Lithium treatment causes gliosis and modifies the morphology of hippocampal astrocytes in rats

Abstract

The biological basis of the clinical efficacy of lithium in the treatment of mental illness has been extensively studied in neurones, but little is known about the effects of the drug on glia. Recently we showed that treatment of rats with clinically relevant doses of lithium chloride results in a 35% increase in the immunocontent of the astrocyte marker GFAP in the hippocampus. Here we studied the cytology of this phenomenon. Rats were treated for 4 weeks with a lithium diet which resulted in serum Li+ concentrations of 0.6-1.2 mmol/l. GFAP immunocytochemistry of the hippocampus revealed a mild gliosis in the CA1 area and the dentate gyrus which was associated with a change in the orientation of astrocytic processes. In control animals astrocyte processes were mainly orientated perpendicular to the stratum pyramidale, whereas in treated animals the cells were predominantly stellar in appearance.

Astroglial Plasticity in the Hippocampus is Affected by Chronic Psychosocial Stress and Concomitant Fluoxetine Treatment

“…After chronic lithium and antipsychotic medication, increased numbers of glia have been reported in the hippocampus and prefrontal cortex of rats and nonhuman primates (Rocha et al, 1998;Selemon et al, 1999). In contrast to that in our study, fluoxetine had no effect on hippocampal astrocyte numbers in control animals, but could counteract the stress-induced decrease of astrocyte numbers.…”

“…In contrast to that in our study, fluoxetine had no effect on hippocampal astrocyte numbers in control animals, but could counteract the stress-induced decrease of astrocyte numbers. Chronic treatment with lithium upregulates GFAP expression and modifies the morphology (orientation) of astrocytes (Rocha and Rodnight, 1994;Rocha et al, 1998). We report here that fluoxetine can reduce the somal volumes of astrocytes.…”

Reduced Glial Cell Density and Neuronal Size in the Anterior Cingulate Cortex in Major Depressive Disorder

“…11 There is also preliminary in vitro evidence that antidepressants activate microglia and cause proliferation of oligodendroglial cells, 53 and that lithium treatment is associated with gliosis. 54,55 Together, these findings suggest that our finding of reduced glial cell density is unlikely to be a consequence of pharmacological treatments or group differences in tissue pH.…”

Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice

“…Our data are supported by various reports showing a sustained increase in GFAP protein production up to 2 months following viral insult to the developing brain. 27,30 Increased GFAP production by astrocytes is a nonspecific indicator of injury since other types of injury such as lithium administration, 32 and trimethyltene exposure, 15,60 CO irradiation 33 and 6-OHDA and MPTP lesioning 34 may cause astrogliosis. Recent evidence supports the contention that abnormalities of astrocytic function may affect corticogenesis.…”