MCB 135K: Discussion

March 2, 2005

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)

Topics

• Aging of the Nervous System:– Structural Changes– Biochemical Changes– Neuroimaging Studies and Normal Aging

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 informationCognition

Affect and moodFunctions of whole body systems

Aging of the Nervous System

• Structural Changes1. Changes in Brain

Weight

2. Neurons vs. Glial Cells

3. Denudation

4. Neuropathological Markers

• Biochemical Changes

1. Neurotransmitters2. CNS Synapses3. Neurotransmitter

Imbalance and Brain Disorders

• Brain Plasticity1. CNS Regenerative

Potential

Changes in Brain Weight

S tructural brain changes with agingchanges in brain volume

young old

FRONTAL

OTHER BRAIN REGIONS

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

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

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

NeurotransmittersTABLE 7-2 Neurotransmitters and Modulators in the Nervous System

Amines Amino Acids Peptides Others Acetylcholine Glutamate Enkephalin Nitric OxideCatecholamines Aspartate Cholecystokinin Carbon MonoxideNorepinephrine Glycine Substance P ZincEpinephrine GABA VIP* SynapsinsDopamine Taurine Somatostatin Cell Adhesion MoleculesSerotonin* Histamine TRH* Neurotropins

Others *Serotonin, 5-hydroxytryptamine, or 5-HTGABA or gamma-amino butyric acidVIP or vasoactive intestinal polypeptideTRH or thyrotropin-stimulating hormone

Synapses

• Cholinergic

• Adrenergic

• Serotonergic

• Gabanergic

Brain Disorders

• Parkinson’s Disease1. Pathologies

2. Symptoms

3. Treatment Strategies

• Alzheimer’s Disease1. Symptoms and Signs

2. Disease Progression

3. Pathophysiology

4. Treatment / Management

Parkinson’s Disease

• Loss of neuromelanin containing neurons in brain stem and presence of Lewy bodies in degenerating dopaminergic cells

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

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

Alzheimer’s Disease Progresses Alzheimer’s Disease Progresses Through Distinct StagesThrough Distinct Stages

Mild Moderate Severe

Memory lossLanguage

problemsMood swingsPersonality

changesDiminished

judgment

Behavioral, personalitychanges

Unable to learn/recallnew info

Long-term memory affectedWandering, agitation,

aggression, confusionRequire assistance w/ADL

Gait, incontinence,motor disturbances

BedriddenUnable to perform ADLPlacement in

long-term careneeded

Dementia/Alzheimer’s

Stage

Symptoms

TREATMENT & MANAGEMENT

• Primary goals: to enhance quality of life & maximize functional performance by improving

cognition, mood, and behavior

• Nonpharmacologic

• Pharmacologic

• Specific symptom management

• Resources

Imaging of the Brain

• Types of Neuroimaging

• Neuronal Recruitment and Reaction Time

STRUCTURAL FUNCTIONAL

Magnetic Resonance ImagingPositron Emission Tomography

Memory Load2 6 2 6

500

750

1000

1250

1500

Young Old

React

ion

Tim

e (

mse

c)

Summary

• Age-related decline in selective cognitive processes

• Functional MRI is a powerful method with excellent spatialand temporal resolution to study the physiological basis ofcognitive decline in normal aging

• Evidence for selective prefrontal cortical dysfunction(I.e. under-recruitment) with normal aging

• Possible neural as well as behavioral compensation