title: Progesterone effects on neuronal brain-derived neurotrophic factor and glial cells during progression of Wobbler mouse neurodegeneration.
abstract: Previous results have shown a depletion of brain-derived neurotrophic factor (BDNF) mRNA in the degenerating motoneurons from clinically afflicted Wobbler mice, whereas progesterone treatment reverts this depletion. We now compared progesterone regulation of BDNF in motoneurons and oligodendrocytes of Wobbler mice at the progressive (EP, 1-3 months), symptomatic (SYM, 5-8 months old), and late stages (LS, 12-13 months). As controls we used NFR/NFR mice. Controls and Wobbler mice of different ages remained untreated or received a 20 mg progesterone pellet during 18 days. BDNF mRNA was determined in the ventral, intermediolateral, and dorsal gray matter by film autoradiography and in motoneurons using in situ hybridization. A depletion of BDNF mRNA already occurred at the EP stage of Wobblers, but progesterone was inactive at this period. In contrast, progesterone upregulated the low levels of BDNF mRNA in SYM Wobblers in the three gray matter regions analyzed. Progesterone also increased BDNF mRNA in LS Wobblers, according to grain counting procedures. BDNF protein analyzed by enzyme-linked immunosorbent assay (ELISA) in ventral horns or immunostaining of motoneurons was normal in steroid-naive SYM Wobblers. BDNF protein was decreased by progesterone, suggesting increased anterograde transport and/or release of neuronal BDNF. Wobbler mice also showed depletion of CC1-immunopositive oligodendrocytes, whereas progesterone treatment enhanced the density of BDNF+ and CC1+ oligodendrocytes in EP, SYM, and LS Wobblers. Our results suggest that BDNF could be involved in progesterone effects on motoneurons at the SYM and LS periods, whereas effects on oligodendrocytes occurred at all stages of the Wobbler disease. These steroid actions may be important to arrest the ongoing neurodegeneration.
authors: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental-CONICET, Obligado 2490, 1428 Buenos Aires, Argentina.
authors: M
authors: M
authors: Meyer
authors: M C
authors: MC
authors: Gonzalez Deniselle
authors: G
authors: G
authors: Gargiulo-Monachelli
authors: L I
authors: LI
authors: Garay
authors: M
authors: M
authors: Schumacher
authors: R
authors: R
authors: Guennoun
authors: A F
authors: AF
authors: De Nicola
mesh_terms: D000367:Age Factors; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000235:genetics; D051379:Mice; D008818:Mice, Neurologic Mutants; D016472:Motor Neuron Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009154:Mutation; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; C486750:Vps54 protein, mouse; D011374:Progesterone