chp_15_sl_neurotox

Views:
 
     
 

Presentation Description

No description available.

Comments

Presentation Transcript

A Small Dose of ™ Neurotoxicity : 

A Small Dose of ™ Neurotoxicity An Introduction to Toxicology of the Nervous System

Introduction : 

Introduction “You cannot reach your full genetic potential with a damaged nervous system.” S.G. Gilbert

What is Neurotoxicity? : 

An adverse change in the chemistry, structure or function of the nervous system during development or at maturity, following exposure to a chemical or physical agent. What is Neurotoxicity?

Nervous System Sensitivity : 

Even minor changes in the structure or function of the nervous system may have profound consequences for neurological, behavioral, and related body functions. Nervous System Sensitivity

Ancient Awareness : 

Ancient Awareness “LEAD MAKES THE MIND GIVE WAY” Dioscorides - GREEK 2ND BC

Current Awareness : 

“The upsurge of interest in recent years in academia, industry, and government on the effects of toxic chemicals on the nervous system has created a new discipline of neurotoxicology.” Peter S. Spencer & Herbert H. Schaumberg, in Experimental and Clinical Neurotoxicology, 1980 Current Awareness

Historical Events : 

1930’s – Ginger-Jake Syndrome During prohibition, an alcohol beverage was contaminated with TOCP (triorthocresyl phosphate) causing paralysis in 5,000 with 20,000 to 100,000 affected. 1950’s – Mercury poisoning Methylmercury in fish cause death and sever nervous system damage in infants and adults. Historical Events

Case Studies : 

Case Studies Lead – damages developing brain Alcohol – Fetal alcohol syndrome MPTP – similar to Parkinson’s disease

Lead In Homes : 

Lead In Homes

Nervous Systems Effects : 

Nervous Systems Effects Developmental Neurotoxicity Reduced IQ Impaired learning and memory Life-long effects Lead Neurotoxicity

Alcohol (ethanol) : 

Alcohol (ethanol) C H H H OH Ethyl Alcohol C H H

Alcohol : 

Vulnerability of Developing Nervous System FAS – Fetal Alcohol Syndrome FAE – Fetal Alcohol Effects What is a save level of consumption during pregnancy? Alcohol

Effects of Prenatal Alcohol : 

Effects of Prenatal Alcohol

FAS Child : 

FAS Child

MPTP : 

MPTP 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine

MPTP Effects : 

1980s – Designer Drug Caused effects similar to Parkinson’s disease Damaged neurons that secrete dopamine MPTP Effects

Nervous System Biology : 

CNS – Central Nervous System PNS – Peripheral Nervous System Blood brain barrier Neuronal cells Neurotransmitters & receptors 10-100 billion cells with 1015 connections Nervous System Biology

Nervous System – CNS & PNS : 

Nervous System – CNS & PNS Central Nervous System (CNS) Brain & Spinal Cord Peripheral Nervous System (PNS) Afferent (sensory) Nerves – Carry sensory information to the CNS Efferent (motor) Nerves – Transmit information to muscles or glands

Nervous System : 

Nervous System Nervous System CNS Central Nervous System PNS Peripheral Nervous System Autonomic Somatic Sympathetic Parasympathetic

Central Nervous System : 

Central Nervous System Central Nervous System (CNS) (Brain and Spinal Cord) Peripheral Nervous System (PNS) Autonomic Somatic Sympathetic Parasympathetic Afferent (sensory) Nerves (Carry sensory information to the CNS) Efferent (motor) Nerves (Transmit information to muscles or glands)

Peripheral Nervous System : 

Peripheral Nervous System Peripheral Nervous System (PNS) Efferent (motor) Nerves – Transmit information to muscles or glands Somatic Nervous System Stimulates Skeletal muscles Autonomic Nervous System Stimulates Glands and Organs (e.g. heart) Sympathetic - Adrenergic – stress response Parasympathetic - Cholinergic – basic functions

Cells of the Nervous System : 

Cells of the Nervous System Neurons Information conductors Supporting Cells (Glia cells) Astrocytes (CNS – blood brain barrier) Oligodendrocytes (CNS – link cells) Schwann cells (PNS – wrap cells)

Blood-brain Barrier : 

Blood-brain Barrier Not an absolute barrier Caffeine (small) Methylmercury cysteine complex Lipids (brain is a ball of fat) Anatomic Characteristics Capillary endothelial cells are tightly joined – no pores between cells Capillaries in CNS surrounded by astrocytes Low protein concentration in CNS fluid Active ATP-dependent transporter – moves chemicals into the blood

Neuronal Cells : 

Neuronal Cells Axon Myelin (Schwann cell) Synapse Dendrite Cell Body Nucleus

Neurotransmission : 

Dopamine Transmitter Cell (Excitatory Neuron) Dopamine Receptor Cell (Post-synaptic receptor) Dopamine Receptor Synaptic Cleft Synaptic Vesicles Neurotransmission

Neuronal Transmission : 

Neuronal Transmission Inhibitory Synapse Excitatory Synapse +40 0 -40 -70 Action Potential IPSP EPSP Action Potential No Action Potential

Exposure Issues : 

Inhalation (e.g. solvents, nicotine) Ingestions (e.g. lead, alcohol) Skin (e.g. pesticides, nicotine) Physical (e.g. load noise) Exposure Issues

What causes neurotoxicity? : 

What causes neurotoxicity? Wide ranged of agents – chemical and physical

Types Of Neurotoxicity : 

Types Of Neurotoxicity Neuronopathy Cell Death. Irreversible – cells not replaced. MPTP, Trimethytin Axonopathy Degeneration of axon. Reversible. Hexane, Acrylamide Myelinopathy Damage to myelin (e.g. Schwann cells) Lead, Hexachlorophene Transmission Toxicity Disruption of neurotransmission Organophosphate pesticides, Cocaine, DDT

Neurotoxic Injury : 

Neurotoxic Injury Neuron Normal Neuronopathy Axonopathy Myelinopathy Transmission Axon Synapse Myelin

Examples of Neurotoxicology : 

Examples of Neurotoxicology Diseases Parkinson's, Alzheimer's, MS, ALS.. Environmental Lead, Methylmercury, PCBs Occupational Solvents, Pesticides Drugs - Clinical Vincristine, cisplatin Drugs - Social Alcohol, cocaine, nicotine

Neurotoxic Effects : 

Cognitive Effects - memory, learning, confusion Motor Effects - weakness, convulsion, paralysis Sensory Effects - vision, auditory, touch, balance Mood and Personality Effects - sleep, depression, irritability, excitability General Effects - loss of appetite, fatigue Neurotoxic Effects

Classification of neurotoxicants by mechanism of action : 

Classification of neurotoxicants by mechanism of action Temporary inhibition of nerve function Agents which alter membrane function Agents with interfere with synaptic transmission

Physiological Sensitivity : 

Dependence on oxygen Little anaerobic capacity CO – less available oxygen Cyanide – inability to use oxygen Dependence on glucose Sole energy source High metabolic rate Physiological Sensitivity

Physiological Sensitivity : 

Structure Long cell requires extensive intracellular transport Blood-Brain Barrier Developmental stage (lead and alcohol) Physiological Sensitivity

Reversibility of Damage : 

Neurons CANNOT divide and replace themselves Neurons CAN repair limited axonal damage Most Recovery Redundancy of Function Plasticity of Organization Reversibility of Damage

Classification of neurotoxicants by mechanism of action : 

Classification of neurotoxicants by mechanism of action Permanent inhibition of nerve function Agents which cause Anoxia Anoxic anoxia Ischemic anoxia Cytotoxic anoxia Agents which damage myelin formation Oligodendroglia (CNS) Schwann cells (PNS) Agents which damage peripheral axons Agents which damage nerve cell body Agents which cause localized CNS lesions

Neurological and Behavioral Effects of Exposure to Toxic Substances : 

Neurological and Behavioral Effects of Exposure to Toxic Substances Motor Effects - Convulsions, weakness, tremor, twitching, lack of coordination, unsteadiness, paralysis, reflex abnormalities, activity changes Sensory Effects - Equilibrium changes, vision disorders, pain disorders, tactile disorders, auditory disorders Cognitive Effects - Memory problems, confusion, speech impairment, learning impairment Mood and personality effects - Sleep disturbances, excitability, depression, irritability, restlessness, nervousness, tension, delirium, hallucinations General effects - Loss of appetite, depression of neuronal activity, narcosis stupor, fatigue, nerve damage

Normal Receptor-Ligand Interaction : 

Receptor Ligand Cell Membrane Signal Protein Positive Response Outside Cell Inside Cell Ligand binds to receptor 1 3 2 Normal Receptor-Ligand Interaction

Inactivation of Receptor by Toxicant : 

Toxicant 1 Toxicant inactivates receptor No Response 3 2 Inactivation of Receptor by Toxicant

Competition For Receptor : 

Toxicant 1 No Response 3 2 Ligand Toxicant out competes normal ligand Ligand cannot bind receptor Competition For Receptor

Who Is Vulnerable? : 

Who Is Vulnerable? Young or Old Male or Female Genetics - Individual Diff. Species

Vulnerability / Sensitivity : 

Fetal Nervous System Developing Nervous System Mature Nervous System Aging Nervous System Vulnerability / Sensitivity

Slide 44: 

A Small Dose of ™ Neurotoxicity

Additional Information : 

Additional Information Web Sites U.S. National Institute of Health - National Institute of Neurological Disorders and Stroke (NINDS). Online. Available HTTP: <http://www.ninds.nih.gov/> (accessed: 10 April 2003). Natural Resources Defense Council (NRDC). Online. Available HTTP: <http://www.nrdc.org/health/kids/cfqpa0599.asp> (accessed: 10 April 2003). NRDC site provides information on children’s health and neurotoxicology. Other Chapters Mercury, lead, pesticides

Authorship Information : 

Authorship Information For Additional Information Contact Steven G. Gilbert, PhD, DABT E-mail: smdose@asmalldoseof.org Web: www.asmalldoseof.org This presentation is supplement to “A Small Dose of Toxicology”

authorStream Live Help