LITHIUM ROBUSTLY INCREASES GLIAL PROLIFERATION

Within

the last few years, there has been tremendous progress in our understanding of

the critical roles of glial cells in regulating neuronal function as well as

their involvement in a variety of neuropsychiatric diseases.  There is now

compelling evidence that radial glial cells have the potential, not only to

guide newly born neurons, but also to self-renew and to generate both neurons

and astrocytes.  Furthermore, recent data has shown that astrocytes increase

the number of mature, functional synapses on CNS neurons by seven fold,

demonstrating that CNS synapse number can be profoundly regulated by glia. 

Glial cells are also known to play critical roles in regulating synaptic

glutamate levels, CNS energy homeostasis, liberation of trophic factors, and

indeed form dynamic, complex synaptic networks with neurons.  Nevertheless, the

possibility of glial dysfunction in major psychiatric disorders has only

recently received serious consideration due to the converging neuroimaging,

postmortem morphometric and microarray studies, which have clearly revealed

glial abnormalities in schizophrenia and mood disorders.  Here for the first

time, we have demonstrated that the astrocyte, whose proliferation is increased

by lithium, may indirectly (via liberation of factors from glial cells) regulate

neuronal differentiation.  Astrocytes may induce the pluripotent immature neuron

to express an astrocytic phenotype.  These mechanisms may provide a potential

target for improved long-term therapeutics for severe Neuropsychiatric