NEU 365T Lecture Notes - Lecture 13: Adenylyl Cyclase, Neurotrophic Factors, Protein Kinase
Document Summary
Acute antidepressant increase ne postsynaptic receptor activation (g s -coupled) elevates camp. Ar (mechanism for depression) down-regulation vs antagonist (rapid effect) to treat camp is still elevated with chronic treatment vs w/o even after down-regulation (hence the time-lag for therapeutic effects) Goal look for rapidly acting anti-depressants. Ex: neurotransmitters, neurohormones (i. e. crf), neurotrophic factors, drugs. Alters gene expression (transcription of dna to mrna) Long-term adaptive changes in neuronal function and structure. Ex: synaptic efficacy, atrophy, growth of neurons, etc. Why prozac therapeutic effects has a time lag. Repeated antidepressant treatment chronic activation of second messenger cascades. Ex: adenylyl cyclase camp pka. Activate transcription factors (substrates of 2nd messenger-dependent protein kinases) Get in nucleus - bind to dna affect transcription of downstream. Phosphorylation of tfs alter their transcriptional activity. Ex: creb (camp response element-binding protein = transcription factor) & its activation of pka (in cytosol then transported into the nucleus)
