Exam 1 Flashcards

Question

What are treatments for strokes? (Mechanical thrombectomy)

Answer 1

■ Angioplasty ■ Physical removal of the clot through endovascular surgery with a stent

Answer 2

NMDA blocker look at slide

Answer 3

Electrical signals travel down the axon as ion channels open and close Every cell has a voltage (difference in electrical charge) across its plasma membrane called a membrane potential ■ The resting potential is the membrane potential of a neuron not sending signals

Answer 4

Maintained predominantly by the potassium leak channel – Aided by sodium leak channel and Na+/K+ pump Gated ion channels are responsible for electrical signaling

Answer 5

The inside of the cell more negative – For example, K+ exiting the cell or Cl entering the cell Graded hyperpolarizations produced by two stimuli that increase membrane permeability to K+.

Answer 6

The inside of the cell becomes more positive ■ For example, Na+ channels open and Na+ diffuses into the cell Graded depolarizations produced by two stimuli that increase membrane permeability to Na+.

Answer 7

An action potential is an extreme depolarization of the neuron (c) Action potential triggered by a depolarization that reaches the threshold.

Answer 8

``` Resting state: Voltage gated Na+ and K+ channels are closed; resting potential is maintained by ungated channels (not shown). ```

Answer 9

``` Depolarization: A stimulus (ligand) opens some Na+ channels; if threshold is reached, an action potential is triggered. ```

Answer 10

``` More Na+ channels (voltage gated) open, K+ channels remain closed; interior of cell becomes more positive. Membrane polarity becomes the reverse of resting state. 3 ```

Answer 11

``` Repolarization: voltage-gated Na+ channels close and inactivate; voltage-gated K+ channels open, and K+ rushes out; interior of cell becomes more negative than outside. ```

Answer 12

The voltage-gated K+ channels close relatively slowly, causing a brief undershoot.

Answer 13

``` -Inactivated Na+ channels behind the zone of depolarization prevent the action potential from traveling backwards -During the refractory period after an action potential, a second action potential cannot be initiated because of the temporary inactivation of the Na+ channels ```

Answer 14

``` -Inactivated Na+ channels behind the zone of depolarization prevent the action potential from traveling backwards -During the refractory period after an action potential, a second action potential cannot be initiated because of the temporary inactivation of the Na+ channels ```

Answer 15

``` -Voltage-gated channels are restricted to nodes of Ranvier ■ Action potentials in myelinated axons jump between the nodes of Ranvier in a process called saltatory conduction ```

Answer 16

``` 1- Increased Ca2+ level through voltage-gated Ca2+ channels cause vesicles to release neurotransmitters by exocytosis ``` ``` 2- Neurotransmitters can act as ligands that affect ion channels on the posy-synaptic neuron ```

Answer 17

When a neurotransmitter makes a neuron less likely to fire, it is inhibiting its firing: Inhibitory post -synaptic potential (IPSP)– GABA ■ When a neurotransmitter makes a neuron more likely to fire, it causes an excitatory postsynaptic potential (EPSP)–Glutamate ■ The summation of excitation and inhibition determines whether or not it will transmit a nerve signal

Answer 18

A single EPSP is usually too small to trigger an | action potential in a postsynaptic neuron

Answer 19

Two ESPS, (time) summation, creates an action potential

Answer 20

Same charge: Adding enough positive charges from different neurons can be enough to trigger an action potential Opposing charges: Adding together opposing charges can prevent an action potential

Answer 21

■ Abnormal, highly synchronous electrical activity of a restricted brain region, or in some cases encompassing the whole brain ■ Having a seizure does not make a person epileptic Seizures can be detected using an EEG ■ Electroencephalograph (EEG)

Answer 22

``` Seizures ■ Focal (Partial) Seizures – focal seizure without cognitive impairment (simple) – focal seizure with cognitive impairment (complex) ``` ``` Generalized Seizures – Absence – Tonic-clonic – Atonic – Myoclonic ```

Answer 23

■ A seizure that lasts longer than 5 minutes, or having more than 1 seizure within a 5 minutes period, without returning to a normal level of consciousness between episodes ■ Medical emergency that can lead to death

Answer 24

Spontaneous, repeated unprovoked seizures ■ Genetic/idiopathic epilepsy – Channelopathies – Presents in early childhood and adolescence Symptomatic or acquired epilepsy – Well defined underlying cause Seizures are caused by excitation/inhibition imbalance

Answer 25

■ Group of neurons spontaneously develop synchronous firing – Excitation passed through gap junctions – Alterations in inhibitory signals from basket cells – Groups of neurons that are individually hyperexcitable ■ Increase in extracellular K+ – Abnormal interactions between groups of neurons ■ Ion channel mutations

Answer 26

■ Little research done on period of time before seizures begin when rewiring most likely occurs

Answer 27

Reuptake of Glutamate; Excess glutamate taken in by astrocytes at the synapse and converted to glutamine

Answer 28

■ Exome sequencing often reveals mutation in ion channels in individuals suffering from epilepsy – De novo – familial

Answer 29

``` Monozygotic twins- if one is affected, there is a 50-60% chance the other will be as well ■ Dizygotic Twins- 15% ■ Closely related relative have a 5X higher risk of developing epilepsy than the general population Epilepsy Tends to Have Autosomal Dominant Inheritance ```

Answer 30

Single gene mutation seems to explain the development of disease ■ SCN1A- encodes for the alpha subunit of the neuronal voltage gated channel responsible for the AP

Answer 31

``` ■ Missense mutations may or may not cause epilepsy ■ Truncations almost anywhere are causative ■ Different mutations cause different phenotypes SCN2A mutations are seen in familial epilepsy ```

Answer 32

``` Voltage gated K+ channel ■ Mutations tend to slow the repolarization of the cell ■ Associated with benign familiar neonatal seizures ```

Answer 33

Reduced GABA receptor mediated inhibition-> increased excitability of pyramidal neurons

Answer 34

■ Combination of small changes leads to a phenotype that may confer heightened susceptibility to seizure under certain conditions – Stress – Hypoxia – Development linked to a combination of genetic and environmental factors/triggers

Answer 35

``` Chemical induction through injection of glutamate receptor agonist ■ Focal seizures- often used to mimic frontal lobe seizures ```

Answer 36

``` Recurrent electrical stimulation ■ Ultimately seizures present without stimulation ■ Examine latent period- time before spontaneous seizure formation ```

Answer 37

■ EEG abnormalities mirror those seen in humans ■ Abnormal network connections in hippocampus and cortex can be observed ■ Manipulation of transmitter systems shown to cause seizures in mice – Increase Glutamate – Decreased GABA ■ Changes in ion channels- gene mutation research ■ Structural changes lead to epilepsy (lesion model) ■ Trauma, infection and vascular changes can be studied

Answer 38

``` ■ Excess glutamate taken in by astrocytes at the synapse and converted to glutamine ■ Mutation to transporter (EAAT2) linked to seizures ■ Mutation to Kir4.1 K+ channel – extracellular K+ not cleared – Enhances BDNF secretion (high concentrations linked to epilepsy) ```

Answer 39

■ Neurogenesis altered following seizures ■ Newborn cells are not incorporated properly into the circuitry ■ Leads to more seizures

Answer 40

``` Signaling protein associated with growth and proliferation ■ mTOR in the brain is regulated by pathways involved in glutamatergic, excitatory transmissions ■ Rapamycin – drug that can inhibit mTOR ```

Answer 41

Act to raise the threshold for neuronal network excitability ■ Over 20 drugs available that target different proteins ■ Augmenting GABA response Reduction in Na+ channel activity ■ Alter neurotransmitter release

Answer 42

■ “Freedom from seizures” for 2/3 of individuals ■ Does not always equate with normal EEG activity- just reduction in behavioral problems

Answer 43

Removal of brain abnormalities that are causing the seizures ■ Surgeon maps areas of the cortex that are essential for language, motor, and sensory function. Deep Brain Stimulation ■ Stimulation of the vagus nerve or specific brain structure in focal seizures can desynchronize the EEG

Answer 44

Ketogenic Diet ■ Typically used in children with drug resistant epilepsy Switches the bodies primary energy source from glucose to ketones – Ketones are created by the liver from fats ■ Possible that ketones are directly responsible for seizure reduction? ■ Increase mitochondria production? ■ ATP from glycolysis normally inhibits the K+ channel?

Answer 45

``` ■ Neuroplasticity robust throughout life ■ Lack of brain atrophy ■ Only minor structural changes to neurotransmission ■ “benign forgetfulness of the elderly ■ Neurotransmitter levels do not decrease significantly with age ```

Answer 46

■ Loss of global cognitive ability | ■ Syndrome- does not arise from a singular cause

Answer 47

``` Mini-mental status exam ■ Normal: 25 or higher ■ Mild impairment: 21-24 ■ Moderate impairment: 10-20 ■ Severe impairment: <10 ```

Answer 48

Most common dementia in those under 65 years of age ■ Deterioration of the frontal lobe Changes in social and personal behavior – Apathy and social withdraw – Lack of inhibition (stealing, speeding, disinhibited sexual drive) – Compulsive behaviors – Loss of speech fluency- cannot articulate language but can fully comprehend it – Loss of executive function- decreased ability to plan and organize tasks

Answer 49

Memories are strengthened through long-term potentiation: The more times a memory moves through the cortex- MLT pathway, the stronger it becomes – Strengthened synapse due to increased AMPA insertion Memories are lost through long-term depression: ■ Low stimulation of a neuron leads to decreased AMPA receptors – increased difficult to trigger the neuron

Answer 50

Predominant form of dementia AD symptomology aligns with deteriorative progression

Answer 51

You have declarative (things you have to think about) and non declarative memory(things you dont, reflexes, not hippocampus dependent

Answer 52

``` Story telling requires semantic and episodic memories to be brought together Declarative memories thought to be stored in the cortex ■ Semantic memories are associated with the region responsible for the task ■ Information must be brought together to tell a story – Cortical-medial temporal lobe network ```

Answer 53

■ Amyloid Plaques – extracellular ■ Neurofibrillary tangles – intracellular

Answer 54

``` ■ Long hollow tubes ■ Composed of alpha and beta tubulin ■ Largest cytoskeletal element ■ Compression resistant ■ Dynamic Provides : Motility of vesicles and organelles ```

Answer 55

``` Microtubules stabilizing protein – Holds together microtubule bundles ■ Function dependent on phosphorylation ```

Answer 56

``` ■ 6 isoforms- longest is 441 amino acids in length – Normally phosphorylated at 3 sites – 79 possible phosphorylation sites ```

Answer 57

``` ■ Hyperphosphorylation of tau (seen in AD) disrupts microtubule integrity ■ Once microtubules breakdown paired helical fibrils (PHFs) are formed – Insoluble aggregates Tau hyperphosphorylation disrupts axonal transport ```

Answer 58

``` ■ First described by Rudolf Virchow – Starch like structures – Waxy ■ 1984: the amino acid structure of the plaques was determined – Amyloid beta (Ab) peptides clustered together ```

Answer 59

``` Ab derived from processing of APP APP (amyloid precursor protein) – Large transmembrane glycoprotein – Cleaved by three different secretases (alpha, beta, and gamma) ```

Answer 60

Incorrectly uses alpha-secretase to gamma-secretase (its nonamyloidogenic

Answer 61

``` Ab40 and Ab42 are hydrophobic peptides – Upon cleavage, these peptide form insoluble aggregates – 42 more hydrophobic and more toxic ```

Answer 62

``` ■ Gene for APP found on Did you know… the 21st chromosome – DS patients have heightened accumulation of Ab42 at a younger age ```

Answer 63

``` Application of Ab oligomers on hippocampal sections impairs neurotransmission – Decrease LTP – Increase LTD ■ Increase neuronal activity increases the release of Ab ■ Negative feedback loop – Small amounts not as harmful, pathological amounts lead to synaptic death ■ High concentrations of Ab42 leads to inflammation ```

Answer 64

``` g-secretase plays an important role in Notch signaling – Signaling pathway in development and cell polarity generation ■ Possible Notch was the only intended substrate and Ab is erroneous ```

Answer 65

``` Ab42 acts like a prion and causes further misfolding and aggregation of APP cleavage products – Shown in mouse models of the disease ```

Answer 66

■ Late-onset – 80-90% of all cases – Unclear of there is a genetic component ■ Early-onset – Before the age of 60 – Most rapid progression – Most are familial ■ Familial – <5% of all cases – Normally affects individuals in early 40s – Associated genes found on Chromosome 1, 14, and 21

Answer 67

``` Received FDA accelerated approval ■ Antibody targeting amyloid plaques – Successfully shown to reduce plaques in patients – Two phase 3 clinical trials- one met the primary endpoint and the other did not ■ Annual price tag set at $56,000 ```

Answer 68

■ Longitudinal study assessing risk factors and development of dementia ■ 1- lesions to the brain speed cognitive impairment ■ 2- greater idea density decreases risk ■ 3- Neurofibrillary tangles most closely associated with clinical diagnosis of AD ■ 4- “idea density” correlates with disease

Answer 69

beta-secretase inhibitors gamma-secretase inhibitors AB aggregation inhibitors immunotherapy

Answer 70

Apolipoprotein E (ApoE) ■ APOE2- protective against AD ■ APOE3- most frequent in Caucasians ■ APOE4- risk factor for AD – 40-60% individuals with one allele will develop late-onset AD APOE binding to its receptor has been associated with increased APP transcription – APOE4 binds more tightly to the receptor that APOE2 ■ Can decreasing the affinity of binding diminish disease progression?

Answer 71

``` ■ One possible explanation: – APOE2- strengthens and protects BBB – APOE4- alters tight junctions and make BBB more leaky ```

Exam 1 Flashcards

(95 cards)