Characterization of the expression and function of schizophrenia risk gene Dtnbp1 in the suprachiasmatic nucleus
Bibliographic record
Abstract
Schizophrenia (SZ) is a debilitating neurodevelopmental disorder with environmental and genetic origins. Circadian rhythm disruption is observed in a large proportion of patients with SZ. We previously found that Sandy (Sdy) mice, which carry a mutation in the SZ-associated gene dystrobrevin binding protein 1 (Dtnbp1, also called Dysbindin-1), show altered rhythms of locomotor activity. To address the possible mechanisms underlying the circadian phenotype of these mice, we set out to address the expression and function of Dtnbp1 in the suprachiasmatic nucleus (SCN), the location of the central circadian clock in mammals. Immunohistochemistry revealed that DTNBP1 protein was expressed throughout the SCN, with stronger expression in the dorsal part. DTNBP1 immunoreactive signal colocalized with neurons expressing either arginine vasopressin peptide (AVP) or vasoactive intestinal peptide (VIP). Fluorescent in situ hybridization showed a time-dependent variation of expression of Dtnbp1 transcript, and confirmed its location in cell bodies of AVP- and VIP-expressing cells. Since DTNBP1 is known to be implicated in synaptic transmission, we studied the effect of Dtnbp1 gene mutation on SCN neuropeptide expression and neuroanatomy in Sdy mice. There was no significant effect of the Dtnbp1 mutation on AVP and VIP expression in the SCN. We then used transmission electron microscopy to study synaptic morphology and secretory vesicles. There was no effect of the Dtnbp1 mutation on these neuroanatomical features. Our data show that Dtnbp1 is expressed with a daily rhythm across the SCN, but that a loss-of-function mutation did not impair AVP or VIP neuropeptide expression nor general synaptic architecture.
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 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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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".