Animal Models

Question 1

What premise is the use of animal models based on?

Answer 1

It is based on the premise that basic physiological, metabolic, and developmental pathways were conserved over the course of evolution. They allow causality

Question 2

What is the role of neuroimaging in animal models of Autism Spectrum Disorder (ASD)?

Answer 2

Neuroimaging in animal models of ASD is used to identify potential translational biomarkers.

Question 3

What type of neuroimaging technique is used to study brain anatomy?

Answer 3

Structural MRI (Magnetic Resonance Imaging) is used to study brain anatomy.

Question 4

What type of neuroimaging technique is used to study neural activity, brain circuitry, and connectivity?

Answer 4

Functional MRI (fMRI) is used to study neural activity, brain circuitry, and connectivity.

Question 5

What type of neuroimaging technique is used to study neurotransmitters and metabolites (Neurochemical component)?

Answer 5

Magnetic Resonance Spectroscopy (MRS) is used to study neurotransmitters and metabolites (concentration).

Question 6

Why is the mouse genome advantageous for research?

Answer 6

The mouse genome is easily manipulated to produce animals that copy human conditions, allowing for precise genetic studies.

Question 7

What is the benefit of identical genetic alteration in mice?

Answer 7

Identical genetic alteration in all mice reduces interindividual variability, making research results more consistent.

Question 8

What types of characterizations are possible with mouse models?

Answer 8

Both pre- and postnatal characterizations can be conducted on mouse models.

Question 9

What can be studied using mouse models in terms of genetics?

Answer 9

individual and combinatorial genetic effects & gene-environment interactions

Question 10

What types of analyses can be performed on mouse models?

Answer 10

Multiple imaging modalities and postmortem analyses

Question 11

What criteria should be considered when selecting animal models for research?

Answer 11

Face validity: The extent to which the animal phenotype resembles human symptoms.

Construct validity: The model has the same etiology and underlying mechanisms as the human disorder.

Predictive validity: The model reliably predicts treatment responses in human patients

Question 12

Are there identified biomarkers or a ASD-specific pharmacological treatments?

Answer 12

NO

Question 13

What is a limitation of rodent models of Autism Spectrum Disorder (ASD)?

Answer 13

Rodent models of ASD have various underlying etiologies and construct validity for only very limited ASD sub-populations.

Question 14

What is one model of autism in terms of neural activity?

Answer 14

One model of autism involves an increased ratio of excitation to inhibition in key neural systems.

Question 15

What have translational research studies using mouse models shown about GABA and glutamate in humans?

Answer 15

Translational research using mouse models has shown that imbalances in GABA (inhibitory neurotransmitter) and glutamate (excitatory neurotransmitter) are implicated in the neural mechanisms underlying autism in humans.

Question 16

What has neuroimaging studies implicated in the pathophysiology of repetitive behavior?

Answer 16

Neuroimaging studies have implicated corticostriatal circuitry in the pathophysiology of repetitive behavior.

Question 17

What is the BTBR mouse model used for in Autism Spectrum Disorder (ASD) research?

Answer 17

The BTBR mouse model is commonly used to study various aspects of Autism Spectrum Disorder (ASD), including social behavior deficits and repetitive behaviors.

Question 18

Which two drugs have been tried in clinics doe treatment of repetitive behaviours n children with ASD

Answer 18

Oxytocin (reduced grooming- hypothalamus)
N- actelycysteine (reduced digging -striatum)

Question 19

What technique is behind optogenetics?

Answer 19

Researchers can modulate the activity of targeted (genetically modified) neurons using light

Question 20

What genetic anomaly characterizes Williams syndrome?

Answer 20

Williams syndrome is caused by a spontaneous (hemizygous) deletion on chromosome 7 (7q11.23), which involves the deletion of 26 genes.

Question 21

What is FISH (fluorescent in situ hybridization) used for in testing for Williams syndrome?

Answer 21

FISH is the most common method of testing for Williams syndrome. It shows only one copy of the elastin gene, indicating the presence of the characteristic hemizygous deletion on chromosome 7.

Question 22

What is the significance of the elastin gene in Williams syndrome?

Answer 22

In Williams syndrome, the absence of the elastin protein, which is made only during the prenatal period, leads to vascular problems later in life. The missing elastin gene is used to identify the missing genes in Williams syndrome.

Question 23

What do GABAa agonists cause?

Answer 23

cognitive impairments

Question 24

What is the downside to non-selective GABAa inverse agonists?

Answer 24

proconvulsive and anxiogenetic effects

Question 25

Where are GABAa alpha5 receptors predominantly expressed?

Answer 25

hippocampus & cortex

Question 26

What can selective GABAa alpha5 inverse agonists achieve?

Answer 26

memory performance enhancement

Question 27

What effect did the administration of ALGERNON to pregnant dams have on Down syndrome (DS) mouse embryos and offspring?

Answer 27

rescued aberrant cortical formation in DS mouse embryos and prevented the development of abnormal behaviors in DS offspring.

Question 28

What is the most common cause of inherited intellectual diability and is second only to Down syndrome as the most common genetic cause of intellectual disability?

Answer 28

Fragile X syndrome

Question 29

How is Fragile X syndrome inherited, and how does it affect males and females differently?

Answer 29

Fragile X syndrome is an X-chromosome linked disorder. It tends to be milder in females compared to males, who typically exhibit more severe symptoms.

Question 30

Where is the mutation associated with Fragile X syndrome located?

Answer 30

at Xq27.3, specifically in the untranslated region of the FMR1 gene.

Question 31

What are the 3Rs principles in animal research?

Answer 31

1. Replacement (reducing the use of animals where possible)
2. Reduction (minimizing the number of animals used)
3. Refinement (enhancing animal welfare and reducing suffering during experiments).