Neuro Final

Name the three neurotrophic factors and their purpose

NGF (nerve GF), BDNF (brain-derived neurotrophic factor), GDNF (glial-derived neurotrophic factor)

NFs support synaptic survival and healing, and bind to receptors

What is the purpose of cell adhesion molecules?

Matures and stabilizes new synaptic sites

Ex: neurexins, neuroligins, ephrin, cadherins

Name some of the symptoms of lead on children

Motor coordination deficits, hearing deficits, ADHD, anti-social behavior

Name some of the symptoms of lead exposure on adults

Hypertension, neuropathy, irritabili

What forms the blood-brain barrier?

Endothelial cells lining the cerebral microvasculature

How does lead affect the BBB?

Lead damages astrocytes to increase BBB permeability, allowing toxicants in

Define caspases

Cystein proteases involved in apoptosis, require proteolytic processing

Caspase-3: cleaves intracellular substrate (chromatin, DNA, nuclear envelope)

Lead increases expression of caspase-

List the three types of oxidative stress and their effects

Protein oxidation: disrupts cellular function

Lipid peroxidation: disrupts membrane

DNA/RNA oxidation: mutation

What causes lead’s neurotoxic effects?

Lead has higher affinity than Zn and Ca++, and disrupts ATP synthesis and NMDA-receptor biology

Define dendritic spines and list the three shapes

Consists of head and neck, protrudes from dendrites

Mushroom, thin, stubby

Describe the purpose of mushroom dendritic spines

Receive input from large axonal terminals, ‘memory’ spines, strong synaptic transmissio

How can lead affect memory?

Lead increases aB plaque production (Alzheimer’s)

Describe the two processes of alcohol metabolization

Ethanol →(ADH) Acetaldehyde→ (ALDH)Acetate

Describe the cytotoxic effects of alcohol

Reduced NSC proliferation

Neural tube defects

Neural crest cell depth

Abnormal glial development

Reduced synaptic vesicles + cleft width

How does alcohol affect dopamine?

Alcohol reduces the expression of dopamine receptors

List some of the effects of intrauterine FAS

Autism, SIDs, Trout syndrome, pre-ecclampsia, inhibition of hippocampal development

What is the purpose of mitochondrial DNA?

How does alcohol affect mitochondrial DNA?

mDNA protects against oxidative damage

Alcohol disrupts ATP production, inhibits the ETC, causes a Ca++ overload, and disrupts the integrity of mDNA

What are NMDA/NMDARs?

Glutamate and Ca++ ion channel, important in learning, memory, and synaptogenesis, excitatory

Alcohol impairs functioning

What are AMPARs?

Glutamate and Na+ receptors, excitatory

How does alcohol affect GABA?

Alcohol upregulates GABA in the cerebral cortex

What is the leading known teratogen?

Alcohol

Name the three types of FAS

1. Growth deficiency

2. Cranio-facial abnormalities

3. CNS dysfunction

Explain the five types of FASD (fetal alcohol spectrum disorder)

1. w/ confirmed prenatal alcohol exposure

2. w/o 

3. Parietal FAS (milder)

4. ARND (alcohol-related neurodev. disorder)

5. ARBD (alcohol-related birth defects)

Define the difference between a cleft lip and a cleft palate

cleft lip: separations in the upper lip

cleft palate: separations in the upper palate

Define FAE

Fetal alcohol effect, milder than FAS

FAS always includes?

Brain damage

Describe the symptoms of FAS

Flat midface

Flat nasal bridge

Small eye openings

Hypoplastic philtrum

Microcephaly/microencephaly

frontal lobe defects

What are the three diagnostic criteria that must be met for FAS?

1. Pre/postnatal growth retardation

2. Developmental delays

3. 2/4 FAS facial features

Describe the function of the corpus callosum and how it is affected by alcohol exposure.

Fx: Connects two cerebral hemispheres

Alcohol causes absence of primordial tissue through:

1. reduced astrocytes

2. microglial apoptosis

3. reduced oligodendrocytes (white matter)

Describe the symptoms of agenesis of the corpus callosum

Impaired social skills

Lack of introspection

Poor communication of emotions

Lack of executive function

What is the form of mercury that bioaccumulates?

Methylmercury

Name 3 sources of methylmercury:

Dental amalgams, natural degassing (volcanoes), industrial waste

Describe the events leading to Minimata Disease:

Dumping of mercury in Minimata Bay, neurological problems/birds ‘dropping’, discovered by Dr. Hosokawa

Describe the events of mercury in Iraq, and list the three differences between this event and Minimata Bay

Iraq was a fungicide exposure

Differences: Shorter exposure time, identified earlier, new measurement techniques

Sx: boys more affected, ataxia, hypotonia

What do NSCs differentiate into and list the biggest effects of mercury in the body

Differentiate: Neurons, oligodendrocytes, astrocytes

Mercury induces apoptosis, increases ROS, impairs mitochondria, and alters Ca++ balance

How does mercury induce apoptosis?

Methylmercury increases the expression of Caspase C, which decreases cyclin E and stops the S phase of the cell cycle

Describe Notch signaling:

Notch stops NSC differentiation

Increased expression by mercury

Binds to transmembrane ligands, (NICD) moves to the nucleus, and initiates the gene that stops NSC differentiation

T/F: All forms of mercury are toxic

True

T/F Mercury affects genders differently

True, methylmercury has greater efects on males than females

Describe the recent trends in autism diagnoses

10x in 40 years

more in boys

Describe symptoms and effects of ASD

Symptoms

• Loss of babbling/sound communication

• No social orientation

Effects

• Increased brain volume/CSF

• mDNA mutations

• Increased ROS & synapses

Define autistic disorder

Repetitive behaviors, lack of speech and nonverbal communication

Define Asperger’s disorder

Developmental

Define CDD

Childhood disintegrative disorder, lack of non/verbal communication, backslide in developmental milestones

Rett’s disorder

In girls, affects speech, walking & coordination

Describe the MMR vaccine myth

• Came from a study of 12 children

• Thimerosal (preservative) can cause autism, removed from all vaxs in 2001, no correlation with autism rates

Describe three genetics disorders that include autism as a component

Fragile X: in males, expansion of trinucleotide CGG

Phenylketonuria: phenylalanine build-up

Tuberous sclerosis: affects communication, aggression

How can autism affect Shh and DNA packaging?

stops dna methylation

increases serum Shh and ROS

increased synapses (increased mTOR protein)

How does autism affect the main neurotransmitters?

decreases GABA

dysfunctional NMDAr (glutamate)

impaired serotonin and Ach

increases catecholamines in blood, urine, CSF

Describe the environmental components of autism

exposure to methylmercury in fish, corn syrup, atmosphere, thimerosal

glyphosate in herbicides may affect glutathione (GSH) which increases ROS