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Record W3186203970 · doi:10.22215/etd/2020-14426

Immunohistochemical characterization of GluN2 NMDA receptor subunit expression in the dorsal horn of rats and humans

2020· dissertation· en· W3186203970 on OpenAlexaff
Santa Temi

Bibliographic record

Venuenot available
Typedissertation
Languageen
FieldMedicine
TopicPain Mechanisms and Treatments
Canadian institutionsCarleton University
Fundersnot available
KeywordsNMDA receptorSpinal cordGlutamate receptorNeuroscienceImmunohistochemistryProtein subunitReceptorLumbar Spinal CordBiologyDorsumInternal medicineCell biologyEndocrinologyAnatomyMedicineImmunologyGeneticsGene

Abstract

fetched live from OpenAlex

NMDA receptors (NMDARs) are excitatory ionotropic glutamate receptors expressed throughout the CNS, including in the superficial dorsal horn (SDH) of the spinal cord.The GluN2 subtypes of NMDAR subunit, GluN2A, GluN2B and GluN2D, confer NMDARs with structural and functional variability, enabling heterogeneity in synaptic transmission and plasticity.Despite essential roles for NMDARs in physiological and pathological pain processing within the SDH, the distribution and function of specific GluN2 isoforms across SDH laminae remains poorly understood.Surprisingly, there is a complete lack of knowledge on GluN2 expression in female rodent or human spinal cord.In this study we therefore aimed to investigate the relative expression of specific GluN2 variants in the L4/L5 lumbar SDH of both male and female rats and humans.To detect synaptic GluN2 isoforms that are expressed in the SDH (GluN2A, 2B and 2D), we used a spinal cord immunohistochemistry approach combined with pepsin antigen-retrieval to unmask these highly cross-linked protein complexes.We found a dominant expression of both GluN2B and GluN2D subunits in the SDH of male rats, while only GluN2B was preferentially localized to the SDH of females.Surprisingly, we also identified that the GluN2B NMDAR subtype was more abundantly expressed in the medial compared to the lateral, but in male rats only.Finally, we successfully adapted the staining approaches from rodent to human spinal tissue in order to investigate whether the specific expression patterns for NMDAR GluN2 subtypes are conserved in the human SDH in future studies.These specific localization patterns of GluN2-NMDARs subtypes to pain-processing regions of the SDH has important implications for both the understanding and treatment of pain.Expression of NMDAR subunits in the dorsal horn of rats and humans iii Acknowledgments I would like to express my gratitude to my supervisor, Dr. Michael Hildebrand, for his dedicated guidance and support throughout this project.A huge thank you also for having revised and provided insightful feedback to this thesis.I would like to thank Dr. Chris Rudyk who collaborated on this project and took care of the confocal image acquisition.Thank you for the encouragement during critical moments

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.013
GPT teacher head0.274
Teacher spread0.261 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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

Citations0
Published2020
Admission routes1
Has abstractyes

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