Role of Synapsin II in Neurodevelopment: Delineating the Role of Developmental Medial Prefrontal Cortical Synapsin II Reductions in the Pathophysiology of Schizophrenia
Bibliographic record
Abstract
Synapsins are primarily neuron-specific proteins critical for neurotransmission, synaptogenesis and synapse maintenance. Synapsin II has been specifically linked with increased susceptibility towards developing schizophrenia. Reduced synapsin II mRNA levels were found in the dorsolateral prefrontal cortex (PFC) of patients with schizophrenia. Moreover, synapsin II knockdown in the medial PFC (mPFC) of the adult rat was previously shown to cause schizophrenia-like behaviour and altered expression levels of vesicular proteins involved in glutamatergic and GABAergic signaling within the mPFC. The study of schizophrenia in recent years has shifted to focus on neurodevelopmental players which influence disease outcome. This study was designed to establish the link between neurodevelopmental dysregulation of synapsin II and schizophrenia. Specific knockdown of synapsin II was performed in the mPFC at postnatal day (PD) 7 and PD 17-23. Schizophrenia-like behavioural abnormalities were assessed at pre-pubertal (PD 32-35) and post-pubertal (PD 65-70) stages. Protein estimation of vesicular transporters involved in glutamate, GABA, and dopamine neurotransmitter systems were also assessed in the mPFC. Results from this study indicate (1) synapsin II knockdown during PD 17-23, but not PD 7, caused lasting schizophrenia-like abnormalities (2) abnormalities exhibited permanence at pre-pubertal and post-pubertal stages, and manifested as a function of brain development, (3) behavioural abnormalities were reminiscent of symptoms in established animal models of schizophrenia (i.e. deficits in prepulse inhibition, social withdrawal, locomotor hyperactivity), (4) neurodevelopmental synapsin II alterations induced hypoactive glutamatergic activity through decreased synapsin IIa expression levels (pre-pubertal) and decreased VGLUT-2 expression levels (post-pubertal), and (5) acute olanzapine treatment effectively attenuated schizophrenia-like abnormalities through normalized synapsin IIa expression levels (pre-pubertal) and increased GAD65/67 expression levels (post-pubertal). Results show the causal link between synapsin II expression during critical neurodevelopmental stages and schizophrenia. Additionally, evidence has been provided for the face, construct, and predictive validities of this newly developed animal model of schizophrenia.
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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) | 0.000 | 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".