posterior cingulate cortex hippocampus, across adult lifespan. Using an auditory target discrimination task during functional MRI, examined influence salience on task-dependent connectivity younger (19-45 years) older adults (66-86 years). In adults, was largely driven by processing, while associated distractor processing. These patterns reversed adults. This age-dependent pattern generalized nucleus basalis Meynert medial septal subnuclei. Preliminary data middle-aged indicates a transitional stage connectivity. Overall, these results reveal distinct roles systems related potential aging, consistent managing increased behaviorally irrelevant distraction Such prominent differences coupling lifespan suggests they may be drivers widespread changes neurocognitive middle age opportune time intervention.

Language: Английский

Citations

0
Epigallocatechin -3- gallate mitigates diazinon neurotoxicity via suppression of pro-inflammatory genes and upregulation of antioxidant pathways DOI Creative Commons

Charles Etang Onukak,

Omowumi Femi‐Akinlosotu, Adedunsola A. Obasa

et al.

BMC Neuroscience, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 10, 2025

Diazinon is a commonly used organophosphate (OP) insecticide especially in developing countries for the control of insect pests, however, exposure to its toxic impact humans and other non-target species remains an important public health concern. The study aimed investigate effect epigallocatechin -3- gallate (EGCG), abundant green tea plants on neurobehavioural, biochemical, pathological changes brain male Wistar rats following diazinon toxicity. Sixty adult were acclimatized seven days subsequently randomly assigned into six treatment groups as follows: Group I: Control group (0.2 mL distilled water); II: at 3 mg/kg (1% LD50); III: (3 mg/kg) + EGCG (50 mg/kg, ~ 2% IV: (100 5% V: VI: mg/kg). All treatments administered orally once daily 14 days. Neurobehavioural studies, biomarkers oxidative stress, histology, immunohistochemistry, quantitative polymerase chain reaction (RT qPCR) performed. alone impaired recognition memory, increased stress markers altered antioxidant defense brain. It upregulated TNF-α IL-6 genes repressed GPx 4 gene expressions. was also associated with GFAP, Tau, α-SN immunoreactivity. Microscopic examination revealed loss Purkinje hippocampal cells Co-treatment however improved cognition, lowered markers, status suppressed IL-6. In conclusion, findings from this demonstrated that offered protection against diazinon-induced neurotoxicity. Hence, natural sources such fruits vegetables could offer immense benefits by protecting inflammation neurodegenerative disease conditions. Clinical trial number Not applicable.

Language: Английский

Citations

0