Vichaya, Elisabeth Good (2011-05). The Impact of Social Stress on Central Nervous System Inflammation and T Cell Response to Theiler's Virus Infection. Doctoral Dissertation. | Thesis individual record
abstract

A

growing

body

of

evidence

suggests

that

social

stress

contributes

to

the

pathogenesis

of

neurodegenerative

diseases,

such

as

multiple

sclerosis

(MS).

For

example,

prior

research

has

shown

that

social

disruption

(SDR)

stress

behaviorally

and

immunologically

exacerbates

Theiler's

murine

encephalomyelitis

virus

(TMEV)

infection.

TMEV

infection

results

in

acute

infection

of

the

central

nervous

system

(CNS)

followed

by

a

chronic

demyelinating

autoimmune

disease,

similar

to

that

seen

in

MS.

Research

suggests

that

social

stress

exerts

these

effects

by

altering

the

immune

response

to

infection.

More

specifically,

it

is

hypothesized

that

SDR

sensitizes

the

acute

inflammatory

response

to

infection

and

suppresses

T

cell

effector

function

in

the

acute

phase

of

disease.

It

was

demonstrated

that

SDR

is

sufficient

to

alter

inflammation.

Exposure

to

a

single

session

of

SDR

increases

IL---1?

mRNA

expression;

however,

IL---6

mRNA

expression,

but

not

IL---1?,

is

up

regulated

in

response

to

chronic

SDR.

Furthermore,

chronic

SDR

prior

to

infection

resulted

in

increased

infection

related

central

IL---6

and

IL---1?

mRNA

expression,

and

central administration

of

IL---6

neutralizing

antibody

during

SDR

reverses

this

increase

in

neuroinflammation.

This

suggests

that

SDR

sensitizes

infection

related

CNS

inflammation

through

an

up---regulation

of

IL---6.

Chronic

SDR

prior

to

infection

also

resulted

in

enhanced

CNS

viral

titers

and

suppression

of

virus---induced

CD4

and

CD8

T

cell

IFN---?

release

within

the

CNS.

As

a

whole,

this

research

indicates

that

SDR

exacerbates

the

disease

course

of

TMEV

infection

by

altering

the

central

innate

and

adaptive

immune

response

to

infection.

This

research

enhances

our

understanding

of

the

mechanisms

by

which

social

stress

exacerbates

neurodegenerative

disease

pathogenesis.

etd chair
publication date
2011