OBJECTIVEThe literature has shown that cognitive and emotional changes may occur after chronic treatment with glucocorticoids. This might be caused by the suppressive effect of glucocorticoids on hippocampal neurogenesis and cell proliferation. Paroxetine, a selective serotonin reuptake transporter, is a commonly used antidepressant for alleviation of signs and symptoms of clinical depression. It was discovered to promote hippocampal neurogenesis in the past few years and we wanted to investigate its interaction with glucocorticoid in this study.

METHODSAdult rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine for 14 d. Cell proliferation in the dentate gyrus was quantified using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry.

RESULTSThe corticosterone treatment suppressed while paroxetine treatment increased hippocampal cell proliferation. More importantly, paroxetine treatment could reverse the suppressive effect of corticosterone on hippocampal cell proliferation.

CONCLUSIONThis may have clinic application in preventing hippocampal damage after glucocorticoid treatment.

Analysis of Variance ; Animals ; Bromodeoxyuridine ; metabolism ; Cell Count ; Cell Proliferation ; drug effects ; Corticosterone ; pharmacology ; Drug Interactions ; Hippocampus ; cytology ; Male ; Neural Inhibition ; drug effects ; Neurons ; drug effects ; Paroxetine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Serotonin Uptake Inhibitors ; pharmacology

BACKGROUNDThe neurogenesis in retina of adult mammals is generally abolished, and this renders the retina lack of regenerative capacity. Despite this, there is a small population of nestin-positive cells in the ciliary epithelium which retains neurogenic potential. The present study aimed at investigating the effect of two drugs, corticosterone and paroxetine, on the cell proliferation of the ciliary body.

METHODSAdult Sprague-Dawley rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine treatment for 14 days. Cell proliferation in the ciliary body was quantified using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry. Co-labelling of BrdU and stem cell marker was used to phenotype the BrdU immunoreactive cells.

RESULTSCorticosterone treatment suppressed while paroxetine treatment increased the cell proliferation of the ciliary body. Co-labelling with cell markers revealed that the BrdU positive cells also showed nestin expression but not glial fibrillary acidic protein (GFAP).

CONCLUSIONSThe results illustrate that proliferation of retinal progenitor cells situated in ciliary body are subjected to regulation by selective serotonin reuptake inhibitors (SSRI) and corticosteroid, which is similar to our previous findings in neurogenic regions in central nervous system (CNS). Paroxetine treatment could reverse the suppressive effect of corticosterone on ciliary body cell proliferation. This provides information for future investigation of retinal stem cell biology and potential treatment of retinal degenerative diseases.

Adrenal Glands ; drug effects ; pathology ; Animals ; Body Weight ; drug effects ; Cell Proliferation ; drug effects ; Ciliary Body ; cytology ; drug effects ; Corticosterone ; pharmacology ; Immunohistochemistry ; In Vitro Techniques ; Male ; Organ Size ; drug effects ; Paroxetine ; pharmacology ; Rats ; Rats, Sprague-Dawley