8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework** Consortium leader PETER PAZMANY CATHOLIC UNIVERSITY Consortium members SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund *** **Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben ***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg. PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY sote_logo.jpg dk_fejlec.gif INFOBLOKK 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology BASICS OF NEUROBIOLOGY NEUROTRANSMITTERS I. www.itk.ppke.hu Neurobiológia alapjai (Neurotranszmitterek I.) ZSOLT LIPOSITS Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu DEFINITION AND CRITERIA OF NEUROTRANSMITTERS NEUROTRANSMITTERS ARE ENDOGENOUS BIOACTIVE SUBSTANCES SYNTHESIZED BY NEURONS. THEY ARE RELEASED FROM THE CELLS, ACT VIA SPECIFIC RECEPTORS COUPLED TO THE MEMBRANE OF POSTSYNAPTIC TARGET STRUCTURES AND MODIFY THE ELECTRIC AND METABOLIC CONDITIONS OF THE AFFECTED CELLS. CRITERIA OF CHEMICAL NEUROTRANSMITTERS: 1. THE SYNTHESIS OF THE CHEMICAL TRANSMITTER TAKES PLACE IN THE PRESYNAPTIC NEURON 2.THE SYNTHESIZED TRANSMITTER OR IT PRECURSOR IS STORED IN THE RELEASE COMPARTMENT OF THE CELL, MOST FREQUENTLY IN AXON TERMINALS 3.RELEASE OF THE NEUROTRANSMITTER INTO THE SYNAPTIC CLEFT UPON EXCITATION OF THE PRESYNAPTIC ELEMENT 4.BINDING OF THE TRANSMITTER TO ITS RECEPTOR/S/ THAT BELONG TO IONOTROPIC AND METABOTROPIC CLASSES 5.TERMINATION OF THE ACTION OF TRANSMITTERS AND ITS TRIGGERED MECHANISMS Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 www.itk.ppke.hu CLASSIFICATION OF NEUROTRANSMITTERS THE NEUROTRANSMITTERS BELONG TO TWO MAIN CATEGORIES, THE CLASSICAMINE TYPE AND THE NON-CLASSIC PEPTIDE TYPE GROUPS COMPARISON OF THE PRODUCTION OF CLASSIC AND NON-CLASSIC TRANSMITTERS TYPE CELL BODY AXON TERMINAL EXAMPLE AMINE PRODUCTIONOF 1. SYNTHESIZING ENZYMES 2. STORAGE VESICLES AXONAL TRANSPORT OF 1. SYNTHESIZING ENZYMES 2. STORAGE VESICLES SUPPLYOF CONSTITUENTS: 1. FROM CELL BODY 2. LOCAL SYNTHESIS 3. RE-UPTAKE ACETYLCHOLINE GABA GLUTAMATE SEROTONIN NORADRENALINE PEPTIDE 2. CO PRODUCTIONOF 1. PEPTIDE PRECURSORS NVERTING ENZYMES 3. STORAGE VESICLES AXONAL TRANSPORT OF STORAGE VESICLES SUPPLY OF CONSTITUENTS FROM CELL BODY ENKEPHALIN DYNORPHIN SUBSTANCE P VASOPRESSIN SOMATOSTATIN CHOLECYSTOKININ Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu ATTRIBUTES DESCRIPTION NAME DOPAMINE CHEMICAL NAME, STRUCTURE 4-(2-AMINOETHYL)BENZENE-1,2-DIOL SYNTHESIS DERIVATIVE OF: L-DOPA SYNTHESIZING ENZYMES: TYROSINE HYDROXYLASE(TH), DOPA DECARBOXYLASE REGULATION TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL OF SYNTHESIZING ENZYMES STORAGE CELLULAR STRUCTURESYNAPTIC VESICLE TRANSPORTER VESICULAR MONOAMINE TRANSPORTER-2 (VMAT-2) RELEASE BY EXOCYTOSIS,PRESYNAPTIC REGULATION VIA AUTORECEPTORS (D2 FAMILY) INACTIVATION BY MONOAMINE OXYDASE (MAO), CATECHOL-O-METHYL TRANSFERASE (COMT), DOPAMINE TRANSPORTER (DAT) RECEPTORS D1-LIKE FAMILY: D1 AND D5 RECEPTORS, G PROTEIN-COUPLED D2-LIKE FAMILY: D2, D3 AND D4 RECEPTORS , G PROTEIN-COUPLED EXPRESSION IN BRAIN INNUCLEI OF THE BRAIN STEM AND HYPOTHALAMUS, MESOLIMBIC, MESOCORTICAL, NIGROSTRIATAL, TUBEROINFUNDIBULAR DOPAMINERGIC SYSTEMS SIGNIFICANCE COGNITION, ATTENTION,MEMORY, PROBLEMSOLVING, REWARD, MOOD, PROLACTIN SECRETION, PARKINSON DISEASE, SCHIZOPHRENIA, AGING Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu DOPAMINERGIC NEURONS IN THE HYPOTHALAMUS DOUBLE IMMUNOCYTOCHEMICAL LABELING REVEALS BLACK, DOPAMINERGIC NEURONS CONTACTING BROWN, CORTICOTROPIN-RELEASING HORMONE-SYNTHE- SIZING NEURONS IN THE PARAVENTRICULAR NUCLEUS Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu ATTRIBUTES DESCRIPTION NAME NOREPINEPHRINE (NORADRENALINE,NE) CHEMICAL NAME, STRUCTURE 4-[(1R)-2-AMINO-1-HYDROXYETHYL]BENZENE-1,2-DIOL SYNTHESIS DERIVATIVE OF: DOPAMINE SYNTHESIZING ENZYME DOPAMINE BETA-HYDROXYLASE REGULATION TRANS-SYNAPTIC INDUCTION, GLUCOCORTICOIDS STORAGE CELLULAR STRUCTURESYNAPTIC VESICLE TRANSPORTER VESICULAR MONOAMINE TRANSPORTER-2 (VMAT-2) RELEASE BY EXOCYTOSIS,PRESYNAPTIC REGULATION VIA AUTORECEPTORS (ALPHA-2) INACTIVATION BY MONOAMINE OXYDASE (MAO) , RE-UPTAKEBY NOREPINEPHRINE TRANSPORTER (NET) RECEPTORS G PROTEIN-COUPLED RECEPTORS, ALPHA AND BETA TYPES IN THE BAIN: ALPHA 2 INHIBITS ADENYLYL CYCLASE, BETA 1 ACTIVATESIT EXPRESSION IN BRAIN CELL GROUPS IN THE CAUDAL PART OF THE BRAINSTEM SIGNIFICANCE ATTENTION, AROUSAL, STRESS, FEEDING REGULATION, ANTI DEPRESSION DRUG DEVELOPMENT Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 www.itk.ppke.hu DISTRIBUTION OF CATECHOLAMINERGICCELL GROUPS IN THE RODENT BRAIN Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 www.itk.ppke.hu ATTRIBUTES DESCRIPTION NAME SEROTONIN CHEMICAL NAME, STRUCTURE 5-HYDROXYTRIPTAMINE(5-HT) SYNTHESIS DERIVATIVE OF: TRYPTOPHAN SYNTHESIZING ENZYMES: TRYPTOPHAN HYDROXYLASE (TPH), AROMATIC L-AMINO ACID DECARBOXYLASE REGULATION PRECURSOR CONCENTRATION,PHOSPHORYLATION OF TPH STORAGE CELLULAR STRUCTURESYNAPTIC VESICLE TRANSPORTER VESICULAR MONOAMINE TRANSPORTER-2 (VMAT-2) RELEASE BY EXOCYTOSIS,PRESYNAPTIC REGULATION VIA AUTORECEPTORS (5-HT1A) INACTIVATION BY MONOAMINE OXYDASE (MAO) , RE-UPTAKEBY SEROTONIN TRANSPORTER RECEPTORS LIGAND-GATED ION CHANNEL (5-HT3), G PROTEIN-COUPLED RECEPTORS (5-HT1-2, 5-HT3-7) EXPRESSION IN BRAIN RAPHE NUCLEI OF THE BRAINSTEM SIGNIFICANCE AGGRESSION, OBSESSIVE-COMPULSIVE BEHAVIOR, FEEDING REGULATION, OBESITY, ANTI DEPRESSION DRUG DEVELOPMENT (SSRI) Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu ATTRIBUTES DESCRIPTION NAME ACETYLCHOLINE (ACh) CHEMICAL NAME, STRUCTURE 2-ACETOXY-N,N,N-TRIMETHYLETHANAMINIUM SYNTHESIS DERIVATIVE OF: ESTER OF ACETIC ACID AND CHOLINE SYNTHESIZING ENZYME CHOLINE ACETYLTRANSFERASE REGULATION ACTIVITY, ALLOSTERIC INHIBITION, PRECURSOR AVAILABILITY STORAGE CELLULAR STRUCTURESYNAPTIC VESICLE TRANSPORTER VESICULAR AChTRANSPORTER RELEASE BY EXOCYTOSIS,MINIATURE END-PLATE POTENTIALS, QUANTAL RELEASE INACTIVATION ACETYLCHOLINESTERASE, CHOLINE TRANSPORTER RECEPTORS NICOTINIC, IONOTROP, LIGAND-GATED ION CHANNEL, EXCITATORY MUSCARINIC, G PROTEIN-COUPLED, M1-M4 EXPRESSION IN BRAIN BASALFOREBRAIN, HABENULA, BRAIN STEM SIGNIFICANCE LEARNING,MEMORY, ATTENTION, AGING, ALZHEIMER DISEASE Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 www.itk.ppke.hu ATTRIBUTES DESCRIPTION NAME GLUTAMATE CHEMICAL NAME, STRUCTURE GLUTAMIC ACID SYNTHESIS DERIVATIVE OF: ALPHA-KETOGLUTARATE AND GLUTAMINE SYNTHESIZING ENZYMES AMINOTRANSFERASE, GLUTAMINASE REGULATION THEGLUTAMINE-GLUTAMATE CYCLE (GLIA-NEURON) STORAGE CELLULAR STRUCTURESYNAPTIC VESICLE TRANSPORTER VESICULAR GLUTAMATE TRANSPORTER (VGLUT1-3) RELEASE BY EXOCYTOSIS,PRESYNAPTIC REGULATION VIA AUTORECEPTORS (mGLuR2, mGLuR3) INACTIVATION NEURONALAND GLIAL UPTAKE BY PLASMA MEMBRANE GLUTAMATE TRANSPORTERS RECEPTORS IONOTROPIC, AMPA (GluR1-4), KAINATE (GluR5-7, KA1-2), NMDA (NR1, NR2A-2D) METABOTROPIC, G PROTEIN-COUPLED (mGluR1-7) EXPRESSION IN BRAIN THROUGHOUT THE BRAIN SIGNIFICANCE LEARNING,PLASTICITY, LONG TERM POTENTIATION, NEUROTOXICITY Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 www.itk.ppke.hu ATTRIBUTES DESCRIPTION NAME HISTAMINE CHEMICAL NAME, STRUCTURE 2-(1H-IMIDAZOL-4-YL)ETHANAMINE SYNTHESIS DERIVATIVE OF: HISTIDINE SYNTHESIZING ENZYMES L-HISTIDINE DECARBOXYLASE REGULATION PRECURSOR AVAILABILITY STORAGE CELLULAR STRUCTURESYNAPTIC VESICLE TRANSPORTER VESICULAR MONOAMINE TRANSPORTER-2 (VMAT-2) RELEASE BY EXOCYTOSIS, AUTORECEPTORS INACTIVATION HISTAMINE-N-METHYL TRANSFERASE, MAO-B RECEPTORS HISTAMINE RECEPTORS 1-4 EXPRESSION IN BRAIN TUBERO-MAMMILLARY NUCLEI OF THE CAUDAL HYPOTHALAMUS (E1-5) SIGNIFICANCE SLEEP-WAKING CYCLE, PSYCHOMOTOR PERFORMANCE Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 www.itk.ppke.hu ATTRIBUTES DESCRIPTION NAME GABA CHEMICAL NAME, STRUCTURE GAMMA -AMINOBUTYRIC ACID SYNTHESIS DERIVATIVE OF: L-GLUTAMATE SYNTHESIZING ENZYMES GLUTAMATE DECARBOXYLASE (GAD) REGULATION ENDPRODUCT STORAGE CELLULAR STRUCTURESYNAPTIC VESICLE TRANSPORTER VESICULAR GABA TRANSPORTER (VGAT) RELEASE BY EXOCYTOSIS, PRESYNAPTIC INHIBITION INACTIVATION GABAAMINOTRASNFERASE RECEPTORS GABA A, CHLORIDE CHANNEL, WITH VARIOUS BINDING SITES (GABA, PICROTOXIN, BARBITURATE, BENZODIAZEPINE, STEROID) GABAB EXPRESSION IN BRAIN DIFFUSELYDISTRIBUTED CELL GROUPS IN THE ENTIRE NEUROAXIS SIGNIFICANCE GENERAL INHIBITION AND COUNTERBALANCING OF EXCITATORYACTIONS, ROLE IN EPILEPSY, ANXIETY AND CONVULSION Basics of Neurobiology: Neurotransmitters I. 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 14 www.itk.ppke.hu ATTRIBUTES DESCRIPTION NAME GLYCINE CHEMICAL NAME, STRUCTURE AMINOETHANOIC ACID SYNTHESIS DERIVATIVE OF: SERINE SYNTHESIZING ENZYMES SERINE HYDROXYMETHYLTRANSFERASE REGULATION ENDPRODUCT STORAGE CELLULAR STRUCTURESYNAPTIC VESICLE TRANSPORTER NOT KNOWN RELEASE BY EXOCYTOSIS INACTIVATION CONVERTED TO GLUTATHIONE, GLYCINETRANSPORTERS RECEPTORS CHLORIDE CHANNEL EXPRESSION IN BRAIN MOST STUDIES IN THE SPINAL CORD, BRAIN IS A RISING FIELD SIGNIFICANCE GENERAL INHIBITION AND COUNTERBALANCING OF EXCITATORYACTIONS