Genetically, what is potential cause for autism?
CNVs are one cause (16p11.2 deletion/duplication syndrome, which includes features of ASD), nonsense/indel/splice sites/missense mutations are another.
Both common and rare variants have been associated with the diseae. Many WES studies looking for de novo mutations, also some GWAS to look for common variants with ASD.
What are the pontential causes for autism?
Likely due to both genetic and environmental factors. Males more likely to have ASD than females: individual has increased risk for ASD if family member has ASD; older parent age linked to ASD.
Neurodevelopmental disorder; difficulty with social interactions/communication and restrictive/repetitive behavior/interests/activities.
What makes the maxilla and mandible?
First branchial arch is what makes the maxilla and mandible (pharyngeal arch - branchial arch).
Central nervous system disorder that mainly affects the motor system
The slowness in initiating movements, with progressive reduction in speed and range of repetitive actions such as involuntary finger-tapping in combination with other physical signs.
What roles do neurons play?
Neurons can play very different roles: excitatory or inhibitory - they do this action on the downstream neuron.
What are the functional pathways commonly mutated in ASD?
Several functional pathways are commonly mutated in ASD:
- a) chromatin remodeling (e.g., CHD2 and 8, chromatin remodeling helicases)
- b) protein synthesis and degradation/cell proliferation (e.g., mTOR pathway and ubiquitin-proteasome system genes),
- c) synaptic functions (e.g., CACNA1D, a calcium channel Gene, and SYNGAP1 and NRXN1, required for proper synapse function).
What are the how many prominences/processes are associated with orofacial clefting phenotypes?
Four key prominences/processes associated with orofacial clefting phenotypes:
- Two medial nasal prominences (formed from frontonasal prominence; these fuse to form an intermaxillary segment)
- Two maxillary processes
This produces the primary palate.
What are the three brain regions that work together to control movement?
- Substantia Nigra
All work together to control movement
What happens to alpha-synuclein in PD patients?
Alpha-synuclein in particular accumulates in brains of PD patients due to the inability to properly degrade it in the lysosomes (in "Lewy Bodies").
What do the direct pathway and indirect pathway control?
Making movements is controlled by direct pathway, not making movements is controlled by indirect pathway.
What is the essential cause of Parkinson's disease?
Death of cells in substantia nigra portion of brain (located in midbrain and plays an important role in movement). These neurons produce the neurotransmitter dopamine, and thus the disease is caused by reduced levels of dopamine.
What mental illnesses are group under autism spectrum disorder?
- Asperger's Syndrome
- Childhood Disintegrative Disorder
Describe the knee reflex...
In the knee reflex, the sensory neuron acts as the excitatory neuron causing quads to contract, but also excites the interneuron, which is an inhibitory neuron causing the hamstring muscle to relax.
What are the causes of Parkinson's disease?
Likely due to both genetic and environmental factors (e.g., exposure to pesticides or head trauma; reduced risk for caffeinated coffee/tea drinkers!).
Describe the direct pathway...
Thalamus wants to make muscles move, but it is inhibited. Aim of direct pathway is to TAKE AWAY INHIBITION of thalamus.
Thalamus to motor cortex to muscles.
First, motor cortex signals to striatum, which inhibits globus pallidus internal; since GPI normally inhibits thalamus, this results in signaling to motor cortex to allow muscles to move.
Substantia nigra and subthalamic nucleus fine-tunes movement. SN sends dopaminergic neurons to striatum to synapse on inhibitory neurons to GPI, thus further exciting inhibitory neurons (further inhibiting GPI) which results in greater activation of the thalamus. STN excites SN, SN inhibits STN.
What can be said about the rapidity of the development of symptoms in Parkinson's disease?
Symptoms usually come on slowly and progress over time.
What are the genes implicated in PD?
On the top of the list is SNCA (alpha-synuclein), then are:
- PARK 7
Severeal of these genes are involved in function of lysosomes, organelles in the cell that digest cellualr waste products.
How is Parkinson's Disease treated?
Treatment includes administration of Levodopa (L-Dopa), which is the precursor to dopamine capable of crossing the blood-brain barrier.
What is clefting a result of?
Cleft lip due to failure of maxillary process to fuse with intermaxillary segment/medial nasal prominence.
Cleft palate due to failure to fuse palatal shelves (palatine processes; forms the secondary plate).
What can be said about the knock down of gpc5 and gpc6?
Taking out gpc5 there was an effect; taking out gpc6 nothing occurred, normal development; but, taking out both exacerbates the condition; this means there is ome redudancy in which gpc6 aids in the process; however, main player is gcp5.
What are GABA and glutamate?
GABA is inhibitory neurotransmitter, glutamate is excitatory neurotransmitter.
What are the key signs of autism?
- Communication/Social: non-verbal cues, trouble expressing needs)
- Behavioral: restrictive Interests such as "Cars", repetitive behavior such as lining up toys.
- Responses to environmental stimuli: don't follow "stimulis line" for arousal for example (sporatic, instead of linear).
Describe the indirect pathway...
Exciting GPI (globus pallidus internal) through inhibition of GPE, resulting in increase in activity of STN which stimulates GPI, thus “tightening leash.” SN loosens leash a bit by allowing GPE to be turned up thus allowing GPI to be turned down.