Fluoxetine treatment reverses several hippocampal alterations in streptozotocin diabetic mice.

BEAUQUIS, J; ROIG, P; GARAY, L; LABOMBARDA, F.; GONZALEZ, SUSANA; HOMO-DELARCHE, F; DE NICOLA, AF; SARAVIA F.

Madrid, España

Congreso; Congreso Iberoamericano de Neuroinmunomodulación; 2007

Fluoxetine treatment reverses several hippocampal alterations in streptozotocin diabetic mice. J. Beauquisa, P. Roiga, L.Garaya,b, F. Labombardaa,b, S. Gonzáleza,b, F. Homo-Delarchec, A. F. De Nicolaa,b, F. Saraviaa,b. aInstitute of Biology and Experimental Medicine, National Research Council of Argentina, bMedical School, University of Buenos Aires. cCNRS 7059 Paris, France.   Diabetes mellitus is associated with brain alterations that constitute the diabetic encephalopathy and shares many characteristics with depression. We have reported that fluoxetine -an antidepressant, serotonin reuptake inhibitor- treatment was able of correcting the poor hippocampal proliferation rate in the dentate gyrus of streptozotocin diabetic mice, a pharmacological model of type 1 diabetes. Here, we report that fluoxetine treatment increased the survival of new neurons in diabetic animals using the bromodeoxyuridine labeling technique. Neural phenotype was confirmed by co-labeling with specific markers. The number of pyknotic cells showed a marked increase in diabetic mice. Content of BDNFmRNA -linked to neurogenesis and cell survival- by in situ hybridization, was low in the dentate gyrus of diabetic animals and increased by fluoxetine. Although the function and regulation of NG2+ cells is controversial, the proteoglycan NG2 is associated to axonal growth inhibition and neurodegeneration. The number of NG2+ cells in the hilus of diabetic mice increased compared with controls and antidepressant decreased it. This work displays new evidence of hippocampal alterations in diabetes, a metabolic disease, reporting decreased cell survival, increased cell loss and suffering and glial reactivity, and declined neurotrophic factor expression. Fluoxetine reversed these changes, suggesting a protective role of the antidepressant in the brain.