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P2 Head, Neck and Neuro > CNS development, Pharmacology of CNS > Flashcards

CNS development, Pharmacology of CNS Flashcards

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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
What week does brain development occur in?
Week 3 | - 3 brain vesicles are present
26
What are the names of the initial 3 primary brain vesicles?
Forebrain - prosencephalon Midbrain - mesencephalon Hindbrain - rhombencephalon
27
What is the flexure that is formed in the mesencephalon?
Cephalic flexure - the head fold - bends convex dorsally
28
What is the name of the flexure in the rhombencephalon?
Pontine flexure - bends convex ventrally
29
What is the flexure between the rhombencephalon and the spinal cord?
Temporary - between weeks 5 and 7- convex dorsally
30
What are the divisions of the 3 primary brain vesicles?
Prosencephalon - telencephalon- diencephalon Mesencephalon stays the same Rhombencephalon - metencephalon - myelencephalon
31
When do the 3 primary brain vesicles divide?
Week 5- 5 part brain appears
32
What are the derivates of the telencephalon?
Cerebrum
33
What are the derivates of the diencephalon?
Eye cup Hypothalamus Epithalamus Thalamus
34
What are the derivates of the mesencephalon?
The midbrain
35
What are the derivates of the metencephalon?
Pons and the cerebellum
36
What are the derivates of the myelencephalon?
Medullary oblongata
37
What are the neural tube defects that arise if there is a failure in the anterior and posterior neuropores?
Anterior neuropore failure - anencephaly Posterior neuropore failure - spina bifida (most commonly in the lumbrosacral region)
38
What are the three types of spina bifida?
Spina bifida occulta Meningocele Myelomeningocele
39
Which cerebral abnormality is associated with spina bifida?
Hydrocephalus - water on the brain- raised intracranial pressure- large head shape
40
What are mesenchymal cells?
The are epithelial cells that have made the E-cadherin to N-cadherin transition - epithelial to mesenchymal transition
41
What do the meninges develop from?
The mesenchymal cells and neural crest cells
42
When do the meninges develop?
Days 20-35 as the mesenchymal and neural crest cells migrate around the neural tubule
43
What are the initial structures formed in meningeal development?
External layer - dura materInternal layer - arachnoid and pia maters Fluid filled spaces - the subarachnoid space
44
Where is CSF made?
Made in the choroid plexuses in the brain ventricles
45
How does the choroid plexus develop?
Develops where the pia mater and empendyma come into direct contact - e.g. The roof of the fourth ventricle
46
In what condition does CSF build up in the head?
Hydrocephalus caused by spina bifida cystica - due to obstruction of the foramen magnum by the cerebellum
47
How is hydrocephalus treated?
Relief of ICP | CSF pressure by shunting fluid
48
What is the function of CSF in the skull?
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
What is empendyma?
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
Describe notochord formation.
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
What do meninges arise from?
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
Which order do the meninges arise?
Pia mater first - day 24 Dura mater second - day 45 Arachnoid mater last - day 57
53
When does the developing eye appear?
Day 22 - as a pair of shallow grooves
54
What do the initial grooves for the eyes form?
They form outgrowths from the diencephalon of the forebrain called optic vesicles
55
Describe optic vesicles.
They are in contact with the surface ectoderm and induce changes necessary for lens formation
56
What are lens placodes?
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
Which artery supplies the lens and the developing retina, and how does it reach them?
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
Describe the development of the lens of the eye.
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

What happens to each wall of the 'double walled cup'?

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
How do the iris and ciliary body develop?
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
Describe the development of the optic nerve.
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
Describe the development of the eyeball.
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
Describe the development of the eyelids.
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
What is the key regulatory molecule for eye development?
PAX-6- expressed in the anterior neural plate before neurulation begins
65
What is the molecule responsible for eye field separation?
SHH - signalling molecule that upregulates PAX2 in the optic stalks and restricts PAX6 to the optic cup and lens
66
List and describe some developmental eye conditions.
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
What are the names of the plates that connect the left and right basal and alar sinuses to each other?
Basal - floor plate | Alar - roof plate
68
Name some fast acting drugs on the CNS?
Anaesthetics Nicotine Cocaine
69
Name some slow acting drugs on the CNS.
Antidepressants | Antipsychotics- several weeks before beneficial effects occur
70
What is the function of the blood brain barrier?
Maintain a constant environment Protect the brain from foreign substances Protect the brain from peripheral transmitters
71
Name an area of the brain located outside the BBB?
Area postrema - vomit reflex
72
Name some things that can damage the BBB.
Hypertension Infection Trauma
73
What can happen if the BBB is compromised?
Substance can enter the CNS and cause toxicity- even prescribed drugs can become dangerous
74
Which drugs of the CNS are administered enterally and parenterally?
Enteral - lipophylic drugs Parenteral - invasive routes (intrathecal) - meningitis antibiotics - opiate analgesics - regional anaesthetic (epidural)
75
Name some approaches that can be administered to aid drug entry to the CNS.
Prodrugs (L-DOPA) Carrier molecules Transient BBB disruption (mannitol)
76
Define anaesthetic agents
Drugs used to produce surgical anaesthesia
77
Give some examples of analgesic agents.
Halothane Desflurane Esflourane Propofol
78
Define anxiolytics and sedatives
Drugs that cause sleep and reduce anxiety | Synonymous with - hypnotics, sedatives, minor tranquillisers
79
Give some examples of sedatives.
Barbiturates | Benzodiazepines
80
Define antipsychotic drugs.
Drugs that are effective in relieving the symptoms of schizophrenic illness (a.k.a. Neuroleptics, antischizophrenics, major tranquillisers)
81
Gives some examples of antipsychotics drugs.
Clozapine Chlorpromazine Haloperidol
82
Define anti-depressive drugs.
Drugs that alleviate the symptoms of depressive illness | Can also be known as thymoleptics
83
Give some examples of anti-depressive drugs.
Monoamine oxidase inhibitor (phenelzine) Tricyclic antidepressants (imipramine) SSRIs (fluoxetine) Acute (ketamine)
84
Define analgesic drugs.
Drugs used clinically for the alleviation of pain (painkillers)
85
Give some examples of some analgesics.
NSAIDs Opiates Carbamazepine
86
Define psychomotor stimulants.
Drugs that cause wakefulness and euphoria (psychostimulants)
87
Give some examples of psychomotor stimulants.
Methyphenidate (Ritalin) Amphetamine (vyvanse) Cocaine Caffeine
88
Define psychotomimetic drugs.
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
Give some examples of psychotomimetic drugs.
LSD Marijuana Mescaline Phencyclidine
90
Define cognition enhancer drugs.
Drugs that improve memory and cognitive performance
91
Give some examples of cognition enhancer drugs.
Tacrine | Donepezil
92
Name some CNS drugs that don't fit into a specific category.
Anti-Parkinson drugs Anti-epilepsy drugs Drugs to treat addiction and dependence Lithium
93
List the neurological diseases that CNS drugs can be used to treat.
``` Epilepsy Dementia Pain Movement disorders (PD, HD) Pain (neuropathic) Stroke ```
94
List the psychiatric diseases that CNS drugs can be used to treat
Depression Schizophrenia Anxiety Sleep disorders
95
List some other diseases that CNS drugs can help to treat.
Motion sickness Fever General anaesthetic
96
What is the function of dopamine in the nigrostriatal system, and what do disorders of it cause.
Motor control Parkinson's
97
What is the function of dopamine in the mesolimbic/cortical system, and what do disorders of it cause.
Behavioural effects | Schizophrenia
98
What is the function of dopamine in the tuberohypopyseal system, and what do disorders of it cause.
Suppresses prolactin release | Galactorrhea
99
What is the function of dopamine in the medulla, and what do disorders of it cause.
Vomit response Vomiting
100
What are the main three characteristics of Parkinson's disease?
Rigidity Tremor Bradykinesia
101
What are the possible causes of degeneration of the nigrostriatal system/Parkinson's disease?
Genetics - Parkin and other risk genes Age, can accompany dementia Infection, ischaemia Environmental risk factors - toxins, herbicides, pesticides
102
What therapies are used in Parkinson's?
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
What are the positive and negative symptoms of schizophrenia?
Positive - delusions, hallucinations, thought disorders | Negative - social withdrawal, emotional flattening, reduced drive, poverty of speech, inability to feel pleasure
104
Describe the pathophysiology of schizophrenia briefly.
Environmental and genetic factors leading to abnormalities of the cerebral cortex Alterations in various neurotransmitter systems (dopamine, 5HT, glutamate, GABA)
105
What is the dopamine theory?
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
What are the possible treatment options for schizophrenia?
All antipsychotics are currently D2 receptor blockers - typical (old) drugs - chlorpromazine and haloperidol - atypical (newer) drugs - clozapine and asenapine
107
What are the possible side effects of Parkinson's treatment?
``` Schizophrenia symptoms (too much dopamine in mesolimbic) Nausea - caused by peripheral breakdown of dopamine Dopamine dysregulation syndrome - self control problems ```
108
What are the possible side effects of Schizophrenic treatment?
``` Parkinson effects (not enough dopamine in the nigrostriatal) Sedative effect Prolactin secretion (not enough dopamine in the tuberohypopyseal) - breast swelling and galactorrhoea ```

P2 Head, Neck and Neuro (11 decks)

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