David chen 11307120002 STRESS ANR SERQTONIN SYSTEM
STRESS AND SEROTONIN SYSTEM David Chen 11307120002
WHAT IS SEROTONIN x Neurotransmitter(神经递质) x Also called5 hydrotrptamine(5HT)5羟色胺 x Synthesized from tryptophan
WHAT IS SEROTONIN? Neurotransmitter(神经递质) Also called 5-hydrotrptamine(5-HT)5-羟色胺 Synthesized from tryptphan
HOW ROES THIS SYSTEM ORK &Q (pre-v 501A 5-HT1B-R post-synaptic pre-synaptic MAOA neuron serotonin neuron degradation 5-HT1A-R ontogeny TPH1 VMAT2 H2-mediated 5-HT2C-R PET-1 i transport SERT synthesis→ 5-HT3A-R MAOA 5-HT1A-R SERT reuptake 5-HT2A-R 5-HT1A-R Fig from Genetic variation in cortico-arhygdala serotonin function and risk for stress- related disease
HOW DOES THIS SYSTEM WORK? Fig. from Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease
RISTRIBUTION OF SEROTONERGIC NEURONS IN OUR BRAIN mPFC mPFC内侧前额叶 DRN Amygdala杏仁体 DRN中缝背核 5-HT1A-R 5-HT1B-R amygdala 5-HT2A-R 5-HT2C-R M 5-HT3A-R Fig from Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease
DISTRIBUTION OF SEROTONERGIC NEURONS IN OUR BRAIN Fig. from Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease mPFC内侧前额叶 Amygdala杏仁体 DRN中缝背核
RELATION BETWEEN SEROTONIN AND STRESS x Exposure to stressors. serotonin neuron activity is increased Excerpted from Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus x...at all levels of the serotonin system.can influence. the response to stress x-Excerpted from Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease
RELATION BETWEEN SEROTONIN AND STRESS Exposure to stressors … serotonin neuron activity is increased… --Excerpted from Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus …at all levels of the serotonin system…can influence … the response to stress. --Excerpted from Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease
5-HT1B-R pre-synaptic MAOA neuron 5-HT1A-R TPH1 VMAT2 TPH2-mediated 5-HT2C-R ET- SERT 5-HT3A-R MAOA 5-HT1A-R SERT 5-HT2A-R 5-HT1A-R x Release x Synthesis x Vesicular packaging x Degradation x Receptor
Release Synthesis Vesicular packaging Degradation Receptor
5-HT1A-R x Autoreceptor(自受体) on the soma and dendrites of serotonin cells x-EXcerpted from Immunohistochemical evidence of the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei Whose activation inhibits DRN neuronal firing and consequent forebrain release Excerpted from Direct Immunohistochemical evidence of x the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei x Compromised by chronic stress leading to learned helplessness’(习得性无助) x-excerpted from Learned helplessness
5-HT1A-R Autoreceptor(自受体)on the soma and dendrites of serotonin cells --Excerpted from Immunohistochemical evidence of the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei Whose activation inhibits DRN neuronal firing and consequent forebrain release --Excerpted from Direct Immunohistochemical evidence of the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei. Compromised by chronic stress leading to ‘learned helplessness’（习得性无助） --excerpted from Learned helplessness
METHOD x Forced swim test x Evaluation of antidepressants(抗抑郁药)… aimed at rendering or preventing depressive-like states x-Excerpted from The mouse forced swim te x Tail suspension test 150 x Gene knockout luoxetine 0 5 10 (mg/kg)
METHOD Forced swim test Evaluation of antidepressants（抗抑郁药）… aimed at rendering or preventing depressive-like states --Excerpted from The mouse forced swim test. Tail suspension test Gene knockout
REFERENCE x [1]Sotelo C, Cholley B, El Mestikawy S, Gozlan H, Hamon M. Direct Immunohistochemical evidence of the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei. Eur Neurosci 1990; 2: 1144 1154 x[2 Seligman ME. Learned helplessness. Annu Rev Med 1972, 23: 407-412 x[3]C Adem et al. The Mouse Forced Swim Test J Vis Exp 2012 Jan 29: (59): e3638 x [4 Andrew Holmes Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease Neurosci Biobehav Rev. 2008 September; 32(7): 1293 1314.doi:10.1016/ i. neubiorev2008.03.006 x[5 Clifford EM, Gartside SE, Umbers V, Cowen PJ, Hajos M, Sharp T Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo. Br J Pharmacol 1998: 124: 206-212 x[6 Amat J, Baratta M, Paul E, Bland ST, Watkins LR, Maier SF Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat Neurosci 2005: 8: 365-371
REFERENCE [1] Sotelo C, Cholley B, El Mestikawy S, Gozlan H, Hamon M. Direct Immunohistochemical evidence of the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei. EurJ Neurosci 1990;2:1144– 1154. [2] Seligman ME. Learned helplessness. Annu Rev Med 1972;23:407–412 [3] C Adem et al. The Mouse Forced Swim Test J Vis Exp. 2012 Jan 29;(59):e3638 [4] Andrew Holmes Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease Neurosci Biobehav Rev. 2008 September ; 32(7): 1293– 1314. doi:10.1016/j.neubiorev.2008.03.006. [5] Clifford EM, Gartside SE, Umbers V, Cowen PJ, Hajos M, Sharp T. Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo. Br J Pharmacol 1998;124:206–212. [6] Amat J, Baratta MV, Paul E, Bland ST, Watkins LR, Maier SF. Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat Neurosci 2005;8:365–371
x Any suggestions will be highly appreciated
Any suggestions will be highly appreciated!