Topic 8.3 - Mood and Neurodegenerative Disorders Flashcards
What are hallucinations?
Sensory stimuli that does not exist
What are delusions?
Incorrect analysis of information, despite evidence to the contrary
What are amine projections? What are their roles?
Ascending projections that release biogenic amine NTs to wide regions of the cortex.
–> Stabilize neuronal responses
What are biogenic amine NTs?
Serotonin, dopamine, NE.
What causes depression?
Insufficient release of biogenic amine NTs
–> Disturbs sleep, causes lack of energy and interest in life.
How can depression be treated pharmaceutically?
Through NE blockers or SSRIs
What are the two kinds of depression?
Unipolar and Bipolar
What is unipolar depression?
Endogenous and can be diagnosed based on biological or personal characteristics.
What is bipolar depression?
Characterized by alternating periods of depression and mania.
Depression is on one end of the biogenic amine spectrum. Which disorder exists on the opposite end of the same spectrum?
Schizophrenia
What causes schizophrenia?
Excess release of biogenic amines
–> Leads to delusions and/or hallucinations
How can schizophrenia be treated pharmaceutically?
With neuroleptic drugs that block dopamine or serotonin receptors.
Which disorder is characterized by disorganized thought processes, inadequate language skills, and false beliefs or ideas?
Schizophrenia
What are some risk factors for schizophrenia?
–> Genetic predisposition
–> Brain damage in fetus that leads to excessive dopamine secretion
–> Abnormal cells in hippocampus
–> Decreased blood flow to frontal lobes
What is the difference between an emotion and a mood?
An emotion of a brief expressive reaction to an event
A mood lasts a prolonged period of time and is not associated or attached to a particular event.
The hippocampus, amygdala, and hypothalamus are all part of which system?
The limbic system
Where is the hippocampus located? What is its role?
Located in the temporal lobes
–> Important for memory formation, spatial memory, and navigation
What is the role of the amygala?
To control and regulate emotions and emotional responses
–> Communicates with hippocampus to form emotional memories
What causes Alzheimer’s Disease? Which two phyiological changes are observed in individuals that have it?
Progressive cortical atrophy
–> Neurofibrillary tangles and plaques
–> Deficits of cholinergic level by loss of ACh neurons
How is Alzheimer’s Diagnosed?
No definitive diagnostic tests available
–> Diagnosed through survey tests and careful examinations of the medical and psychological history
What are Amyloid Plaques?
Aggregates of misfolded proteins that are formed in neurons.
–> Interferes with normal function and communications between neurons
What are neurofibrillary tangles?
Abnormal accumulation of Tau protein
–> Interferes with normal function and communications between neurons
What disease is first recognized by behavioral changes including irritability, hostility, mood swings, and gradual loss of memory, and eventually leads to a progressive loss of cognitive function, memory, and language? How long can this disease last?
Alzheimer’s
–> Can last over 10-20 years
What can be used to pharmaceutically treat Alzheimer’s disease?
Cholinesterase inhibitors
–> Prevent degradation of synaptically released ACh
–> Treats symptoms, but cannot reduce the progression of disease
What is the most common movement neurodegenerative disorder?
Parkinson’s
What is Parkinson’s characterized by?
–> Rigidity
–> Resting tremor
–> Bradykinesia
–> Postural instability
–> Dysphasia (swallowing or chewing issues)
–> Loss of facial function (Blinking, expressions)
What is the role of the D1 motor pathway that runs between the thalamus and cortex?
D1, aka the Direct Pathway
- Cortex excites striatum
- Striatum inhibits globus pallidus internal from inhibiting thalamus (D1)
- Thalamus excited cortex and activates motor programs
What is the role of the D2 motor pathway that runs between the thalamus and cortex?
D2, aka the Indirect Pathway
- Cortex excites striatum
- Striatum send inhibitory signals the globus pallidus external
- Globus pallidus external sends less signal to sub-thalamic nucleus
- Now less stimulates sub-thalamic nucleus becomes excited and send more excitatory signal to globus pallidus internal
- Excited GPI sends inhibitory signal to thalamus, which inhibits motor programs.
Incidence of Parkinson’s occurs in what percentage of individuals over 50?
1-2%
What area of the brain initiates a movement?
The basal ganglia
Which area of the brain sends input to the striatum and cortex to decide whether to activate the D1 or D2 pathway?
Substantia nigra
Parkinson’s Disease involves a loss of neurons in which structure?
Loss of neurons in substantia nigra that provides dopamine to striatum
What are Lewy bodies and Lewy neurites? They are a hallmark of which disease?
Hallmark of Parkinson’s Disease
–> Proteinaceous intracytoplasmic inclusions
What are some genetic factors that contribute to the development of Parkinson’s Disease?
–> LRRK2, GBA1, and SNCA risk alleles
–> SNCA duplication, triplication, or point mutation
–> Recessive gene mutation
What are some environmental risk factors for developing Parkinson’s Disease?
–> Farm life exposure
–> Chronic pesticide exposure
–> Recurrent head injuries
–> Neuroleptic drug exposure
–> H5N1 exposure
–> Manganese exposure
–> Single neurotoxin exposure
Parkinson’s Disease has a “complex etiology.” What does this mean?
Likely caused by a mix of genetic and environmental factors
–> Most likely a multi-hit phenomenon
How can Parkinson’s be treated?
–> Dopamine replacement therapy
–> Monoamine oxidate B inhibitor
–> Anticholinergic drugs
–> Physical and occupational therapy
What procedure can be used to reduce symptoms of Parkinson’s?
Deep Brain Stimulation
What disease is characterized by progressive degeneration of both upper and lower motor neurons?How long does this disease last?
Amyotrophic Lateral Sclerosis (ALS)
–> Disease lasts 2-5 years
Loss of upper motor neurons is associated with what?
Spastic paralysis and hyperreflexia
Loss of lower motor neurons is associated with what?
Flaccid paralysis and decreased tone and reflexes
What causes ALS?
There is no identified cause
–> Potential genes have been linked to disease
–> No indication of inflammation around nerves, or cognitive impairment
How does ALS progress?
Progressive muscle weakness and loss of fine motor coordination
–> Death occurs due to respiratory failure
What kinds of proteins are likely involved in the development of ALS?
Those involved in:
–> Proteostasis
–> Vesicle traffic
–> RNA metabolism
–> Oxidative stress
–> Mitochondrial dysfunction
What are some factors that make treating Parkinson’s difficult?
–> Complex etiology
–> Poor animal modelling
–> Because those with the disease live for decades, treatment must be incredibly safe
–> No biomarkers identified (progression is happening though)
What makes treating ALS so difficult?
–> No harmonized etiology
–> Highly stratified population
–> Short disease course leaves limited time for intervention
–> Poor biomarkers
Are the majority of ALS cases related to genetic etiology?
No, only a fraction of them are genetic
Which neurodegenerative disease is characterized by involuntary movements? What comorbidities does it often present with?
Huntington’s Disease
–> Presents with anger, OCD, and depression
–> Intellectual impairments may also present
–> Behavioural disturbances become more pronounces as dementia progresses
Huntington’s is a genetic disorder. What kind of gene causes it?
Dominantly inherited monogenic disorder.
Which disease is characterized by expansion of CAG tract and expansion of the PolyQ protein it codes for?
Huntington’s Disease
In what ways are Huntington’s and Parkinson’s similar? How are they different?
Similar int that they both involve issues with striatum and inhibition of its pathways.
However, where Parkinson’s involves issues signaling to both D1 and D2 pathways, Huntington’s involved issues signaling to the D2 pathway that inhibits excess movement.
How are ACh and GABA levels in the brain altered in someone with Huntington’s disease?
–> ACh reduced
–> GABA in basal nuclei is depleted
What is the current treatment for Huntington’s disease?
Currently no therapy to slow progression, and drugs target symptoms only.
What disease is characterized by progressive demyelination of neurons in the brain, spinal cord, and of cranial nerves?
Multiple Sclerosis
–> May affect motor, sensory, or autonomic fibers.
–> Occurs in diffuse patches in nervous system
Describe the process of MS.
Early lesions
–> Inflammatory response and loss of myelin in white matter
–> Formation of plaques (Areas of inflammation and demyelination)
Later
–> Function can reoccur for a short period of time, but neural degeneration will persist and permanent damage will occur
–> Each reoccurrence causes additional areas of CNS to be affected.
When is typical onset of MS?
20-40 years
What causes MS?
Unknown cause
–> Hypothesized to be autoimmune in origin
What are the initial symptoms of MS? How does it progress?
Initial symptoms include blurred vision, weakness in legs, dysarthria, areas of numbness, burning, and tingling
Progressive weakness and paralysis of upper limbs, and loss of coordination.
