Intro Lecture 1 Notes
How does a biologist approach disease?
Gene->protein->complex->organelle->cell->tissue->organ->system
Anatomical/Physiological/Biochemical
e.g. Sickle Cell Anemia:
base change->valine 6 for glutamate 6 in beta globin chain-> deoxy form insoluble->polymerizes>distorts RBCs->microinfacts, bone pain, spleen and kidney damage
Understanding does not always lead to treatment, but often it does:
e.g. insulin for diabetes
How do biologists communicate results: papers
Title, intro, methods, results (figs), discussion
How does a clinician approach disease? Patient-based (case-based)
H&P standard format
Chief Complaint (CC)
History of Present Illness (HPI)
Past Medical History (PMH)
Review of Systems (ROS)
Family History (FHx)
Social and Environmental History (SocHx/EnvHx)
Medications and Allergies
Physical Exam
Laboratory Data
Assessment and Plan
Diagnosis:
1. Localization
2. Differential Diagnosis
Categories of Neurological Disease:
Trauma/Mechanical: e.g. subdural hematoma, herniated disk
Vascular: e.g. infarct, migraine
Epileptic
CSF Circulation: e.g. hydrocephalus
Toxic/Metabolic: drugs, electrolytes, endocrine, nutrition, organ failure
Infections: bacterial meningitis, AIDS
Inflamatory/demylenating: e.g. MS
Neoplastic: brain cancer
Degenerative: Alzheimers, Parkinson’s, Huntington’s
Developmental: inborn error of metabolism-Tay-Sachs, MR, autism etc.
Referred (e.g. left arm pain due to cardiac ischemia)
Psych
Other non neuro
Why is Neurobiology of Disease especially challenging?
Complexity of pathophysiology e.g. Huntington’s Disease: 1983 genetics (Wexler), 1993 gene:
Huntingtin, trinucleotide repeats (CAG -> polyglutamine) ->->-> degeneration of medium spiny cell in
striatum->->-> Chorea, psychosis, eventual death but how?
Much worse for polygenic diseases where diagnosis is clear (e.g. schizophrenia, autism)
Still worse for some disease where diagnosis is unclear: schizoaffective disorder:
Why is this an exciting time in the Neurobiology of Disease?
1. Genetics: human genome, transgenic animals, homologous genes in simple organisms,
mammals
2. Genomics/Proteomics/Interactomics
3. Cellular Biophysics in mammals
4. Imaging: cellular/subcellular with 2-photon, cognitive w/ fMRI etc.
5. Computational/infomatic: neural modeling, bioinformatics, neuroinformatics