Cellular Basis of Behavioural Illness Flashcards
What are the general anatomical neuropathic findings in schizophrenia?
decreases in neuron size, number of connections (dendrites and synapses), fewer connections between thalamus and cortex, and changes to cell skeleton
Which markers indicate decreases in synapses in schizophrenia?
synapsin, gap43, connexins
What are the 3 types of changes that occur in the brain?
Neurochemical, anatomical, and changes in trophic signalling or developmental pathways
What are the 3 general risk groups for schizophrenia?
genetic/epigenetic; perinatal (hypoxia during birth); and prenatal (pyrexia and starvation)
Schizophrenia is characterized by
excess of dopamine leading to psychotic features such as delusions and hallucinations
What neurochemical abnormalities are associated with schizophrenia?
excess dopamine; glutamatergic; GABAergic (ubiquitination where cells get ri of damaged proteins)
What signalling and developmental pathways have been implicated in schizophrenia?
neuregulin (NRG1), AKT1, Wnt/GSK
What is the importance of the Wnt pathway?
it decideds the fate of a cell - whether it becomes a neuron or not by regulating the cytoskeleton via glycogen synthase kinase 3 beta (GSK3b); expression of many of the components of the pathway are altered in schizophrenia and AD
What is the role of glial cells?
Regulation of synaptic activity
What affect on glial cells is found in the anterior cingulate (mood and affect) of bipolar disorder, schizophrenia, and major depression?
decreased glial cell density in deeper layers of cortex and decreased neuronal size
What affect on glial cells is found in the dorsolateral prefrontal cortex (mood and affect) of bipolar disorder, schizophrenia, and major depression?
decreased glial cell density and neuron volume in all 3 disorders
What is observed of glial cells in schizophrenia?
decreased density of cells and reduced neuron volume in deep cortical layers
What is the significance of elevated calprotectin in schizophrenic brains?
expressed by microglia, therefore a marker of inflammatory process (upregulation of the genes A8 and A9 for this protein are also upregulated)
What is the significance of microglia in OCD?
Hoxb8 gene is expressed only in microglia; Hoxb8-KO mice express OCD behaviour
How is autism linked to cortical growth?
Often an overgrowth in the frontal cortex that resolves by 7-8
How are microglia implicated in autism?
microglia in autistic DLPFC are enlarged and amoeboid - they look as if activated by inflammation but there are no associated inflammatory cytokines
What is observed of microglia in autism with respect to white and grey matter?
increased density in both grey (sig) and white matter; increased somal volume in grey matter (moreso in age <6) and moreso in white matter
What is a SNP?
When a single nucleotide differs within a population or individual
How are SNPs implicated in autism?
Parents pass on risk or protective SNPs (more protective = better); especially related to GRM5 receptor which dampens microglial activation and is decreased in autism
