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mental health + neurobiology > neuroepigenetics > Flashcards

neuroepigenetics Flashcards

1
Q

how is the epigenome impactful?

A

Leave a footprint on our genes by altering the epigenome and subsequently the expression pattern of our genes

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2
Q

what does epigenome provide?

A

plasticity

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3
Q

how is epigenetic formed?

A

gene that is transcriptionally inactive (suppressed) is condensed and packed very tightly around the core histone proteins

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4
Q

what transcription does the modification histone tail suppress?

A

De-acetylation
H3K27

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5
Q

what transcription doe the modification histone tail activate?

A

Acetylation of histone 3 lysine 27
H3K27ac

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6
Q

what transcription does the modification DNA(CpG dinucleotide) suppress ?

A

methylated cytosine
5-mC

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7
Q

what transcription does the modification DNA activate?

A

un-methylated cytosine
C

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8
Q

histone acetyltransferease(HAT)

A

relaxed chromatin (euchromatin) transcription
-there is transcription

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9
Q

deacteylation enzyme: histone deacetyltransferase (HDAC)

A

-includes compact chromatin(heterochromatin)
-there is no transcription here

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10
Q

what is neurogenic genes

A

epigenetic mechanism, is creating plasticity in function of different nervous system cells by altering the expression of genes based on which genes are needed for their function

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11
Q

Neuron specific regulatory reigon

A

having epithelial which are specific meaning they are methylated so genes will be active

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12
Q

neurogenic genes

A

active in neurons, become methylated in glial cells and inactive while they remain unmethylated and active in neuron cells

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13
Q

does plasticity in response stop?

A

response doesn’t stop after embryogenesis and is not only restricted to cell regeneration and differentiation
-it does continue throughout life

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14
Q

Neuroplasticity

A

ability of the brain to recognise itself and to change in response to our environment and in response to our thoughts

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15
Q

what does neuroplasticity allow?

A

neurons to compensate for injury and disease and to adjust and adapt to new activities in response to new situations or to changes in their environment

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16
Q

what is synaptic connection?

A

in the brain which sometimes are referred to as the ‘wiring diagram’ of the brain (map of functional connectivity)

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17
Q

what is synaptic plasticity?

A

change that occurs at synapses, the junctions between neurons that allow them to communicate

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18
Q

what 4 things are connectome changed by?

A

1.rewiring
2.reconnect
3.retracting
4.regeneration

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19
Q

Rewiring

A

strengthening or weakening connections

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20
Q

Reconnect

A

creating and eliminating synapses

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21
Q

Retracting

A

grow and retracting branches and connections (Pruning)

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22
Q

Regeneration

A

new neurons are generated

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23
Q

what do neuronal network and plasticity change as a function of ?

A

function of experience and the environment

24
Q

what does altered neural connectivity lead to?

A

distinct transcriptional activation of genes in short term or long-term manner

25
Q

what are the modifications in neuronal epigenome responsible for?

A

lasting reprogramming of gene expression which gives our brain the ability to undergo neuronal differentiation, maturation and plasticity (rewiring, reconnect, regenerate, pruning).

26
Q

if there is an abnormal change in the connective architecture what are the 4 examples of this?

A

1.addiction
2.neurological
3.developmental disorders
4.neurodegeneration

27
Q

what are examples abnormal changes changes in the connective architecture disorders?

A

Autism
Attention deficit hyperactivity disorder (ADHD)
Schizophrenia
Amyotrophic lateral sclerosis
Alzheimer’s disease
Parkinson’s disease

28
Q

HDAC-histone de acetyltransferase

A

repressed chromatin

29
Q

HAT- enzyme acetyl transferase

A

active chromatin

30
Q

what is the 5-mC (5-methylcytosine?

A

Marker of transcriptionally inactive gene

31
Q

What does HDAC do to the 5-mC?

A

Remove acetyl groups from histone tail leading to gene inactivation

32
Q

what does DNMT do to the 5-mC?

A

Adds methyl groups to cytosine bases

33
Q

what is H3K27me3 ?

A

repressed gene

34
Q

what does MeCP2 recognising?

A

recognises methylated regions and binds to them - promotes chromatin condensation by recruiting HDAC to remove acetyl group.

35
Q

what does enzyme acetyl transferase (HAT ) have?

A

C (unmethylated cytosine): Marker of transcriptionally active gene

36
Q

what does HAT do to the C?

A

Adds acetyl groups to histone tail leading to gene activation

37
Q

what is H3K4me3 (Histone 3 lysine 4 trimethylation)?

A

Active gene

38
Q
A
39
Q
A
40
Q

what is rett syndrome?

A

X-linked neurodevelopmental disorder that affects brain development, resulting in severe mental and physical disabilities

41
Q

how does Rett syndrome impact neurones?

A

1.Impacts neuron differentiation
2.formation of different neurons in the brain

42
Q

what does rett syndrome do to the synaptic connections and plasticity?

A

impacts formation of synaptic connections and plasticity

43
Q

what is the gene responsible for Rett syndrome?

A

MeCP2

44
Q

what 4 things is MeCP2 critical for?

A

1.neuronal maturation, 2.synaptogenesis
3.synapse function (neurotransmitter release) 4.neuronal connectivity (Connectome)

45
Q

what is the transcription factor MeCP2 important for?

A

controlling gene expression through regulation of epigenetic markers.

46
Q

how does MeCP2 induce chromatin condensation?

A

by binding to methylated cytosines and recruiting HDACs - transcription inactivation.

47
Q

what does the mutation in MeCP2 impact?

A

1.length and node of astrocytes
2.this impacts on formation of brain connections and function

48
Q

when the MeCP2 function is lost how can this impact the brain regions?

A

1.The brain is smaller than normal
2.The neurons exhibit reduced dendritic complexity
3.Expression of synaptic proteins are reduced
4.Astrocytes have shorter and less complex/node dendrites

49
Q

what are 2 features of the synaptic protein?

A

1.regulation of neurotransmitter release
2 participation in the early development of neurons

50
Q

parkinsons disease

A

chronic, progressive neurodegenerativecondition resulting from the loss of the dopamine neurons of the substantia nigra

51
Q

familial Parkinson’s disease

A

15% of people with Parkinson disease have a family history of this disorder

52
Q

which mutations are caused by familial cases of Parkinson’s ?

A

LRRK2
PARK7
PINK1
PRKN
SNCA

53
Q

alpha-synuclein protein

A

SNCA makes the protein alpha-synuclein.

54
Q

how is the alpha-synuclein protein impacted in familial PD?

A

mutated SNCA, this protein gathers in clumps called Lewy bodies.
Lewy bodies appear in dead or dying dopamine-producing neurons
Mutation in this gene follow the autosomal dominant pattern of inheritance.

55
Q

what levels does mutated SNCA gene reduce?

A

methylation levels

56
Q

when the mutated SNCA gene reduces methylation levels what does this lead to?

A

increased expression of the gene and accumulation of the alpha-synuclein protein, and formation of the Lewy bodies in dopamine neurons and their apoptosis.

57
Q

what happens when there is a formation of Lewy bodies?

A

leads to lower number level of dopamine and changes in movement that is seen in PD

mental health + neurobiology (45 decks)

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