1. MCB 135K: Discussion March 2, 2005

2. General Info Mid-Term I: –Avg 87 –Std. Deviation 10 –Re-grades by next Wednesday Include a cover sheet that addresses the question(s) you want us to look at and why you believe they need re-graded (included references as necessary)

3. Topics Aging of the Nervous System: –Structural Changes –Biochemical Changes –Neuroimaging Studies and Normal Aging

4. Major Function of the Nervous System The major function of the CNS is to communicate & to connect: –with other CNS cells –with peripheral tissues (outside CNS) –with the external environment (including physical and social environments) This regulates: Mobility Sensory information Cognition Affect and mood Functions of whole body systems

5. Aging of the Nervous System Structural Changes 1.Changes in Brain Weight 2.Neurons vs. Glial Cells 3.Denudation 4.Neuropathological Markers Biochemical Changes 1.Neurotransmitters 2.CNS Synapses 3.Neurotransmitter Imbalance and Brain Disorders Brain Plasticity 1.CNS Regenerative Potential

6. Changes in Brain Weight

7. Neurons vs. Glial Cells Neurons - Avg. 10,000 Connections –Cell Body –Axons –Dendrites –Synapses Glial Cells – 10-15 X the # of Neurons –Astrocytes –Oligodendrocytes –Microglial

8. Denudation Normal Aging –A, B, C –Due to small amounts of neuronal loss (?) –Increased dendritic growth Degenerative Disease –AD,E,F Senile Dementia of AD –A,D,G,E,F Pre-Senile Dementia of Familial Type AD –Progressive loss of dendritic spines –Eventual Cell Death

9. Neuropathologies Lipofuscin –By-product of cellular autophagia –Linear increase with normal aging –Function in disease unkown Lewy Bodies –Present in normal aging (60+) –Increased accumulation in Parkinson’s Disease Neurofibrillary Tangles –Tangled masses of fibrous elements –Present in normal aging in hippocampus –Accumulation in cortex is sign of Alzheimer’s Paired Helical Filaments –Role in Neurofibrillary tangle formation

10. Neurotransmitters

11. Synapses Cholinergic Adrenergic Serotonergic Gabanergic

12. Brain Disorders Parkinson’s Disease 1.Pathologies 2.Symptoms 3.Treatment Strategies Alzheimer’s Disease 1.Symptoms and Signs 2.Disease Progression 3.Pathophysiology 4.Treatment / Management

13. Parkinson’s Disease Loss of neuromelanin containing neurons in brain stem and presence of Lewy bodies in degenerating dopaminergic cells

15. Parkinson’s Disease Symptoms –Loss of motor function –Loss of balance –Speech and Gait abnormalities –Tremor –Rigidity Treatment Strategies –Pharmacological Ldopa –Neuroprotective –Surgical –Cell Therapies

16. Alzheimer’s Disease Risk Factors Apolipoprotein E4 on chromosome 19 Late-onset AD APOE*4 allele  risk &  onset age in dose-related fashion APOE*2 allele may have protective effect Pathophysiology –There are 3 consistent neuropathological hallmarks: Amyloid-rich senile plaques Neurofibrillary tangles Neuronal degeneration –These changes eventually lead to clinical symptoms, but they begin years before the onset of symptoms

19. TREATMENT & MANAGEMENT Primary goals: to enhance quality of life & maximize functional performance by improving cognition, mood, and behavior Nonpharmacologic Pharmacologic Specific symptom management Resources

20. Imaging of the Brain Types of Neuroimaging Neuronal Recruitment and Reaction Time

21. STRUCTURALFUNCTIONAL Magnetic Resonance ImagingPositron Emission Tomography

22. Memory Load 262 6 500 750 1000 1250 1500 Young Old Reaction Time (msec)

24. Summary Age-related decline in selective cognitive processes Functional MRI is a powerful method with excellent spatial and temporal resolution to study the physiological basis of cognitive decline in normal aging Evidence for selective prefrontal cortical dysfunction (I.e. under-recruitment) with normal aging Possible neural as well as behavioral compensation