Neuronal Homeostasis Flashcards
What is meant by a chronic condition and provide some examples
Chronic conditions occur over long periods of time and are often progressive
Some examples of chronic conditions include; Alzheimer’s, Parkinson’s, Huntington’s and Prion’s disease
What are acute diseases and provide some examples
Acute diseases are often injury related and are short term
For example; Spinal cord injurt, Stroke and Traumatic brain injury
Neurodegenerative diseases are around what?
Neuronal dysfunction and neuronal death
LO
- Be familiar with the structure and function of a neurone
- Understand the homeostatic processes within neurones
- Appreciate the problems that neurones face
- Be familiar with the mechanisms by which neurones become dysfunctional in neurodegenerative diseases
What can happen to the brain neuronal circuitry as we age?
- Pruning of synapses/ plasticity
- Degenration e.g., glia or the circuit its self
Think about what in the circuit makes us vulnerable to disease…?
What is meant by synaptic pruning?
Synaptic pruning is a natural process that occurs in the brain between early childhood and adulthood. During synaptic pruning, the brain eliminates extra synapses.
Synaptic pruning is thought to be the brain’s way of removing connections in the brain that are no longer needed.
Neurons are polarised cells, what does this mean and how does this feature help?
Neurones are polarised cells this means that it has parts of it that are different e.g., dendritic structures and other structures
This means they have distinct functional regions: dendrites, soma, axon, and synapse
This helps because it provides a division of labour and helps with directionality (can go the other way in certain circumstances)
What are some of the key features in a neuron?
Soma
Axon
Synapse
Tell me the main roles of a soma
Receives input from other neurones
All housekeeping activities occur here (has nucleus, transcription, translation etc.,)- has high energy demand
Materials destined for distant areas dispatched
(materials= neurotransmitters is one of the key materials synthesised in the cell body for transport into the axon)
Tell me the main roles of axons
Axonal transport of NTs occurs over microtubular tracks
Motor proteins (kinesin and dynein) propel cargo forward (ATP- provided by mitochondria)
Conduct electrical impulses- hence myelinated
AP generated in the axon and is propagated along the axon (helped by myelin and nodes of Ranvier)
Neural filaments and cytoskeleton’s role in the axon?
Tell me the main roles of synapses
- Neuron’s business end
- NTs released to communicate with target (ATP)
- Retrograde signalling
How does the structure of the synapses help with its function?
Structure allows function to occur because has high conc. Of voltage gated Ca2+ channels,
has postsynaptic and presynaptic and auto receptors to regulate and modulate NT release (controlled process)
short synaptic cleft
huge amount of mitochondrial need to generate lots of energy for the high NT release
What is retrograde signalling and what type of information does it transmit?
Retrograde signalling: signalling that goes backwards (post- –> pre-synaptic neuron).
The kind of information that is sent is when it’s requires more NT due to a high demand for it
Signals go back to preserve the circuit
When can retrograde signalling become a problem?
This becomes a problems when an individual has impaired retrograde signalling, then the pre-synaptic neuron may not get the signals it requires to stay alive
Could have something which retrogrades and then causes damage to the structure
Progression of neurodegenerative diseases (less activity in downstream circuit which has a negative effect on upstream circuit)
What is homeostasis important for?
For keeping the systems regulating at an optimal level
Give some examples of homeostatic pathways in neurons
- Ubiquitin proteosome pathway
- Endosomal/ lysosomal system
- Retrograde signalling
Tell me about the ubiquitin proteosome pathway
Ubiquitin proteosome pathway: proteolytic degradation of damaged or misfolded proteins after ubiquitination (UQ added as a tag)
Tell me about the endosomal/ lysosomal system
Endosomal/ lysosomal system: Internalisation of misfolded or abnormal proteins followed by enzymatic degradation
Tell me about retrograde signalling
Retrograde signalling: neurotrophic factors (trophic support) and importins (retrograde injury signalling)
Give an example of some diseases that can occur when these homeostatic mechanisms go wrong
How do these go wrong in diseases and the homeostatic mechanisms aren’t kept at their optimal levels…?
i.e., Stroke and oxygen and glucose levels impaired
At cellular levels the ion channel disruption such as sodium channel dysfunctions where they aren’t activated as easily leaving the individual with a high pain threshold, mitochondrial dysfunction with Parkinson’s disease
The ubiquitin pathway can cause the formation of misfolded proteins. What can these proteins cause to happen and why don’t we want them present? What sort of effects can they cause?
Don’t want misfolded proteins in cytoplasm; these proteins act as a template and causes those proteins which are working normally (naïve proteins) to be converted and start producing the wrong function
(e.g., AD, PD, HD has aggregates of misfolded proteins in the neuron and accumulating becoming bigger. This is bad not only because of conversion of normal proteins but can also get in the way of synaptic transmission and other functions of the neurone).
Many of these misfolded proteins can jump over the synapse into the next cell and cause disruption in cells and their adjacent cells.
What is some evidence of the presence of misfolded proteins?
Evidence of these misfolded proteins are; all these structures have UQ which are saying ‘eat me’ so system is trying to remove them unsuccessfully
Why do the neuronal circuits in the older generation have more proteins being misfolded?
Older circuit in the older generation, have more proteins being misfolded and not the same capacity of the systems. Therefore, is unable to deal with misfolded proteins. At the molecular level it may be overworked or lose function (age related decline in optimal functioning)
What are some of the problems that many neurons face?
Transport problems
Protein turnover problems
Synapse Vulnerability
High demand for energy
Tell me about the transport problems faced by neurones. What diseases are implicated by this?
Transport problems: long distances, no homeostatic support en-route, slow (axonal transport disrupted in AD + HD)
Tell me about the protein turnover problems faced by neurones. What diseases are implicated by this?
Protein turnover problems: proteins deposits may overwhelm UPS; abnormal prns resistant to UPS (inadequate protein turnover implicated in AD/ HD/ PD)
Tell me about the synapse vulnerability of neurones. What diseases are implicated by this?
Synapse vulnerable: far away from soma and no obvious homeostatic support mechanisms along the axon which could detect misfolded proteins, limited homeostatic support, high energy consumer (synaptic dysfunction implicated in AD/ HD/ CJD)
Tell me about the problems of the high demand for energy of neurones and what diseases are implicated by this?
High demand for energy: prone to oxidative stress (oxidative stress associated with most neurodegenerative diseases)
Summary
- that neurones are polarised cells, and each region of the cell is engaged in a specific function
- neurones employ several mechanisms to degrade misfolded or damaged proteins
- retrograde signalling provides neurotrophic support and communicates injury messages
- neurones are vulnerable to axonal transport disruptions, accumulation of misfolded prns, synaptic dysfunction and oxidative stress.
