2/26/15 – lecture 13 – - Goal: to learn how neurodegenerative diseases affect the nervous system- Neurodegenerative Diseases: diseases that result in the progressive destruction of neuronso They are progressive and get worse and worse over timeo They don’t tend to manifest until late adulthoodo Neurons typically die by apoptosis (cell suicide) 3 examples of neurodegenerative diseases (brain regions very important, symptoms, and proteins and genes involved) Least Common to Most Common- Huntington’s Disease: degeneration and death of neurons predominately in the basal ganglia (motor areas) and cortexeso Inherited or genetic disorder caused by deficit in the huntingtin gene (1 in10,000 people affected)o Symptoms Chorea: random jerky movements (motor cortex)- Specific to huntington’s Dementia: progressively impaired cognitive function (cortex where memory is kept)- Similar in all 3 diseases Psychiatric symptoms (secondary): anxiety, depression, blunted affect, egocentrism, aggression, and compulsive behavior- Egocentrism is unique to huntingtonso Brain Changes in Huntington’s Disease Generalized and progressive brain atrophy, particularly in the cerebral cortex (memory) and basal ganglia (movement)- Basal ganglia: producing voluntary movement, and inhibiting voluntary movemento Neuropathological changes in Huntington’s Disease Huntington gene, misfolding, inclusion bodies, calcium blocking  Huntington protein mis-folds and accumulates in aggregates called inclusion bodies - Inclusion bodies block the peptide neurotransmitter transport to axon- Inclusion bodies also disrupt gene expression, calcium signaling, and mitochondrial functioning Can lead to apoptotic cell death because hunington inhibits apoptosis (meh)- Alzheimer’s Disease: degeneration and death of neurons predominantly in the limbic system and cerebral cortex, cause is unknown but genetics, infection, oxidative stress are thought to be possible triggers (10% of people over 65) – genes influence it, but environment also interacts with the genes to cause the diseaseo Symptoms of Alzheimer’s Disease Dementia: progressively impaired memory and cognition- Apart of all of the diseases but most noticed with Alzheimer’s Psychiatric Symptoms: depression, irritability, aggressiono Brain changes in Alzheimer’s Death of cholinergic neurons in the basal forebrain – attention Death of neurons in the medial and temporal cortex and hippocampus – formation of memories Death of neurons in the prefrontal and other parts of the cortex and limbic system – long term memory and emotional regulation- Control over self and higher level thinking and emotional controlo Neuropathological Changes in Alzheimer’s Abnormal folding of amyloid protein Misfolded amyloid protein accumulates with many other proteinsincluding a protein called tau in neurofibrillary tangles- Disrupt the neuronal functions- Clump together and kill off the cells in the brain through apoptotic cell death- When the neurons die they leave behind amyloid filled plaqueso Continues on and on as the neurons die off- Parkinson’s Disease: degeneration and death of dopaminergic (dopamine) neurons within the substantia nigra, can be causes by genetics, infections, neurotoxins, and trauma (1 in every 200 people – most common)o Muhamad Ali – environmental case, Michael J. Fox – genetic caseo LDopa- drug that increases dopamine levels in the brain to help Parkinson’s But people took too much and the body stopped reacting righto Symptoms of Parkinson’s Motor symptoms: pronounces tremor of head and extremities, rigidity and difficulty producing voluntary movements Psychiatric Symptoms: dementia, depression, anxiety, etc.o Brain Changes in Parkinson’s Abnormally low levels of dopamine caused by degeneration and death of neurons in the substantia nigra in the mid brain- Substantia nigra is involved in the initiation of voluntary movement (ON THE TEST)o Neuropathological Changed in Parkinson’s Cause of neuronal degeneration and death is not known Lewy bodies, circular structures containing the protein alpha synclein, are found in the neurons and may represent abnormal protein accumulations that disrupt neuron function and lead to death- Iron or aluminum accumulation in the substantia nigra is often observed, and often associated with the Lewy Bodies- Defects in protein degradation and mitochondrial function in dopaminergic neurons from Parkinson’s patients are also observed Cognitive Reserve and Neurodegenerative Disorders- Cognitive Reserve: the ability of the brain to cope with damage to or loss of neurons in response to neurodegenerative conditions or other insultso Comes in part from how strong our brain is when the degeneration startso Comes in part from how able our brain is to increase the strength of remaining synaptic connections, form new synaptic connections, and to form new neurons (in the hippocampus) Greater cognitive reserve allows some individuals to function more normally than others even with the same disease Cognitive reserve is influenced by genetics but also by environment – education, exercise, nutrition, occupation- Mainly helpful with Alzheimer’s, less helpful with