Integrated Transcriptomics and Network Analysis Identified Altered Neural Mechanisms in Frontal Aging Brain-Associated Alzheimer’s Disease DOI
Suthipong Chujan, Wanida Cholpraipimolrat, Jutamaad Satayavivad

et al.

Biochemical Genetics, Journal Year: 2023, Volume and Issue: 62(4), P. 2382 - 2398

Published: Nov. 7, 2023

Language: Английский

Disrupted spatial and contextual memory encoding in the hippocampus of 5xFAD mice precedes cognitive impairment DOI Creative Commons
Yimei Li,

Mary Ann T. Go,

Hualong Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Abstract Alzheimer’s disease (AD) is marked by progressive cognitive decline, yet the underlying neural mechanisms are not fully understood. To address this, we investigated hippocampal activity in 5xFAD model mice performing a continuous spatial alternation task, combining behavioural assessment with vivo two-photon calcium imaging. Young exhibited mild performance deficits, which worsened age. Older showed significant impairments task acquisition and accuracy, hyperactivity. Hippocampal CA1 neurons early representation, prior to showing deficits. Both young old reduced tuning, fewer place cells, decreased trial-to-trial reliability comparison wildtype sibling controls. Additionally, demonstrated disrupted encoding of reward locations, correlation between correct error trials. Analysis “splitter” cells revealed splitting mice, discriminability trajectory-dependent activity. These deficits correlated poorer performance, suggesting that contextual contributes decline AD. Our findings highlight disruptions precede provide insights into AD pathophysiology. Teaser Two-photon imaging behaving reveals memory circuits

Language: Английский

Citations

0
Repetitive prefrontal tDCS activates VTA dopaminergic neurons, resulting in attenuation of Alzheimer’s Disease-like deficits in Tg2576 mice DOI Creative Commons

Maria Luisa De Paolis,

Gilda Loffredo,

Paraskevi Krashia

et al.

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 29, 2025

Language: Английский

Citations

0
Targeting dopamine transporter to ameliorate cognitive deficits in Alzheimer's disease DOI Creative Commons
Ammara Shaikh, Fairus Ahmad, Seong Lin Teoh

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Nov. 13, 2023

Alzheimer's disease (AD) is characterized by the pathologic deposition of amyloid and neurofibrillary tangles in brain, leading to neuronal damage defective synapses. These changes manifest as abnormalities cognition behavior. The functional deficits are also attributed multiple neurotransmitter systems contributing dysfunction. One such important system dopaminergic system. It plays a crucial role modulating movement, cognition, behavior while connecting various brain areas influencing other systems, making it relevant neurodegenerative disorders like AD Parkinson's (PD). Considering its significance, has emerged promising target for alleviating movement cognitive PD AD, respectively. Extensive research been conducted on neurons, receptors, dopamine levels critical factors memory AD. However, exact nature features extrapyramidal symptoms not fully understood yet Recently, previously overlooked element system, transporter, shown significant promise more effective enhancing addressing dysfunction

Language: Английский

Citations

10
VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction DOI Creative Commons
Harris E. Blankenship,

Kelsey A Carter,

Kevin D. Pham

et al.

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

Published: Nov. 8, 2024

Abstract Alzheimer’s disease (AD) patients exhibit neuropsychiatric symptoms that extend beyond classical cognitive deficits, suggesting involvement of subcortical areas. Here, we investigated the role midbrain dopamine (DA) neurons in AD using amyloid + tau-driven 3xTg-AD mouse model. We found deficits reward-based operant learning mice, possible VTA DA neuron dysregulation. Physiological assessment revealed hyperexcitability and disrupted firing caused by reduced activity small-conductance calcium-activated potassium (SK) channels. RNA sequencing from contents single patch-clamped (Patch-seq) identified up-regulation SK channel modulator casein kinase 2 (CK2), which corroborated immunohistochemical protein analysis. Pharmacological inhibition CK2 restored normal patterns mice. These findings identify a mechanism ion dysregulation could contribute to behavioral abnormalities AD, paving way for novel treatment strategies.

Language: Английский

Citations

3
Pathogenesis of Depression in Alzheimer’s Disease DOI

Qingyang Zhan,

Fanyi Kong, Shuai Shao

et al.

Neurochemical Research, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 28, 2023

Language: Английский

Citations

5
Brain structural alterations in internet gaming disorder: Focus on the mesocorticolimbic dopaminergic system DOI

Mingyuan Tian,

Xinyi Zhou,

Xiao-Yuan Liao

et al.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2023, Volume and Issue: 127, P. 110806 - 110806

Published: June 3, 2023

Language: Английский

Citations

4
Impairment of hippocampal astrocyte-mediated striatal dopamine release and locomotion in Alzheimer's disease DOI Creative Commons
Benjamin B. Tournier, Kelly Ceyzériat, Aurélien M. Badina

et al.

NeuroImage, Journal Year: 2024, Volume and Issue: 298, P. 120778 - 120778

Published: Aug. 8, 2024

Language: Английский

Citations

1
Artificial intelligence–assisted oculo‐gait measurements for cognitive impairment in cerebral small vessel disease DOI Creative Commons
Huimin Chen, Hao Du, Fang Yi

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract INTRODUCTION Oculomotor and gait dysfunctions are closely associated with cognition. However, oculo‐gait patterns their correlation cognition in cerebral small vessel disease (CSVD) remain unclear. METHODS Patients CSVD from a hospital‐based cohort ( n = 194) individuals presumed early community‐based 319) were included. Oculo‐gait measured using the artificial intelligence (AI) –assisted ‘EyeKnow’ eye‐tracking ‘ReadyGo’ motor evaluation systems. Multivariable linear logistic regression models employed to investigate association between parameters RESULTS Anti‐saccade accuracy, stride velocity, swing velocity significantly both patients community dwellers CSVD, could identify cognitive impairment moderate accuracy (area under curve [AUC]: hospital cohort, 0.787; 0.810) after adjusting for age education. DISCUSSION The of features (anti‐saccade velocity) may help screen CSVD. Highlights (lower anti‐saccade (CSVD). Logistic model integrating features, age, education level moderately distinguished status Artificial intelligence–assisted oculomotor measurements provide quick accurate settings.

Language: Английский

Citations

1
Dopaminergic deficits along the spectrum of Alzheimer’s Disease DOI Creative Commons
Andrea Pilotto, Alice Galli, Arianna Sala

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Abstract Both post-mortem and in vivo data argue for dopamine dysfunction patients with Alzheimer’s Disease (AD). However, the timing regional progression of dopaminergic systems alterations AD are still debated. Aim study was to investigate pattern changes connectivity using DAT-SPECT imaging across spectrum. Fifty-nine A + T N (n = 21 MCI-AD; n 38 AD-DEM) 45 age sex-matched controls (CG) entered underwent 123I-FP-CIT imaging. The occipital binding used as reference region obtain single-subject different brain regions. Between-groups differences both mesolimbic nigrostriatal pathways were assessed an ANCOVA test-adjusting effect center acquisition, age, sex. Regions resulting from voxel-wise direct comparison between MCI-AD AD-DEM considered a seed interest interregional correlation analysis. showed depletion within basal ganglia, whereas cortico-limbic regions (namely hippocampus, amygdala, anterior middle cingulate, frontal cortex thalamus) resulted impaired only dementia phase. analysis progressive disruption caudate/thalamus hippocampus amygdala stages. This indicates ganglia already early stage AD, extending several phases.

Language: Английский

Citations

0
State of the Art in Sub-Phenotyping Midbrain Dopamine Neurons DOI Creative Commons

Valentina Basso,

Máté D. Döbrössy, Lachlan H. Thompson

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(9), P. 690 - 690

Published: Sept. 3, 2024

Dopaminergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNpc) comprise around 75% of all dopaminergic human brain. While both groups are close proximity midbrain partially overlap, development, function, impairments these two classes highly diverse. The molecular cellular mechanisms underlying differences not yet fully understood, but research over past decade has highlighted need to differentiate between during their development mature This differentiation is crucial only for understanding fundamental circuitry formation brain also developing therapies targeted specific neuron without affecting others. In this review, we summarize state art our VTA SNpc, such as anatomy, structure, morphology, output input, electrophysiology, disorders, discuss current technologies methods available studying neurons, highlighting advantages, limitations, necessary improvements required achieve more-precise therapeutic interventions.

Language: Английский

Citations

0