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)