Central Nervous System Introduction Flashcards
(26 cards)
What structures comprise the CNS?
Brain
Upper spinal cord
How does neurotransmitters in teh CNS compare to the PNS?
Similar neurotransmitters are present, but CNS transmission is non-linear, involving complex networks and feedback loops
What makes CNS control more nuanced than PNS signalling?
Interneurons complete feedback loops, influencing multiple neurons at different points, making theraputic prediction more challenging
What roles do interneurons play in CNS transmission?
They create feedback loops, modifying signal transmission beyond simple linear pathways
Why is drug discovery for CNS disorders challenging?
1 - Complex neuronal interconnections -> Difficult to predict therapeutic outcomes
2 - Neurotransmitter adaptations -> Changes in synthesis and signalling can lead to tolerance, dependence, sisde effects
3 - Slow onset therapeutic effects -> Requires prolonged clinical management to determine the best treatment
What are the three categories of CNS signalling molecules?
1 - Fast neurotransmitters -> Glutamate, GABA, glycine (act on ligand-gated ion channels)
2 - Slow neurotransmitters -> Noradrenaline, dopamine (act on GPCRs)
3 - Neurotransmitters -> Neuropeptides, gaseous and lipid mediators, steroids (released by neurons, astrocytes, glial cells)
Which neurotransmitters can act as both fast and slow transmitters?
Serotonin and Acetylcholine
They interact with both ligan-gated ion channels and GPCRs
What major coniditons affect the CNS?
Neurodegenerative disease
Anxiety and sleep disorders
Depression
Schizophrenia
Epilepst
Pain disorders
How are anxiets disorders classified?
- Generalised anxiet disorder (GAD) -> Persistent anxiety without clear cause
- Panic disorder -> Sudden episodes of overwhelming fear
- Phobias -> Fear of specific objects or situations
- PTSD -> Trauma-induced anxiety symptoms
- OCD -> Ritualistic behaviours driven by anxiety
What is the link between anxiety and sleep disorders?
Anxiety can exacerbate insomnia, but sleep disorders can exist independently, affecting health and quality of life
What is GABA?
A fast inhibitory neurotransmitter, exclusive to the CNS, present in 30% of synapses
What is the relationship between GABA and glutamate?
GABA and glutamate share a metabolic pathway
Glutamine -> Glutamate (via glutaminase)
Glutamate -> GABA (Via glutamic acid decarboxylase GAD)
How is GABA signalling terminated?
Reuptake inot nerve terminals or surrounding glial cells, followed by recycling or metabolism
What are the main types of GABA receptors?
- GABAA (Ligan-gated ion channel) -> Fast inhibition via chloride influx (hyperpolarisation)
- GABAB (GPCRs, mianly pre-synaptic) -> Inhibit voltage-gated calcium channels, reducing neurotransmitter release
How do bensodiazepines modulate GABAA receptors?
They bind allosterically at teh alpha-gamma subunit interface, increasing GABA affinity and chloride channel opening frequency
How do barbiturates differ from benzodiazepines?
Barbiturates directly open the chloride channel, leading to stronger inhibition and higher overdose risk
What are clinical uses of GABAA receptor modulators?
Benzodiazepines (Diazepam, Temazepam) -> Anxiety, insomnia, anticonvulsant
Barbiturates (Zopiclone) -> Seizures, sedation
Flumazenil -> Benzodiazepine, overdonse antidote
What is the monoamine theory of depression?
Depression rsults from a functional deficit of monoamine neurotransmitters (noradrenaline and serotonin), while mania results from a functional excess
Whay is depression treatment challenging?
Varied symptoms (low mood, motivation loss, insomnia)
Complex neurochemical networks affect therapeutic success
Difficult to model depression in animals
Therapeutic lag (weeks to months for drug effects)
How do antidepressents enchance monamine signalling?
- Inhibit reuptake -> Prolong monoamine presence in synaptic cleft
- Inhibit degradation -> Prevent monoamine breakdown, increasinf recycling and re-release
What are the three major classes of antidepressants?
- Tricyclic Antidepressants (TCAs) -> Block noradrenaline and serotonin reuptale (high side effect profile)
- Selective Serotonin Reuptake Inhibitors (SSRIs) -> Fluoxetine (Prozac), more tolerable, first-line treatment
- Monoamine Oxidase Inhibitors (MAO-0s) -> Inhibit monoamine breakdown; risk of drug interactions
Why are TCAs no longer first-line treatment?
High side effect profile (anticholinergic effects, cariotoxicity, risk in suicidal patients). Now mainly used for neuropathic pain treatment
What is the advantage of SSRIs?
More specific for serotonin, better rolerated, lower toxicity than TCAs
What other pathways cotnribute to depression?
Hypothalamic-pituitary-adrenal axis (HPA) -> Chronic stess activation
Excitotoxic glutamate action (NMDA receptors) -> Promotes neural apoptosis
Brain-derived neurotrophic factor (BDNF) -> Neuroprotective, enhances neurogenesis
