neuroepigenetics Flashcards
how is the epigenome impactful?
Leave a footprint on our genes by altering the epigenome and subsequently the expression pattern of our genes
what does epigenome provide?
plasticity
how is epigenetic formed?
gene that is transcriptionally inactive (suppressed) is condensed and packed very tightly around the core histone proteins
what transcription does the modification histone tail suppress?
De-acetylation
H3K27
what transcription doe the modification histone tail activate?
Acetylation of histone 3 lysine 27
H3K27ac
what transcription does the modification DNA(CpG dinucleotide) suppress ?
methylated cytosine
5-mC
what transcription does the modification DNA activate?
un-methylated cytosine
C
histone acetyltransferease(HAT)
relaxed chromatin (euchromatin) transcription
-there is transcription
deacteylation enzyme: histone deacetyltransferase (HDAC)
-includes compact chromatin(heterochromatin)
-there is no transcription here
what is neurogenic genes
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
Neuron specific regulatory reigon
having epithelial which are specific meaning they are methylated so genes will be active
neurogenic genes
active in neurons, become methylated in glial cells and inactive while they remain unmethylated and active in neuron cells
does plasticity in response stop?
response doesn’t stop after embryogenesis and is not only restricted to cell regeneration and differentiation
-it does continue throughout life
Neuroplasticity
ability of the brain to recognise itself and to change in response to our environment and in response to our thoughts
what does neuroplasticity allow?
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
what is synaptic connection?
in the brain which sometimes are referred to as the ‘wiring diagram’ of the brain (map of functional connectivity)
what is synaptic plasticity?
change that occurs at synapses, the junctions between neurons that allow them to communicate
what 4 things are connectome changed by?
1.rewiring
2.reconnect
3.retracting
4.regeneration
Rewiring
strengthening or weakening connections
Reconnect
creating and eliminating synapses
Retracting
grow and retracting branches and connections (Pruning)
Regeneration
new neurons are generated
what do neuronal network and plasticity change as a function of ?
function of experience and the environment
what does altered neural connectivity lead to?
distinct transcriptional activation of genes in short term or long-term manner
what are the modifications in neuronal epigenome responsible for?
lasting reprogramming of gene expression which gives our brain the ability to undergo neuronal differentiation, maturation and plasticity (rewiring, reconnect, regenerate, pruning).
if there is an abnormal change in the connective architecture what are the 4 examples of this?
1.addiction
2.neurological
3.developmental disorders
4.neurodegeneration
what are examples abnormal changes changes in the connective architecture disorders?
Autism
Attention deficit hyperactivity disorder (ADHD)
Schizophrenia
Amyotrophic lateral sclerosis
Alzheimer’s disease
Parkinson’s disease
HDAC-histone de acetyltransferase
repressed chromatin
HAT- enzyme acetyl transferase
active chromatin
what is the 5-mC (5-methylcytosine?
Marker of transcriptionally inactive gene
What does HDAC do to the 5-mC?
Remove acetyl groups from histone tail leading to gene inactivation
what does DNMT do to the 5-mC?
Adds methyl groups to cytosine bases
what is H3K27me3 ?
repressed gene
what does MeCP2 recognising?
recognises methylated regions and binds to them - promotes chromatin condensation by recruiting HDAC to remove acetyl group.
what does enzyme acetyl transferase (HAT ) have?
C (unmethylated cytosine): Marker of transcriptionally active gene
what does HAT do to the C?
Adds acetyl groups to histone tail leading to gene activation
what is H3K4me3 (Histone 3 lysine 4 trimethylation)?
Active gene
what is rett syndrome?
X-linked neurodevelopmental disorder that affects brain development, resulting in severe mental and physical disabilities
how does Rett syndrome impact neurones?
1.Impacts neuron differentiation
2.formation of different neurons in the brain
what does rett syndrome do to the synaptic connections and plasticity?
impacts formation of synaptic connections and plasticity
what is the gene responsible for Rett syndrome?
MeCP2
what 4 things is MeCP2 critical for?
1.neuronal maturation, 2.synaptogenesis
3.synapse function (neurotransmitter release) 4.neuronal connectivity (Connectome)
what is the transcription factor MeCP2 important for?
controlling gene expression through regulation of epigenetic markers.
how does MeCP2 induce chromatin condensation?
by binding to methylated cytosines and recruiting HDACs - transcription inactivation.
what does the mutation in MeCP2 impact?
1.length and node of astrocytes
2.this impacts on formation of brain connections and function
when the MeCP2 function is lost how can this impact the brain regions?
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
what are 2 features of the synaptic protein?
1.regulation of neurotransmitter release
2 participation in the early development of neurons
parkinsons disease
chronic, progressive neurodegenerativecondition resulting from the loss of the dopamine neurons of the substantia nigra
familial Parkinson’s disease
15% of people with Parkinson disease have a family history of this disorder
which mutations are caused by familial cases of Parkinson’s ?
LRRK2
PARK7
PINK1
PRKN
SNCA
alpha-synuclein protein
SNCA makes the protein alpha-synuclein.
how is the alpha-synuclein protein impacted in familial PD?
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.
what levels does mutated SNCA gene reduce?
methylation levels
when the mutated SNCA gene reduces methylation levels what does this lead to?
increased expression of the gene and accumulation of the alpha-synuclein protein, and formation of the Lewy bodies in dopamine neurons and their apoptosis.
what happens when there is a formation of Lewy bodies?
leads to lower number level of dopamine and changes in movement that is seen in PD
