Producción CyT
Artículo
Autoría
Meyer, M.
;
Garay, L.I.
;
Kruse, M. S.
;
Gargiulo Monachelli, G.
;
Lara, A.
;
Schumacher, M.
;
Guennoun, R.
;
COIRINI, HECTOR
;
De Nicola, A.F.
;
Gonzalez Deniselle, M.C.
Fecha
2015
Editorial y Lugar de Edición
Wiley
Revista
JOURNAL OF NEUROCHEMISTRY
Wiley
Resumen
Información suministrada por el agente en
SIGEVA
Previous work hasshown that progesterone (PROG) treatment of Wobbler (WR) mice prevents several abnormalities of the spinalcord. PROG is partly metabolized into allopregnanolone (ALLO), a neurosteroidthat mediates some effects of the parent molecule. In the present study, weanalyzed in the cervical spinal cord the effects of PROG or ALLO treatment in Wobbler mice atearly stages of the disease on neuronal expressionof brain derived neurotrophic factor (BDNF), its cognate receptor TrkB and the &#...
Previous work hasshown that progesterone (PROG) treatment of Wobbler (WR) mice prevents several abnormalities of the spinalcord. PROG is partly metabolized into allopregnanolone (ALLO), a neurosteroidthat mediates some effects of the parent molecule. In the present study, weanalyzed in the cervical spinal cord the effects of PROG or ALLO treatment in Wobbler mice atearly stages of the disease on neuronal expressionof brain derived neurotrophic factor (BDNF), its cognate receptor TrkB and the 3 subunit of Na+, K+-ATPase mRNAs,the phosphorylation of AKT and JNK kinases, the activity of nitric oxidesynthase (NOS), and immunoreactivity (IR) of low affinity p75NTR and cholineacetyltransferase (ChAT). Motoneuron morphology and clinical parameters werealso evaluated. Treatment protocols involved a short exposure to a PROG pelletfor 18 days or to ALLO given by daily injections for 5 days, whereas prolongedtreatment involved exposure to a PROG pellet for 60 days or 16 injections of ALLOevery two days during 32 days. Wobbler mice at early stages of the disease showedreduction of pAKT and 3Na+, K+-ATPase mRNA and NOS hyperactivity, all of which were prevented byshort-term PROG or ALLO treatment. Short-term steroid treatment significantlyincreased TrkB mRNA in Wobbler motoneurons, whereas long lasting steroidadministration enhanced BDNF, TrkB mRNAs and IR-ChAT and decreased pJNK. Bothtreatment protocols down-regulated IR-p75NTR and reduced motoneuronvacuolation. Long-term PROG or ALLO treatment attenuated grey matter astrogliosisand enhanced motor performance. Collectively, these findings indicated thatPROG and ALLO similarly rescued motoneurons from degeneration. Down regulationof NOS activity and p75NTR hyperexpression, associated to modulation ofpJNK/pAKT and neurotrophic factor pathways might underlie the steroid protectiveeffects. These data support that ALLO treatment exerts beneficial effects for spinalcord neurodegeneration.
Ver más
Ver menos
Palabras Clave
NEUROPATHOLOGYMOTONEURONE DEGENERATIONALLOPREGNENOLONEWOBBLER