Progesterone upregulates neuronal brain derived neurotrophic factor expression in the injured spinal cord

GONZALEZ S; LABOMBARDA F; GONZALEZ DENISELLE, C; GENOUUN R; SCHUMACHER M; DE NICOLA A

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2004 vol. 125 p. 605 - 614

0306-4522

Abstract—Progesterone (PROG) provides neuroprotection tothe injured central and peripheral nervous system. Theseeffects may be due to regulation of myelin synthesis in glialcells and also to direct actions on neuronal function. Recentstudies point to neurotrophins as possible mediators of hormoneaction. Here, we show that the expression of brainderivedneurotrophic factor (BDNF) at both the mRNA andprotein levels was increased by PROG treatment in ventralhorn motoneurons from rats with spinal cord injury (SCI).Semiquantitative in situ hybridization revealed that SCI reducedBDNF mRNA levels by 50% in spinal motoneurons(control: 53.5
7.5 grains/mm2 vs. SCI: 27.5
1.2, P<0.05),while PROG administration to injured rats (4 mg/kg/day during3 days, s.c.) elicited a three-fold increase in grain density(SCIPROG: 77.8
8.3 grains/mm2, P<0.001 vs. SCI). In addition,PROG enhanced BDNF immunoreactivity in motoneuronsof the lesioned spinal cord. Analysis of the frequencydistribution of immunoreactive densities (2: 812.73,P<0.0001) showed that 70% of SCIPROG motoneuronsscored as dark stained whereas only 6% of neurons in the SCIgroup belonged to this density score category (P<0.001).PROG also prevented the lesion-induced chromatolytic degenerationof spinal cord motoneurons as determined byNissl staining. In the normal intact spinal cord, PROG significantlyincreased BDNF inmunoreactivity in ventral horn neurons,without changes in mRNA levels. Our findings suggestthat PROG enhancement of endogenous neuronal BDNFcould provide a trophic environment within the lesioned spinalcord and might be part of the PROG activated-pathwaysto provide neuroprotection.