Cross-Cutting Themes

What are microglia and where do they originate from?

Microglia are tissue-resident macrophages in the CNS originating from the yolk sac during early embryogenesis.

What percentage do microglia represent in the mouse brain?

Microglia represent 5-12% of glial cells in the mouse brain.

How do microglia maintain their population?

Microglia maintain their population through self-renewal rather than infiltration from the periphery.

What happens to microglial numbers at disease-related brain insults?

Microglial numbers increase due to the proliferation of brain resident microglia.

What role do microglia play if the blood-brain barrier is damaged?

They recruit peripheral monocytes and macrophages.

What experimental methods are used to deplete microglia?

Genetic methods (like inducing toxins) and pharmacological methods (like CSF-1 antagonists).

What is the time frame for microglial repopulation after depletion?

Microglia repopulate the brain within 3-5 days after depletion.

What are the key functions of microglia in the brain?

Surveillance, phagocytosis, synaptic pruning, plasticity, and neurogenesis.

How do microglia contribute to synaptic pruning?

Microglia eliminate redundant synapses during development, shaping neural circuits.

What impact do neurodegenerative disorders have on microglia?

They can prolong microglial activation, leading to further neuronal or glial cell death.

What are the negative symptoms of schizophrenia?

Negative symptoms include anhedonia and lack of motivation.

What is the significance of the gene CYFIP1 in schizophrenia?

It regulates cytoskeletal dynamics and is associated with neural development and rosette formation.

What is the mechanism of CRISPR/Cas9 in gene editing?

It creates double-stranded DNA breaks, which can be repaired via NHEJ or HDR.

What are antipsychotics primarily used for?

Antipsychotics are mainly used to treat positive symptoms of schizophrenia, like delusions and hallucinations.

What findings suggest a dysregulation of microglia in schizophrenia?

Post-mortem studies show mixed findings on microglial activation in schizophrenia brains.

What is the 'two-hit' hypothesis related to microglia?

It states that perinatal stress primes microglia for hyperactive pruning later in life.

What are the effects of chronic antipsychotic treatment on microglia?

Chronic treatment increases IBA1+ microglia and alters their morphology.

What are the limitations of current antipsychotic treatments in schizophrenia?

They primarily target positive symptoms and have side effects, leaving many patients symptomatic.

What role does the complement system play in synaptic pruning?

C4 activates complement C3, tagging synapses for removal by microglial CR3.

How do iPSC models help in studying schizophrenia?

iPSCs allow the study of patient-specific synaptic abnormalities and genetic editing.

What did the Brennand et al. (2010) study find regarding iPSCs and schizophrenia?

It revealed that iPSCs cannot visualize all aspects of schizophrenia pathology.

What is a limitation of animal models in schizophrenia research?

They do not fully recapitulate the human disease complexity.

How do dendritic spines function in the brain?

Dendritic spines are crucial for synaptic transmission and plasticity.

What challenges does gene editing face in modeling polygenic conditions?

Gene editing is time-consuming, and interpretation can be complicated by variability across lines.

What are the emerging treatments mentioned for schizophrenia?

Immune-targeting drugs, such as minocycline and monoclonal antibodies, are in trials.

What findings do animal studies suggest about microglial activity and schizophrenia?

They suggest that chronic antipsychotic treatment may increase microglial activity.

What does GWAS stand for and its relevance in schizophrenia?

Genome-Wide Association Studies identify loci implicated in schizophrenia.

What significance does post-mortem tissue analysis have in understanding microglia?

It provides insights into changes in microglial activation in various conditions.

How are synaptic impairments related to cognitive deficits in schizophrenia?

Alterations in spine functionality disrupt normal neural information flow, leading to cognitive deficits.

What is the role of cytokines in the context of schizophrenia?

Studies suggest increased levels of pro-inflammatory cytokines in patients with schizophrenia.