M7 - Neuroscience Flashcards
Farmakologiske migræne triggers
- Histamine
- GTN (glyceryltrinitrate)
- CGRP
c-fos
Udtryk af c-fos er en indirekte markør for neuronal aktivering da den ofte er udtrykt I neuronerne efter aktionspotentialer.
• Et forøget udtryk af c-fos indikerer at neuronerne for nylig har været aktive
Migræne Endpoints:
- Forandring i udtryk af c-fos og andre markører for neuronal aktivering i TNC (Trigeminal Nucleus Caudalis), TG og dura mater
- Adfærds undersøgelser
Afdærdsundersøgelse ifm hovedpine i rotter?
- Hovedpine
- Fotofobi
- Fonofobi
- Kvalme
- Bevægelighed?
- Normal adfærd?
Schizophrenia
- kompleks af mange sygdomme
- onset sidste i teenage årene
- ratio: mand>kvinder
Symptomer for Schizo
- Positive (hallucinations, obsession, disorganised speech and thinking)
- Negative (lack of self-care, asocial, decreased motivation)
- Cognitive deficits (The ability to keep recently learned information in mind and use it right away, bad memory)
=> samlet = schizophrenia
ASSAYS TESTS: Schizophrenia.
Mechanistic assays => can be performed in naïve animals
- Induced hyperactivity tests
a) Amphetamine b) Cocaine induced - Isoniazide Antagonism (Isoniazide induced convulsions)
Induced hyperactivity tests
Typical antipsychotics:
Block receptors in the brain’s dopamine pathways (dopamine
antagonist)
a) Amphetamine Induced hyperactivity
(increases concentration of dopamine, seritonine and noradrenaline (norepinephrine)
b) Cocaine Induced hyperactivity
(increases concentration of dopamine, seritonine and noradrenaline (norepinephrine)
Exampels of rodent disease models of schizophrenia
negative og conginitive
Genetic
- e.g. GLAST knockout mice
- e.g. DISC1 knockout mice
Non-pharmacological
- e.g. Isolation rearing
- e.g. Lesion models
Pharmacological
- e.g. Phencyclidine (PCP)- models
PCP disease-models (schizo)
PCP (Phencyclidine) is a non-competitive N-Methyl-D-aspartic acid (NMDA) receptor antagonist
Administration of PCP and PCP-like compounds results in NMDA receptor hypo-function (NRhypo)
PCP virkning
Administration of PCP and PCP-like compounds has been shown to induce schizophrenic-like symptoms in healthy humans as well as in rodents, and to exacerbate symptoms in schizophrenic patients.
Schizo
Assessing negative symptoms: models
Social Interaction Test (social behaviour)
Nest Building Test
self-neglect, social withdrawal, lack of goal-directed behaviour, Unawareness of the surroundings
Assays normaly used for assessing symptoms of depression
- Sucrose Preference Test
- Tail suspension
- Porsolt forced swimming test
- Light / dark (anxiety)
- Marble burrying (anxiety)
- Open Field
Assessing cognitive deficits
Cognitive deficits:
Attentional set shifting (Wisconsin Card Sorting Test - ændring af regler undervejs)
Reversal Learning (attention / learning memory - ‘tryk på edderkoppen’ -> ændres til tryk på flyet)
Morris Water Maze
(learning memory / spartial memoty)
Årsager til Major Depressive Disorder (MDD)
- Stressful events during childhood
- Chemical changes in the brain
- Genes (one parent with depression increases risk X3) -Triggered by stressful events (HPA-axis)
Factors that increases risk of developing MDD
- High risk after thrombosis in the brain
- Increased risk if you live alone
- If you are alcoholic
- Use of amphetamine and/ or epecially ecstasy
- Increased risk with age
Patogenesen MDD
Depression is due to a state of deprivation in the synapses of one or more neurotransmitters (serotonin, noradrenalin)
Treatment of MDD
1)Psychotherapy
2) Pharmacological
- Tricyclic antidepressants (TCA’s)
- Selective serotonin reuptake inhibitors (SSRI’s)
- Norepinephrine-Selective Reuptake Inhibitors (NSRI’s)
- Monoamine oxidase inhibitors (MAOI’s)
3) Electrotherapy
- Electroconvulsive therapy (ECT)
genetiske rotte sygdomsmodeller for MDD
- Glucocorticoid receptor transgenic mice (HPA-system)
- Dopamine (DAT) transporter knockout mice
farmakologiske rotte sygdomsmodeller for MDD
Withdrawal from chronic psychostimulants (amphetamine, cocaine i.e.)
Non-farmakologiske rotte sygdomsmodeller for MDD
- Pre-natal stress (cage in angle, elevated, restraint)
- Chronic mild stress (CMS)
Alzheimers sygdom
- Akkumulation af beta-amyloid plaques ekstracellulært
- Intracellulære neurofibrillary tangles (”sammenfiltringer”)
- Granulovakuolær degeneration i hippocampus
demens versus alzheimers
- Demens er et symptombillede (svækkelse som sker i løbet af livet)
- Alzheimers er den hyppigste årsag til at få demens (presenil demens)
Symptomer på Alzheimers
- svækket hukommelse, der hurtigt forværres
- skriger højt uden nogen indlysende grund
- har svært ved at læse og skrive
- desorientering og forvirring
- svært ved at forstå nemme spørgsmål
Patogenese Alzherimers
o mutationer i APP + enzymer
o aldrig mutationer i Tau-genet
o Beta-amyloid fører til tanglets
o Tanglets styrer sygdomsudviklingen
Patogenese for dyremodeller Alzherimers
o mutationer i APP + enzymer
o mutationer i tau-genet (modsat msk)
o MEN beta-amyloid fører IKKE til tanglets (modsat msk)
Parkinson’s disease
IKKE noget man dør af, men noget man dør med!
De fleste får det omkring 65 års alderen.
Dopamin nedsættende
Symptomer på Parkinson’s
- hypokinesis
- tremor (ryster)
- rigiditis
- bending the trunk forward
- mest psykologisk i det også -> hjernen skal overbevises om at den kan noget
Man bliver også deprimeret og aldrig rigtig glad eller rigtig ked af det, stresset osv. (alt hvad Dopamin normalt stimulerer!)
Patogenese Parkinson’s
- man mister de Dopamin producerende celler/neuroner. → giver rystelser og ikke en kontinuerlig motorisk bevægelse
- Alpha-synuclein (protein i hjernen) intraneural inclusions aggregated to form Lewy bodies
- Man mister også Adrenalin producerende celler!
Behandling mod Parkinson’s
- Farmakologi:
o Levodopa (L-DOPA)
o Dopamin agonists - Surgical
o Deep brain stimulation (sætter en elektrode ind i hjernen som giver et elektrisk stimuli–> dopamin produktionen stimuleres)
o Implantation of cells
