Protective effect of steroids in models of injury and Neurodegeneration: future applications to human neurological diseases

DE NICOLA A.F.

Albert Ludwig University, Freibur, Alemania

Conferencia; International Magister in Biomedical Sciences; 2009

Albert Ludwig University, Freiburg, Alemania

<!-- /* Font Definitions */ @font-face {font-family:"MS Mincho"; panose-1:2 2 6 9 4 2 5 8 3 4; mso-font-alt:"ＭＳ 明朝"; mso-font-charset:128; mso-generic-font-family:modern; mso-font-pitch:fixed; mso-font-signature:-1610612033 1757936891 16 0 131231 0;} @font-face {font-family:"@MS Mincho"; panose-1:2 2 6 9 4 2 5 8 3 4; mso-font-charset:128; mso-generic-font-family:modern; mso-font-pitch:fixed; mso-font-signature:-1610612033 1757936891 16 0 131231 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Arial; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:EN-GB; mso-fareast-language:ES; mso-bidi-language:AR-SA;} @page Section1 {size:595.3pt 841.9pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Transsynaptic neurodegeneration, a process suffered by motoneurons deafferented after spinal cord injury (SCI), is evidenced by chromatolysis, decreased expression of neurotrophins, neurotransmitters and enzymes. Concomitantly, astrocytes become reactive with upregulation of the glial fibrillary acidic protein (GFAP) whereas oligodendrocytes are damaged with depletion of myelin proteins. We studied the effects of progesterone treatment in the context of SCI, because under these conditions the spinal cord becomes a progesterone target. Previous work demonstrated progesterone´s neuroprotective and promyelinating effects after SCI. Whereas a 3 day-course of progesterone treatment at 4 mg/kg did not modify GFAP+ astrocytosis in gray or white matter after SCI, 16 mg/kg down-regulated GFAP+-astrogliosis. The effects of SCI also involved the astrocyte proteins vimentin and acquaporin4 (AQP4). Vimentin showed a marked upregulation after SCI in the central canal, radial glia and some hypertrophied astrocytes. This scenario was attenuated following high dose progesterone treatment. SCI also increased the expression of AQP4, its colocalization with GFAP in astrocyte end-feet on microvessels, and produced edema. Progesterone decreased edema and attenuated AQP4 staining. Another cells responding to progesterone in rats with SCI were the NG2+ oligodendrocyte precursor cells (OPC). They increased in number while myelin proteins were repleted. This dual effect of progesterone on astrocytes and OPC suggests that hormonal intervention to diminish reactive astrogliosis, as shown by three different markers (GFAP, vimentin, ACQP) may be temporally and functionally related to enhancement of oligodendrocyte function and remyelination. Therefore, progesterone neuroprotection after SCI engages different cell types, some being deactivated like astrocytes, while functions of neurons and oligodendrocytes are activated.