Spring 2018: RXRS 409: Neuroimmunology: Focus on Disease and Therapy

USC School of Pharmacy

Spring 2018: RXRS 409: Neuroimmunology: Focus on disease and therapy

Coordinator/Instructor:Liana Asatryan, PhD

Research Assistant Professor,

Department of Clinical Pharmacy

University of Southern California

(323)442-1495

MCA-9121

Course Weight:4 Units

Days/Time/Location:M/W/ 3:30-4:50pm/ THH215

Final Exam Date: TBD

Introduction

Neuroimmunology is an evolving interdisciplinary field that combines neuroscience, immunology, molecular and cell biology as well as neuropharmacology in an attempt to better understand the role of the interaction of immune and nervous systems in health and development of diseases. Building evidence suggests that immune responses to environmental and genetic challenges play an essential role in the development of many central nervous system (CNS) pathologies including ischemic stroke, demyelination, degeneration, infections and trauma, drug addiction. This course will cover topics on the role of the immune system in maintaining a healthy brain and the consequences of improper immunological challenges in the development of the CNS disorders. Topics to be presented over the course of the semester include: history of neuroimmunology, cellular and molecular bases of the nervous and immune system, communication between the nervous and immune system, the role of the immune system as it relates to the brain function during neurological disorders, nervous system regulation of the immune responses. The course will be focusing on the existing approaches as well as the new diagnostic and therapeutic strategies for the treatment of the CNS disorders. In addition, the challenges related to the development of therapeutics for the treatment of the CNS disorders will be presented.

Objectives

This lecture course is designed for upper-level undergraduate and early graduate students and should have broad appeal to many USC students including Pre-Pharmacy, Pre-Medicine and other health and life science majors as well as early stage Master students in health or biological sciences.

Upon successful completion of this course, students should be able to demonstrate a
working knowledge of:

The history, development and overall framework of the field of Neuroimmunology.
The cellular and molecular components of the nervous and immune systems.
The players and basic mechanisms involved in the interactions between the nervous and immune system.
The importance of neurogilal cells in regards to maintaining a healthy brain and the role in neuroinflammation.
The role of inflammatory mediators including cytokines, chemokines and molecules of the complement system and their role in the neuroimmune response.
How environmental insults (for example; infections, drugs, alcohol) and/or genetic factors can lead to an altered immune response and participate in the development of neurological diseases.
The neuroimmune bases of diverse neurological disorders ranging from ischemic stroke to neurodegeneration, CNS infections and drug abuse.
The existing and evolving experimental and pharmacological therapeutic strategies targeting neuroimmune mechanisms to treat neurological disorders.

Assignments and Grading:

Class participation: 10 pts (5%)

5 quizzes @ 10 pts each 50 pts (25%)

2 midterm exams @ 40 pts each: 80 pts (40%)

1 final exam (partially cumulative) 60 pts (30%)

Total: 200 pts (100%)

Attendance at all classes is expected and may be considered when assigning final grades.

Participation will include asking and answering questions and being actively involved in the discussion. It is expected that the students read the assigned papers prior to the lecture and be prepared to discuss background, current understanding, treatments, and gaps in knowledge for the topic in each lecture.

There will be 5 quizzes, two mid-term examinations and one final examination for this course. The questions for quizzes and exams will primarily be based on the lecture content and text books. The midterms and the final exam will include multiple choice questions T/F questions fill-in the blank questions (all 2 points each), and 1 short essay (10 points).

There are no make-up exams. If exceptional circumstances prevent you from attending an exam, your reason for missing it must be accompanied by a written statement from a third party (e.g. a note from a medical doctor).

Notes, books, calculators, electronic dictionaries, regular dictionaries, cell phones or any other aids are not allowed during exams.

Students will be asked to complete an anonymous critical evaluation of the course at its completion.

Course Readings

Reading materials will be supplemented with a variety of source materials including articles from scientific journals and public websites. Most of the material will be posted on Blackboard http://blackboard.usc.edu/.

Required Reading

Neuroimmune Pharmacology

Howard E. Gendelman , Tsuneya Ikezu; ISBN: 978-0-387-72572-7 (Print) 978-0-387-72573-4 (Online) The chapters of this book will be posted on Blackboard.

Recommended Readings

Neuroimmunity: A New Science that Will Revolutionize how We Keep Our Brains Healthy and Young

Michal Schwartz, Anat London, Olle Lindvall; ISBN: 978-0-300-20347-9

Neural-Immune Interactions in Brain Function and Alcohol Related Disorders

Changhai Cui, Lindsay Grandison and Antonio Noronha; ISBN:978-1-4614-4728-3

Chapters from this book will be available on Blackboard.

The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, and Our Overall Health. Emeran Mayer; ISBN-10: 0062376551

Co-Requisite/Concurrent Enrollment: NA

Course Pre-requisites

Students should have completed 2 years of undergraduate biology (BISC 220/221, etc). Courses in Neuroscience (NEUR421) or Immunology (450L) are preferred.

Course Outline

Week & Date / Topic / Subtopics to be Included / Assigned and Supplemental Reading
Introduction and Background
Week 1
Aug. 20, 22 /

Introducing Neuroimmunology as an evolving discipline

2. Overview of the nervous system / Basic principles of nervous and immune systems. Merging of two disciplines; historical development of the field. Why is it important in the context of understanding diseases of the nervous system?
Structure, function of the nervous system with the focus on the central nervous system (CNS), brain barriers. / Schwartz/London Chapter 1;
Gendelman/Ikezu, Chapter 7
Week 2
Aug. 27, 29 /

Overview of the immune system

Function of the immune system

Quiz 1 / Cellular basis of the immune system; innate and adaptive immunity, cells of the immune system.
Normal immune responses – inflammation, acute, chronic. Myeloid cells – phagocytosis.
Review of the quiz and discussion / Gendelman/Ikezu, Chapters 1,11,12,14
Week 3
Sept.
5 /

Introduction to neuroinflammation

/ Acute, chronic neuroinflammation; neurogenic neuroinflammation. The neuroinflammatory basis of disease of the nervous system. / Gendelman/Ikezu, Chapters 13
Articles will be available on Blackboard
Week 4
Sept. 10, 12 / 1. Molecular basis of neuroinflammation / Glial and neuronal signaling: cytokines, chemokines, complement factors; pattern recognition receptors, inflammasomes; role in normal brain function and neuroinflammation. / Gendelman/Ikezu, Chapters 8,13,16,17
Week 5
Sept. 17, 19 / 1. Neuroinflammation - main players / Cells of the brain immune system – microglia, astrocytes, oligodendrocytes, functions, interactions with neuronal cells. / Gendelman/Ikezu, Chapters 10,13
Week 6
Sept. 24, 26 / Quiz 2
1. Nervous and immune system interactions

Review of recent topics

/ Review of the quiz and discussion
Brain-immune interactions; how does immune system affect the brain functions? How does brain regulate the adaptive and innate immunity? Hypothalamic-pituitary-adrenal axis. CNS portals, blood brain barrier, brain as an immune active organ.
In class discussion with active engagement of students. / Schwartz/London Chapter 1
Gendelman/Ikezu, Chapters 2,3,12
Inflammatory Diseases of the Nervous System
Week 7
Oct.
1, 3 /

Exam

2. Ischemia-reperfusion, stroke
Dr. Camelia Danilov* / 1st Midterm (In class)
Neuroimmune mechanisms of ischemic brain injury. Understanding specific inflammatory mediators and anti-inflammatory response to resolve inflammation and repair. Therapeutic approaches to the treatment of stroke. / Book chapters and articles will be available on Blackboard
Week 8
Oct. 8, 10 / 1,2. Autoimmunity and demyelinating disorders / Mechanisms of autoimmunity. Demyelinating disorders - focus on multiple sclerosis (MS). Neuroimmune crosstalk during MS, repair. Therapeutic approaches. / Gendelman/Ikezu, Chapters 23,24,26,43
Quiz 3
1,2. Neurodevelopmental disorders / Review of the quiz and discussion
Neuroimmune interactions during Autism Spectrum Disorders. Maternal immune factors, environmental neuroinflammatory factors in pathogenesis of the disease. Pathophysiology of mood and anxiety disorders. Potential therapeutic targets. / Gendelman/Ikezu, Chapters 39,40
Week 9
Oct. 15, 17 / 1,2. Disorders of the nervous system caused by infections and trauma / Role of immune system in neuropathology during viral (HIV, etc) and bacterial (meningitis) infections of the brain. Traumatic challenge of the brain and inflammation. / Gendelman/Ikezu, Chapters 27,28,29,38,44
Week 10
Oct. 22, 24 / 1,2. Neurodegenerative disorders – Alzheimer’s disease; Parkinson’s Disease / Pathophysiology of neurodegenerative disorders with the emphasis on neuroimmune component. Focus on Alzheimer’s, Parkinson’s diseases. Existing therapeutic approaches. / Gendelman/Ikezu, Chapters 22,30,31,42,45,46
Week 11
Oct. 29, 31 / 1. Review of recent topics
Quiz 4
2. Exam / In class discussion with active engagement of students.
Review of the quiz and discussion
2nd Midterm (In class)
Week 12
Nov.
5, 7 /

Drug- and alcohol-use brain disorders

Gut-brain interactions

Rachel Reyes* / Neural-immune interactions during alcohol and drug abuse; brain function and behavioral consequences. Fetal alcohol syndrome.
Gut microbiome, its role in regulation of stress and neuroinflammation, role in pathophysiology of CNS disorders. Enteric nervous system, brain – gut interaction. Targeting microbiome for treatment of neurological diseases. / Gendelman/Ikezu, Chapter 41;
Cui/Grandison/Noronha
Chapters 8,10,11,18
Book chapters and articles will be available on Blackboard
Existing Therapies and New Directions
Week 13
Nov. 12, 14 / 1,2. Neuroinflammation as a therapeutic target in the CNS disorders / Approaches targeting neuroimmune mechanisms for treatment of neurological disorders. Anti-inflammatories, immunomodulators. Immunotherapies and future drug development strategies. / Gendelman/Ikezu, Chapters 45,46,54,55,56
Week 14
Nov. 19 / Quiz 5
1,2. Therapeutics of the CNS disorders / Review of the quiz and discussion
Summarizing existing therapies for the neurological disease covered earlier, i.e. stroke, MS, neurodegenerative disorders, CSN infections, trauma, drug- and alcohol-abuse. / Gendelman/Ikezu, Chapter 42;
Cui/Grandison/Noronha
Chapter 17
Week 15
Nov. 26, 28 /

Neuroimaging and novel drug development for the CNS disorders

Review of recent topics

/ New directions in diagnostics and target identification of neurological disease, use of neuroimaging techniques. Drug development challenges for CNS disorders.
Preparation for the Final Exam / Gendelman/Ikezu, Chapters 49,50,53
Final Exam – After Dec. 5

* - Invited speakers

Catalogue description:

Newly evolving science focusing on the role of neuroimmune communication in the pathophysiology of the CNS disorders. Neuroinflammation as a target for novel therapeutic approaches.