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Record W4394979911 · doi:10.1007/s12035-024-04161-0

Dose-Ranging Effects of the Intracerebral Administration of Atsttrin in Experimental Model of Parkinson’s Disease Induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Mice

2024· article· en· W4394979911 on OpenAlexfundno aff
Łukasz A. Poniatowski, Ilona Joniec‐Maciejak, Adriana Wawer, Anna Sznejder-Pachołek, Ewa Machaj, Katarzyna Ziętal, Dagmara Mirowska-Guzeł

Bibliographic record

VenueMolecular Neurobiology · 2024
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsnot available
FundersEuropean Regional Development FundNYU Grossman School of MedicineUniwersytet WarszawskiEuropean CommissionWarszawski Uniwersytet MedycznyYork UniversityYale University
KeywordsMPTPNeurochemicalParkinson's diseaseSubstantia nigraDopaminergicMedicineStriatumNeurodegenerationNeurologyDiseaseDopaminePharmacologyNeuroscienceInternal medicinePsychology

Abstract

fetched live from OpenAlex

Parkinson's disease is one of the most common neurodegenerative disorders characterized by a multitude of motor and non-motor clinical symptoms resulting from the progressive and long-lasting abnormal loss of nigrostriatal dopaminergic neurons. Currently, the available treatments for patients with Parkinson's disease are limited and exert only symptomatic effects, without adequate signs of delaying or stopping the progression of the disease. Atsttrin constitutes the bioengineered protein which ultrastructure is based on the polypeptide chain frame of the progranulin (PGRN), which exerts anti-inflammatory effects through the inhibition of TNFα. The conducted preclinical studies suggest that the therapeutic implementation of Atsttrin may be potentially effective in the treatment of neurodegenerative diseases that are associated with the occurrence of neuroinflammatory processes. The aim of the proposed study was to investigate the effect of direct bilateral intracerebral administration of Atsttrin using stereotactic methods in the preclinical C57BL/6 mouse model of Parkinson's disease inducted by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. The analysis of the dose dependency effects of the increasing doses of Atsttrin has covered a number of parameters and markers regarding neurodegenerative processes and inflammatory responses including IL-1α, TNFα, IL-6, TH, and TG2 mRNA expressions. Accordingly, the evaluation of the changes in the neurochemical profile included DA, DOPAC, 3-MT, HVA, NA, MHPG, 5-HT, and 5-HIAA concentration levels. The intracerebral administration of Atsttrin into the striatum effectively attenuated the neuroinflammatory reaction in evaluated neuroanatomical structures. Furthermore, the partial restoration of monoamine content and its metabolic turnover were observed. In this case, taking into account the previously described pharmacokinetic profile and extrapolated bioavailability as well as the stability characteristics of Atsttrin, an attempt was made to describe as precisely as possible the quantitative and qualitative effects of increasing doses of the compound within the brain tissue microenvironment in the presented preclinical model of the disease. Collectively, this findings demonstrated that the intracerebral administration of Atsttrin may represent a potential novel therapeutic method for the treatment of Parkinson's disease.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.025
Threshold uncertainty score0.657

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.266
Teacher spread0.255 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2024
Admission routes1
Has abstractyes

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