CNS development, Pharmacology of CNS Flashcards

1
Q

What does the process of gastrulation give us?

A

Three germ layers

  • ectoderm
  • mesoderm
  • endoderm
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2
Q

What are the derivates of ectoderm at the end of development?

A
CNS
PNS
Sensory epithelium of ear, nose and eye
Epidermis, hair and nails 
Subcutaneous, mammary and pituitary glands
Teeth enamel
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3
Q

Describe the development of the notochord from the primitive node.

A

A tube extends from the primitive node, under the ectoderm in the opposite direction to the primitive streak
The tube forms first the axial process, then the notochordal process and finally the notochord
Forms in a transient patterning structure mediated by molecular signalling and controlling the direction of embryonic folding

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4
Q

What is the relationship of the notochord with their underlying ectoderm?

A

Inductive relationship

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5
Q

What causes the thickening of the overlying ectoderm (creates the neural plate)?

A

The appearance of the notochord and mesoderm

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6
Q

What do the cells of the neural plate make up?

A

Neuroectoderm - initial event in the process of neutralisation

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7
Q

What happens to the neural plate once it has been formed?

A

It lengthens and the lateral edges elevate, forming neural folds and a depressed mid region forms the neural groove
The folds approach each other in the midline and then fuse, forming the neural tube

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8
Q

What does the bending of the neural plate depend on?

A

Intrinsic factors- cytoskeleton - stage of the cell cycle

Extrinsic factors - adhesion points, e.g. Within notochord, surface ectoderm

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9
Q

What are the four stages of neurulation?

A

Shaping
Folding
Elevation
Convergence

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10
Q

What cells are present under the neural folds of the neural plate, and aid the elevation and convergence?

A

Neural crest cells

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11
Q

Describe the signalling that occurs in neurulation.

A

Upregulation of fibroblast growth factor and inhibition of BMP-4 causes induction of the neural plate
Chordin and Noggin (BMP-4 antagonists) are expressed

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12
Q

How does the neural tube close?

A

The neural plate switches from E-Caherin expression to N-cadherin expressionThis allows the two neural crests to recognise each other as the same tissue and fuse

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13
Q

What do the neural crest cells give rise to?

A

Melanocytes
Odontoblasts
Tracheal cartilage Enterochromaffin cells
Laryngeal cartilage Parafollicular cells
All ganglia/adrenal medulla
Spiral membrane
Schwann cells

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14
Q

Describe two problems which can arise from a disruption in the migration of neural crest cells?

A

Treacher Collins syndrome- underdevelopment of zygomatic bones and ears - mutation in TCOF 1 gene
Di - George syndrome - cleft palate, cardiac abnormalities, abnormal facies and thymic aplasia

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15
Q

How and when does fusion of the neural tube occur?

A

Fusion begins in the cervical region and proceeds in caudal and cephalic directions Closure occurs in week 4

  • anterior end by day 25
  • posterior end by day 27
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16
Q

What are the open ends of the neural tube called?

A

The anterior and posterior neuropore - they connect with the overlying amniotic sac

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17
Q

What are neuroblasts?

A

These are what the neuroepithelial cells give rise to once the neural tube has closed
They form the mantle layer- becomes the grey matter of the spinal cord

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18
Q

What is the marginal layer of the neural tube?

A

The outer layer of the neural tube, containing nerve fibres emerging from the neuroblasts in the mantle layer- myelinated not of nerve fibres
- White matter of the spinal cord

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19
Q

What is the space in the middle of the neural tube called, and what does it become?

A

It’s called the sulcus limitans, and eventually becomes the central canal

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20
Q

What is the name of the cells surrounding the sulcus limitans

A

Neuroepithelial cells

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21
Q

What is the name for the mantle layer in the posterior neural tube?

A

Alar plate - becomes the dorsal sensory horn

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22
Q

What is the name for the mantle layer in the anterior neural tube?

A

Basal plate - becomes the ventral motor horn

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23
Q

How do the motor axons grow from the spinal cord?

A

They grow straight out of neurons in the basal plate- become ventral root fibres- carry motor innervation

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24
Q

How do sensory axons develop?

A

Neurons in the dorsal root ganglia extend towards the dorsal horn and the periphery - will become the dorsal root fibres- carry sensory innervation

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25
Q

What week does brain development occur in?

A

Week 3

- 3 brain vesicles are present

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26
Q

What are the names of the initial 3 primary brain vesicles?

A

Forebrain - prosencephalon
Midbrain - mesencephalon
Hindbrain - rhombencephalon

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27
Q

What is the flexure that is formed in the mesencephalon?

A

Cephalic flexure - the head fold - bends convex dorsally

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28
Q

What is the name of the flexure in the rhombencephalon?

A

Pontine flexure - bends convex ventrally

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29
Q

What is the flexure between the rhombencephalon and the spinal cord?

A

Temporary - between weeks 5 and 7- convex dorsally

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30
Q

What are the divisions of the 3 primary brain vesicles?

A

Prosencephalon - telencephalon- diencephalon

Mesencephalon stays the same

Rhombencephalon - metencephalon - myelencephalon

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31
Q

When do the 3 primary brain vesicles divide?

A

Week 5- 5 part brain appears

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32
Q

What are the derivates of the telencephalon?

A

Cerebrum

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33
Q

What are the derivates of the diencephalon?

A

Eye cup
Hypothalamus
Epithalamus
Thalamus

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34
Q

What are the derivates of the mesencephalon?

A

The midbrain

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35
Q

What are the derivates of the metencephalon?

A

Pons and the cerebellum

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36
Q

What are the derivates of the myelencephalon?

A

Medullary oblongata

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37
Q

What are the neural tube defects that arise if there is a failure in the anterior and posterior neuropores?

A

Anterior neuropore failure - anencephaly

Posterior neuropore failure - spina bifida (most commonly in the lumbrosacral region)

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38
Q

What are the three types of spina bifida?

A

Spina bifida occulta

Meningocele

Myelomeningocele

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39
Q

Which cerebral abnormality is associated with spina bifida?

A

Hydrocephalus - water on the brain- raised intracranial pressure- large head shape

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40
Q

What are mesenchymal cells?

A

The are epithelial cells that have made the E-cadherin to N-cadherin transition - epithelial to mesenchymal transition

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41
Q

What do the meninges develop from?

A

The mesenchymal cells and neural crest cells

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42
Q

When do the meninges develop?

A

Days 20-35 as the mesenchymal and neural crest cells migrate around the neural tubule

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43
Q

What are the initial structures formed in meningeal development?

A

External layer - dura materInternal layer - arachnoid and pia maters
Fluid filled spaces - the subarachnoid space

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44
Q

Where is CSF made?

A

Made in the choroid plexuses in the brain ventricles

45
Q

How does the choroid plexus develop?

A

Develops where the pia mater and empendyma come into direct contact - e.g. The roof of the fourth ventricle

46
Q

In what condition does CSF build up in the head?

A

Hydrocephalus caused by spina bifida cystica - due to obstruction of the foramen magnum by the cerebellum

47
Q

How is hydrocephalus treated?

A

Relief of ICP

CSF pressure by shunting fluid

48
Q

What is the function of CSF in the skull?

A

Floats the brain a little, providing cushioning and buoyancy - making sure it’s weight doesn’t crush the cranial nerves at the base of the skull

49
Q

What is empendyma?

A

Thin epithelium-like cells that line the inside of the ventricles and the central canal of the spinal cord It’s involved in the production of CSF

50
Q

Describe notochord formation.

A

Notochordal process grows out of the primitive node as a rod of cells from the mesoderm and migrate cranially
Notochordal process forms as a hollow tube
This then flattens to become the notochordal plate
This happens because the ventral floor of the notochordal process fuses with the endoderm below, assuming a flat shape
The plate then detaches from the endoderm and re-rolls into a solid rod called the notochord

51
Q

What do meninges arise from?

A

All arise from the mesoderm- meninges in the anterior skull arise from neural crest cells- meninges in trunk and caudal head regions arise from paraxial mesoderm

52
Q

Which order do the meninges arise?

A

Pia mater first - day 24
Dura mater second - day 45
Arachnoid mater last - day 57

53
Q

When does the developing eye appear?

A

Day 22 - as a pair of shallow grooves

54
Q

What do the initial grooves for the eyes form?

A

They form outgrowths from the diencephalon of the forebrain called optic vesicles

55
Q

Describe optic vesicles.

A

They are in contact with the surface ectoderm and induce changes necessary for lens formation

56
Q

What are lens placodes?

A

They are cells of the ectoderm that lie over the optic vesicles. When stimulated they become columnar and invaginate - this forced invagination of the optic vesicles- double walled cup

57
Q

Which artery supplies the lens and the developing retina, and how does it reach them?

A

Hyaloid artery (branch of the ophthalmic artery)

  • grooves form on the ventral side of the optic cup, forming a choroidal fissure
  • this is where the artery travels
58
Q

Describe the development of the lens of the eye.

A

The lens is initially hollow, derived from surface ectoderm
Cells of the lens elongate anteriorly to form long lens fibres which arrange in a laminar pattern to form a transparent lens

59
Q

<p>What happens to each wall of the 'double walled cup'?</p>

A

The outer layer becomes the pigmented layer of the retina
The inner layer becomes the nervous layer of the retina (rods, cones and cell bodies of neurons)
Space between the layers disappears as axons grow from the optic nerve (but there is still a potential weakness)

60
Q

How do the iris and ciliary body develop?

A

At the rim of the optic cup, both layers of the retina give rise to the iris and ciliary bodies
The ciliary body produces aqueous humour

61
Q

Describe the development of the optic nerve.

A

1) optic cup is connected to the brain by the optic stalk (Hyaloid vessels in the choroid fissure) - 6th week
2) Inner and outer layers fuse and the cavity of the stalk disappears - inner layer cells provide a network of neuroglia that support the optic nerve fibres - 7th week
3) The optic stalk becomes the optic nerve - Hyaloid artery and vein become the central artery and vein of the retina - 9th week

62
Q

Describe the development of the eyeball.

A

The mesenchymal around the optic cup condenses to form the layers of the eyeball - the sclera and the choroid
The most anterior part of the cornea becomes transparent
Spaces develop in the mesenchyme between the cornea and the lens (anterior chamber)

63
Q

Describe the development of the eyelids.

A

Folds of ectoderm with mesenchyme between them that grow over the cornea
Fuse and enclose a conjunctival sac anterior to the corneaInner layer becomes the conjunctiva and fuses with the cornea over the iris
Lacrimal glands form as ectodermal buds from the upper conjunctival sac into the surrounding mesoderm
Eyelids separate again between the 5th and 7th month in utero

64
Q

What is the key regulatory molecule for eye development?

A

PAX-6- expressed in the anterior neural plate before neurulation begins

65
Q

What is the molecule responsible for eye field separation?

A

SHH - signalling molecule that upregulates PAX2 in the optic stalks and restricts PAX6 to the optic cup and lens

66
Q

List and describe some developmental eye conditions.

A

Microphtalmia - eyeball is too small (genetic/FAS)
Anopthalmia - absense of eye caused by failure of the optic vesicle to develop (genetic/infection)
Cyclopia - single eye caused by failure of the prosencephalon to divide the orbits of the eye (mutations in SHH)
Choloboma iridis - failure of the choroid fissure to close, causing a cleft in the iris
Congenital detachment of the retina - failure of fusion of the inner and outer layers
Congenital cataracts - lens is opaque due to abnormal fibre development (genetic/infection between weeks 4-7)

67
Q

What are the names of the plates that connect the left and right basal and alar sinuses to each other?

A

Basal - floor plate

Alar - roof plate

68
Q

Name some fast acting drugs on the CNS?

A

Anaesthetics
Nicotine
Cocaine

69
Q

Name some slow acting drugs on the CNS.

A

Antidepressants

Antipsychotics- several weeks before beneficial effects occur

70
Q

What is the function of the blood brain barrier?

A

Maintain a constant environment
Protect the brain from foreign substances
Protect the brain from peripheral transmitters

71
Q

Name an area of the brain located outside the BBB?

A

Area postrema - vomit reflex

72
Q

Name some things that can damage the BBB.

A

Hypertension
Infection
Trauma

73
Q

What can happen if the BBB is compromised?

A

Substance can enter the CNS and cause toxicity- even prescribed drugs can become dangerous

74
Q

Which drugs of the CNS are administered enterally and parenterally?

A

Enteral - lipophylic drugs
Parenteral - invasive routes (intrathecal) - meningitis antibiotics - opiate analgesics - regional anaesthetic (epidural)

75
Q

Name some approaches that can be administered to aid drug entry to the CNS.

A

Prodrugs (L-DOPA)
Carrier molecules
Transient BBB disruption (mannitol)

76
Q

Define anaesthetic agents

A

Drugs used to produce surgical anaesthesia

77
Q

Give some examples of analgesic agents.

A

Halothane
Desflurane
Esflourane
Propofol

78
Q

Define anxiolytics and sedatives

A

Drugs that cause sleep and reduce anxiety

Synonymous with - hypnotics, sedatives, minor tranquillisers

79
Q

Give some examples of sedatives.

A

Barbiturates

Benzodiazepines

80
Q

Define antipsychotic drugs.

A

Drugs that are effective in relieving the symptoms of schizophrenic illness (a.k.a. Neuroleptics, antischizophrenics, major tranquillisers)

81
Q

Gives some examples of antipsychotics drugs.

A

Clozapine

Chlorpromazine

Haloperidol

82
Q

Define anti-depressive drugs.

A

Drugs that alleviate the symptoms of depressive illness

Can also be known as thymoleptics

83
Q

Give some examples of anti-depressive drugs.

A

Monoamine oxidase inhibitor (phenelzine)
Tricyclic antidepressants (imipramine)
SSRIs (fluoxetine)
Acute (ketamine)

84
Q

Define analgesic drugs.

A

Drugs used clinically for the alleviation of pain (painkillers)

85
Q

Give some examples of some analgesics.

A

NSAIDs
Opiates
Carbamazepine

86
Q

Define psychomotor stimulants.

A

Drugs that cause wakefulness and euphoria (psychostimulants)

87
Q

Give some examples of psychomotor stimulants.

A

Methyphenidate (Ritalin)
Amphetamine (vyvanse)
Cocaine
Caffeine

88
Q

Define psychotomimetic drugs.

A

Drugs that cause disturbance of perception and of behaviour that can’t simply be characterised as sedative or stimulant effects.
Also known as hallucinogenic and psychodyspletics

89
Q

Give some examples of psychotomimetic drugs.

A

LSD
Marijuana
Mescaline
Phencyclidine

90
Q

Define cognition enhancer drugs.

A

Drugs that improve memory and cognitive performance

91
Q

Give some examples of cognition enhancer drugs.

A

Tacrine

Donepezil

92
Q

Name some CNS drugs that don’t fit into a specific category.

A

Anti-Parkinson drugs
Anti-epilepsy drugs
Drugs to treat addiction and dependence
Lithium

93
Q

List the neurological diseases that CNS drugs can be used to treat.

A
Epilepsy 
Dementia
Pain
Movement disorders (PD, HD)
Pain (neuropathic)
Stroke
94
Q

List the psychiatric diseases that CNS drugs can be used to treat

A

Depression
Schizophrenia
Anxiety
Sleep disorders

95
Q

List some other diseases that CNS drugs can help to treat.

A

Motion sickness
Fever
General anaesthetic

96
Q

What is the function of dopamine in the nigrostriatal system, and what do disorders of it cause.

A

Motor control Parkinson’s

97
Q

What is the function of dopamine in the mesolimbic/cortical system, and what do disorders of it cause.

A

Behavioural effects

Schizophrenia

98
Q

What is the function of dopamine in the tuberohypopyseal system, and what do disorders of it cause.

A

Suppresses prolactin release

Galactorrhea

99
Q

What is the function of dopamine in the medulla, and what do disorders of it cause.

A

Vomit response

Vomiting

100
Q

What are the main three characteristics of Parkinson’s disease?

A

Rigidity
Tremor
Bradykinesia

101
Q

What are the possible causes of degeneration of the nigrostriatal system/Parkinson’s disease?

A

Genetics - Parkin and other risk genes
Age, can accompany dementia
Infection, ischaemia
Environmental risk factors - toxins, herbicides, pesticides

102
Q

What therapies are used in Parkinson’s?

A

Therapies that enhance dopaminergic signalling in the pathway

  • replace dopamine (L-DOPA)
  • mimic the action of dopamine (D2/3 agonists - bromocriptine)
  • reduce breakdown of dopamine (MAOIs - selegiline)
  • increase dopamine release from remaining fibres (amantadine)
103
Q

What are the positive and negative symptoms of schizophrenia?

A

Positive - delusions, hallucinations, thought disorders

Negative - social withdrawal, emotional flattening, reduced drive, poverty of speech, inability to feel pleasure

104
Q

Describe the pathophysiology of schizophrenia briefly.

A

Environmental and genetic factors leading to abnormalities of the cerebral cortex
Alterations in various neurotransmitter systems (dopamine, 5HT, glutamate, GABA)

105
Q

What is the dopamine theory?

A

Development of psychotic symptoms can be associated with abnormalities in the mesocortical/limbic pathways
Drugs which deplete dopamine have an antipsychotic action
Drugs which release dopamine generate psychotic symptoms - needs to be a balance

106
Q

What are the possible treatment options for schizophrenia?

A

All antipsychotics are currently D2 receptor blockers - typical (old) drugs

  • chlorpromazine and haloperidol
  • atypical (newer) drugs
  • clozapine and asenapine
107
Q

What are the possible side effects of Parkinson’s treatment?

A
Schizophrenia symptoms (too much dopamine in mesolimbic)
Nausea - caused by peripheral breakdown of dopamine 
Dopamine dysregulation syndrome - self control problems
108
Q

What are the possible side effects of Schizophrenic treatment?

A
Parkinson effects (not enough dopamine in the nigrostriatal)
Sedative effect 
Prolactin secretion (not enough dopamine in the tuberohypopyseal) - breast swelling and galactorrhoea