Exploratory Study of Gastrointestinal Redox Biomarkers in the Presymptomatic and Symptomatic Tg2576 Mouse Model of Familial Alzheimer’s Disease: Phenotypic Correlates and Effects of Chronic Oral d-Galactose DOI Creative Commons
Jan Homolak, Ana Babić Perhoč, Ana Knezović

et al.

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(22), P. 4013 - 4025

Published: Nov. 6, 2023

The gut might play an important role in the etiopathogenesis of Alzheimer's disease (AD) as gastrointestinal alterations often precede development neuropathological changes brain and correlate with progression animal models. has immense capacity to generate free radicals whose AD is well-known; however, it remains be clarified whether redox homeostasis associated AD. aim was (i) examine presymptomatic symptomatic Tg2576 mouse model AD; (ii) investigate effects oral d-galactose previously shown alleviate cognitive deficits metabolic models reduce oxidative stress; (iii) association between biomarkers behavioral mice. In stage, mice displayed increased electrophilic tone, characterized by higher lipid peroxidation elevated Mn/Fe-SOD activity. these are rectified, but total antioxidant decreased. Chronic reduced had opposite wild-type animals. tract greater spatial memory. Gut involved pathophysiology should further explored this context.

Language: Английский

The Absence of Gastrointestinal Redox Dyshomeostasis in the Brain-First Rat Model of Parkinson’s Disease Induced by Bilateral Intrastriatal 6-Hydroxydopamine DOI Creative Commons
Jan Homolak, Mihovil Joja, Gracia Grabarić

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(8), P. 5481 - 5493

Published: Jan. 10, 2024

The gut-brain axis plays an important role in Parkinson's disease (PD) by acting as a route for vagal propagation of aggregated α-synuclein the gut-first endophenotype and mediator gastrointestinal dyshomeostasis via nigro-vagal pathway brain-first disease. One mechanism which may promote PD is regulating redox homeostasis overwhelming evidence suggests that oxidative stress key etiopathogenesis progression tract maintains organism critical barrier to environmental microbiological electrophilic challenges. present aim was utilize bilateral intrastriatal 6-hydroxydopamine (6-OHDA) model study effects isolated central pathology on tract. Three-month-old male Wistar rats were either not treated (intact controls; CTR) or bilaterally intrastriatally with vehicle (CIS) 6-OHDA (6-OHDA). Motor deficits assessed rotarod performance test, duodenum, ileum, colon dissected biochemical analyses 12 weeks after treatment. Lipid peroxidation, total antioxidant capacity, low-molecular-weight thiols, protein sulfhydryls, activity Mn/Fe superoxide dismutases, azide-insensitive catalase/peroxidase measured. Both univariate multivariate models analyzing biomarkers indicate significant disturbances balance are present. findings demonstrate motor impairment observed can occur without concurrent imbalances system.

Language: Английский

Citations

5
Insights into Gastrointestinal Redox Dysregulation in a Rat Model of Alzheimer’s Disease and the Assessment of the Protective Potential of D-Galactose DOI Creative Commons
Jan Homolak, Konstantinos Varvaras,

Vittorio Sciacca

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(10), P. 11288 - 11304

Published: Feb. 27, 2024

Recent evidence suggests that the gut plays a vital role in development and progression of Alzheimer's disease (AD) by triggering systemic inflammation oxidative stress. The well-established rat model AD, induced intracerebroventricular administration streptozotocin (STZ-icv), provides valuable insights into GI implications neurodegeneration. Notably, this leads to pathophysiological changes gut, including redox dyshomeostasis, resulting from central neuropathology. Our study aimed investigate mechanisms underlying dyshomeostasis assess effects D-galactose, which is known benefit homeostasis alleviate cognitive deficits model. Duodenal rings isolated STZ-icv animals control groups were subjected prooxidative environment using 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) or H2O2 with without D-galactose oxygenated Krebs buffer ex vivo. Redox was analyzed through protein microarrays functional biochemical assays alongside cell survival assessment. Structural equation modeling univariate multivariate models employed evaluate differential response samples controlled challenge. showed suppressed expression catalase glutathione peroxidase 4 (GPX4) increased baseline activity enzymes involved superoxide homeostasis. altered status associated an inability respond challenges D-galactose. Conversely, presence antioxidant capacity, enhanced activity, upregulated dismutases samples. STZ-icv-induced dysfunction characterized diminished ability regulatory system maintain long-term protection transcription genes as well compromised activation responsible for immediate defense. can exert beneficial on under physiological conditions.

Language: Английский

Citations

2
Association of Cognitive Deficit with Glutamate and Insulin Signaling in a Rat Model of Parkinson’s Disease DOI Creative Commons
Ana Knezović,

Marija Piknjac,

Jelena Osmanović Barilar

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(3), P. 683 - 683

Published: Feb. 23, 2023

Cognitive deficit is a frequent non-motor symptom in Parkinson's disease (PD) with an unclear pathogenesis. Recent research indicates possible involvement of insulin resistance and glutamate excitotoxicity PD development. We investigated cognitive performance the brain signaling rat model induced by bilateral intrastriatal injection 6-hydroxydopamine (6-OHDA). functions were assessed Passive Avoidance (PA) Morris Water Maze (MWM) tests. The expression tyrosine hydroxylase (TH) proteins involved (insulin receptor - IR, phosphoinositide 3 kinase pI3K, extracellular signal-regulated kinases-ERK) (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptos-AMPAR, N-methyl-D-aspartate NMDAR) was hippocampus (HPC), hypothalamus (HPT) striatum (S) immunofluorescence, Western blot enzyme-linked immunosorbent assay (ELISA). Three months after 6-OHDA treatment, accompanied decreased AMPAR activity TH levels (HPC, S), while remained largely unchanged. Spearman's rank correlation revealed strong positive for pAMPAR-PA (S), pNMDAR-pI3K (HPC) pNMDAR-IR (all regions). Additionally, found TH-ERK TH-pI3K, negative one TH-MWM/errors pI3K-MWM/time (S). These results suggest association between (but not insulin) dysfunction model, detected three treatment.

Language: Английский

Citations

5
Unveiling the Journey from the Gut to the Brain: Decoding Neurodegeneration–Gut Connection in Parkinson’s Disease DOI
Kritika Bhardwaj, Aditya A. Singh, Hemant Kumar

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(13), P. 2454 - 2469

Published: June 19, 2024

Parkinson's disease, a classical motor disorder affecting the dopaminergic system of brain, has been as disease but this notion now viewed differently pathology begins in gut and then gradually moves up to brain regions. The microorganisms play critical role maintaining physiology from barrier integrity secretion microbial products that maintain healthy state. subsequently alters normal composition microbes causes deleterious effects ultimately trigger strong neuroinflammation nonmotor symptoms along with characteristic synucleopathy, pathological hallmark disease. Understanding complex pathomechanisms distinct established preclinical models is primary goal researchers decipher how exactly central effect; quest led many answered some open-ended questions for researchers. We summarize popular opinions contrasting views, concise footsteps treatment strategies targeting gastrointestinal system.

Language: Английский

Citations

1
Exploratory Study of Gastrointestinal Redox Biomarkers in the Presymptomatic and Symptomatic Tg2576 Mouse Model of Familial Alzheimer’s Disease: Phenotypic Correlates and Effects of Chronic Oral d-Galactose DOI Creative Commons
Jan Homolak, Ana Babić Perhoč, Ana Knezović

et al.

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(22), P. 4013 - 4025

Published: Nov. 6, 2023

The gut might play an important role in the etiopathogenesis of Alzheimer's disease (AD) as gastrointestinal alterations often precede development neuropathological changes brain and correlate with progression animal models. has immense capacity to generate free radicals whose AD is well-known; however, it remains be clarified whether redox homeostasis associated AD. aim was (i) examine presymptomatic symptomatic Tg2576 mouse model AD; (ii) investigate effects oral d-galactose previously shown alleviate cognitive deficits metabolic models reduce oxidative stress; (iii) association between biomarkers behavioral mice. In stage, mice displayed increased electrophilic tone, characterized by higher lipid peroxidation elevated Mn/Fe-SOD activity. these are rectified, but total antioxidant decreased. Chronic reduced had opposite wild-type animals. tract greater spatial memory. Gut involved pathophysiology should further explored this context.

Language: Английский

Citations

2