Cells that clear damage in the brain are less active
in alcohol-dependent patients after withdrawal than
in models of adolescent binge-drinking.
People who have become alcohol-dependent suffer
symptoms of withdrawal while abstaining from drink.
These include cognitive impairment, such as memory
problems, making plans and being able to act
Previous evidence from research in mice has
suggested that these impairments might be caused by
the over-activity of cells called microglia.
Microglia maintain the brain by removing damaged
neurons and synapses and fighting infections.
However, excess microglia activity can be harmful,
producing chemicals that cause collateral damage to
healthy nerve cells. This process is implicated in
brain disorders such as Alzheimer's and Parkinson’s
Microglia activity has previously been found in
experiments to increase after mice are given high
doses of alcohol which make them suffer from
withdrawal symptoms. This led researchers to ask
whether the same damaging process was occurring in
middle-aged alcohol dependents suffering withdrawal.
Finding the opposite of what was expected.
To investigate, a team led by Imperial College
London and Kings College London scanned the brains
of alcohol-dependent patients and healthy volunteers
looking for microglial activity.
What they found was the opposite of what they
expected. The experiment revealed that
alcohol-dependent patients abstaining from alcohol
actually show less microglial activity than healthy
They also found that in healthy people, the greater
the levels of microglial activity in the
hippocampus, the better their memories were.
The team believe the discrepancy between the mouse
models and the human subjects might be because mouse
models of alcohol abstinence better represent
adolescent binge-drinkers, rather than middle-aged
The results point to a different role for microglial
activity. The team suggest that in adolescent
binge-drinking mice, the surge of microglial
activity may help to restore the hippocampus, the
area of the brain involved in memory.
In the brains of human alcohol-dependent patients,
this activity is dampened, either because the
microglia are not functioning properly or because
they have been lost.
The team’s result supports other research that shows
that microglial over-activity might not always be
harmful, and that there might be two types of
activity that either cause damage or cause repair.
It also suggests that in some cases, interventions
should be trying to boost the activity of microglia,
rather than dampen it as all current therapies do.
Study author Dr Nicola Kalk, from the National
Addictions Centre at King’s College London and the
Division of Brain Sciences at Imperial, said:
“Previous knowledge suggested that we would find
greater microglial activity in alcohol-dependent
patients’ brains, but in fact we found the opposite.
"Combined with our other finding – that microglial
activity was associated with better memory in
healthy volunteers – this led us to consider the
idea that microglial activity can sometimes have a
positive effect on cognitive function that is lost
in alcohol-dependent patients.”
To determine microglial activity, the team compared
the brain scans of healthy volunteers and patients
with alcohol dependence. They used a technique
called positron emission tomography that allowed
them to quantify the microglial activity in each
volunteer’s hippocampus. The results of the study
were published in the journal Translational
Professor Anne Lingford-Hughes, from the Centre for
Psychiatry at Imperial, said: “This is an important
study to help us understand what processes are
involved in the damaging effects of alcohol on the
brain. Without this knowledge we will not be able to
develop treatment strategies to improve brain
recovery to optimise cognitive function.”
For more information
Decreased hippocampal translocator protein (18?kDa)
expression in alcohol dependence: a [11C]PBR28 PET
N J Kalk, Q Guo, D Owen, R Cherian, D Erritzoe, A
Gilmour, A S Ribeiro, J McGonigle, A Waldman, P
Matthews, J Cavanagh, I McInnes, K Dar, R Gunn, E A
Rabiner and A R Lingford-Hughes