The Impact of Methylenetetrahydrofolate Reductase (MTHFR) Deficiency in a Paraquat Mouse Model of Parkinson’s Disease
Bibliographic record
Abstract
The cause of Parkinson's disease (PD) remains unknown.Environmental toxicants such as paraquat have been linked to the characteristic dopaminergic (DA) neurodegeneration in the substantia nigra (SN); nutrition may also play a role.A common polymorphism (677CàT) in methylenetetrahydrofolate reductase (MTHFR), a folic acid metabolism enzyme, is associated with increased PD incidence.Using a mouse model that mimics this polymorphism, this study aimed to determine whether MTHFR deficiency leads to enhanced degeneration in a paraquat PD model.Male 3-month-old Mthfr +/+ and Mthfr +/-mice received paraquat or saline injections.Mthfr +/-mice demonstrated motor and a trend for memory impairment compared to Mthfr +/+ mice.No differences in SN DA neuron numbers or antioxidant activity were seen, however, increased oxidative stress and antioxidant activity were observed within the dorsal striatum of Mthfr +/-mice.These results suggest potential enhanced vulnerability to paraquat due to MTHFR deficiency through changes in such processes within this region.v Neuroinflammation Homocysteine: plasma concentrations and levels in the brain Antioxidant activity Gp91 SOD2 Protein levels of α-synuclein Methylation Discussion Increased oxidative stress and homocysteine levels in striatum may provide information regarding timing of disease progression No difference in total α-synuclein may not account for all possible changes in the protein Effect of MTHFR deficiency and paraquat on methylation Conclusions Future directions vi List of Abbreviations 5-HT -serotonin 6-OHDA -6-hydroxydopamine AAV -adeno-associated virus AD -Alzheimer's disease ANOVA -analysis of variance BHMT -betaine homocysteine methyltransferase BSA -bovine serum albumin CD68 -cluster of differentiation 68 CI -confidence interval DA -dopaminergic DAB -diaminobenzidine DAPI -4',6-diamidino-2-phenylindole DHF -dihydrofolate dTMP -deoxythymidine monophosphate dUMP -deoxyuridine monophosphate GAPDH -glyceraldehyde 3-phosphate dehydrogenase Gp91 -gp91 phox subunit of NADPH oxidase HPLC -high-performance liquid chromatography HRP -horseradish peroxidase Iba1 -ionized calcium-binding adapter molecule 1 i.p. -intraperitoneal LC -locus coeruleus L-DOPA -levodopa LPS -lipopolysaccharide LRRK2 -leucine-rich repeat kinase 2 MAT2A -methionine adenosyltransferase 2A mPFC -medial prefrontal cortex MPP + -1-methyl-4-phenylpyridinium MPTP -1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine MS -methionine synthase MTHFR -methylenetetrahydrofolate reductase NADPH-nicotinamide adenine dinucleotide phosphate NE -norepinephrine NGS -normal goat serum OR -odds ratio PBS -phosphate buffered saline PD -Parkinson's disease PFC -prefrontal cortex PHOX -p47 phox-/- PINK1 -PTEN-induced putative kinase 1 PVN -paraventricular nucleus ROS -reactive oxygen species SAM -S-adenosylmethionine SAH -S-adenosylhomocysteine
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".