Week 2 Flashcards
Zika and side effects
symptoms: similar to Dengue such as rash, pain, maculopapular rash and conjunctivits
- associated with reports of microcephaly and guillain-barre syndrome
Zika and microcephaly
what is it, consequences, causes
What is microcephaly?: Microcephaly is often an isolated condition (occur with no other major birth defects/ occur in combination with other birth defects). Microcephaly is defined as a head circumference measurement that is smaller than a certain value for babies of the same age and sex - usually less than 2 standard deviations (SDs) below the average.
Consequences
Seizures, developmental delay (speech, walking), intellectual disability, movement and balance, hearing, vision
Causes
Chromosomal abnormalities
* Decreased oxygen to the fetal brain (cerebral anoxia)
* Infections of the fetus during pregnancy Including toxoplasmosis, cytomegalovirus, German measles (rubella) and chickenpox (varicella)
* Exposure to drugs, alcohol or certain toxic chemicals in the womb
* Severe malnutrition
* Uncontrolled phenylketonuria (PKU) in mother
Microcephaly - diagnosis
- First Trimester Screening:
- weeks 11-13
- Maternal Blood screen which measures human chorionic gonadotropin and preganancy associated plasma protein
- Ultasound screen to look for extra fluid behind baby’s neck.
- 2. Diagnostic Test: only happens if a screening test is abnormal, or if mother has a high risk pregnancy (older women, previous pregnancy had birth defect, women with chronic illnessor women on medication)
Guillain Barre Syndrome
-possible auto immune disorder
- weakness and tingling
- may result paralysis
- **Acute inflammatory demyelinating polyradicularneuropathy
- Miller Fisher syndrome
- Acute motor axonal neuopathy and acute motor sensory axonal neuropathy
- ** often preceded by infectious illness such as flu
- effects of a genetic ablation of AXL regarding the ZIKA virus
- How does the ZIKV impact brain organoid vs. human neurosphere?
- Genetic ablation of AXL does not proetct neural progenitor cells and cerebral organoids from Zika virus
- Zika in neurosphere and brain organoid= growth reduction (reduced size). In neural stem cell zika= cell death= reduced size of neurosphere
Parkinson’s Disease
Risks
- 1-2% of people over 60-65
0.3% of general population - male to female ratio: 3:2
- age is greatest risk factor
- people with PD is supposed to rise
- Parkinsonism is defined by four cardinal motor features
- Non-motor features (5)
- pre-motor features (6)
- other causes of PD, incorporation of other diseases (4)
Parkinsonism is defined by 4 motor features:
1. Bradykinesia (movement slowness)
2. rest tremor
3. rigidity
4. postural and gait impairment
**Non-motor features **
neuropsychiatric (depression, anxiety), sleep disorder, sensory dysfunction, pain, fatigue
Pre-motor features: occur before motor symptoms:
Impaired olfaction, constipation (GI issues), depression (pre or non motor), daytime sleepiness, rapid eye movement sleep behaviour disorder, changes in speech maybe
Other Causes of Parkinson
Other neurodegenerative diseases: Demntia with Lewy bodies , multiple system atrophy, progressive supranuclear palsy,
Structural brain leisons: cerebrovascular disease (atherosclerosis)
Infectious/Post infectious: Post TBI
Drugs: Anti pyschotic meds
Basal Ganglia System
Group of nuclei located deep in the brain. Leisons in the basal ganglia= motor dysfunction
1. Striatum (Caudate, Putamen)
2. Globus Pallidus
3. Subthalamic nucleus
4. Susbtantia Nigra (dopamine production site)
5. Pedunculopontine nucleus
- List the two key pathological features of PD
- Dopamine in substatia nigra (major source of dopamine) and PD
- Neurodegeneration and Clinical SYmptoms
1) Loss of dopaminergic neurons within SN
(2) Lewy bodies presence (protein aggregates) in SN
2. Dopamine is required for normal functioning of BG. Major source of dopamine is from the neurons in SN pars compacta which has tyrosine hydroxylase that makes dopamine. In PD we lose TH producing neurons which are dopaminergic neurons in SNc and this results in motor and non motor symptoms of PD
3. neuronal death can occur before symptoms appear in neurodegenerative
diseases and PD leads to progressive DA neuron loss = loss of DA = failure of BG
Lewey Bodies
- aggregation of abnormally folded proteins
- common feature of neurdegenerative disease
- lewey bodies in (neuronal cell bodies) and Lewy neuites in (neuronal cell proccess) are characteristic protein aggregates in PD
3 Other pathological features of PD and their examples
- Loss of neurons in other brain regions
Locus cerulus (noradrenaline), nucleus basalis of meynert and pedunculopontine nucelus (acetylcholine), Raphe nuclues (serotonin) - Varied protein aggregates
Amyloid paques, and neurofibrillary tangles - neuroinflammation
Microglia activation and cytokine presence (ex: more of IL-6, IL-1 Beta) in parenchyma
Treating Parkinson’s Disease:
3 ways to do Dopamine Replacement Therapy
Limitations
- dopamine replacement using
- L-Dopa (precursor to dopamine)/ COMT inhibitor: COMT inhibits dopamine
- Dopamine agonsist (act like dopmine)
- Monoamine oxidase type B (MAO-B) inhibitors. MAO-B breaks down dopamine
- this improves bradykineasia and rigidity
Limitations - motor symptom improvement is inconsistant
- few non motor symtpoms improve
- dopaminergic treatment complcications involve: psychotic symtpoms (hallucinations), fluctutation of symtoms, and new involuntary movements
- Etiology means
- PD can be caused by
- mutations in (number) genes that are identified as causes of PD but
- Etiology means the cause of disease.
- PD can be caused by environmental factors, genetic factors, and
a mix of both genetics and environments - \Genetic causes of PD: 10% of PD patients have family members with PD\
- There are mutations in seven genes that are identified as causes of PD but
mutations in one of these gene is rare (3-5%)
5 molecular/cellular pathways involved in PD
- protein aggregation
- proetin handling
- protein degradation
- synaptic structure/function
- mitochondrial function (reduction)
**a-synuclein and PD **
* how SNCA gene mutations contribute to PD
* lewey bodies
* Can Lewy pathology account for all neuronal death why or why not
Missense mutations, duplication and triplications in SNCA are assocated with familial PD
aggregated a-synuclein is major componenet of lewy bodies. Lewy pathology cannot account for all neuronal death.
o Some people have Lewy bodies without neurodegeneration and PD.
o Neurodegeneration can occur without Lewy bodies (i.e. Parkin).
