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Animal Models Of Brain Disorder (Short) Notes

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Animal models of brain disorder Why do we need animal models of brain disorder?
What brain disorders can we model?
How do we test the validity of a model?
How do we construct a model?
How do we make genetic models?
Mouse vs. man Charles Darwin, The Descent of Man - "...the difference in mind between man and the higher animals, great as it is, certainly is one of degree and not of kind..." Why do we need animal models?

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High cost and time investment of clinical studies and trials Technical challenge of measuring neural function in patients Need to understand better the neurobiological basis of symptoms Investigate the role of genes and signaling pathways in disease pathophysiology Investigate the role of gene/environment interactions in disease pathophysiology Make better and more effective treatments

Examples of brain disorders that we think that we can model PSYCHIATRIC DISORDERS: Depression Anxiety Schizophrenia Compulsive drug use NEURODEGENERATIVE DISORDERS: Alzheimer's Parkinson's Huntington's OTHER NEUROLOGICAL DISORDERS: Epilepsy Cerebral ischemia (stroke) Testing the validity of a model

1. construct validity - How good is the theoretical rationale? (gene mutation, neuronal lesion, developmental origin)

2. face validity - how good are the similarities with the human condition?
(behavioural symptoms, neuropathology)

3. predictive validity - how accurate are predictions made from the model (effects of treatments, disease progression) Constructing an animal model

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Pharmacological manipulation o Neuronal lesion o Transmitter modulation Environmental manipulation o Behavioural conditioning o Behavioural stressors o Adverse early life events Genetic manipulation o Gene KO o Gene knock in o Selective breeding o Chemical mutagenesis

Some animal models of depression

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Environmental stress o Chronic mild stress o Social defeat Maternal separation o Rodents o Primates Selective breeding o "Rouen depressed mice" olfactory bulbectomy tryptophan-free diet stimulant-induced hyperactivity (mania)

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