IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
MOLECULAR AND BEHAVIORAL EVIDENCES FOR PROGESTERONE AND NEUROSTEROID PROTECTION IN MOTONEURON DEGENERATION
Autor/es:
DE NICOLA, A.F; GONZALEZ DENISELLE, M.C; MEYER, M; GARGIULO, G; GUENNOUN R; SCHUMACHER,M
Lugar:
Sardinia
Reunión:
Simposio; International Behavioral Neuroscience Society; 2010
Resumen:
The effects of progesterone in
nervous system diseases are of increasing interest due to their potential
clinical applications. We have studied progesterone neuroprotection in Wobbler
mouse spinal cord degeneration. Wobblers present motoneuron vacuolation,
astrogliosis, atrophic limbs, tremor and ambulatory difficulty that worsens
with disease progression. Wobbler motoneurons show impaired expression of
brain-derived neurotrophic factor (BDNF), choline acetyltransferase (ChAT) and
Na,K-ATPase and increased expression of nitric oxide synthase (NOS).
Mitochondria show vacuolation, edema and crystolysis, decreased activity of
respiratory chain complex I activity and increased expression of mitochondrial
NOS (mtNOS). In 5-8 month-old Wobblers, at the established stage of the
disease, progesterone reverses these abnormalities. Progesterone effectiveness
has also been studied at early (12 months) and late (12 months) stages of
neurodegeneration. In untreated Wobblers, vacuolated motoneurons are initially
abundant, experience a slight reduction at the established stage and
dramatically diminish during the late period. ChAT and BDNF are reduced at all
stages of the Wobbler disease. Progesterone significantly reduces motoneuron
vacuolation, enhances ChAT immunoreactivity during the early progressive and
established stages, whereas up regulation of BDNF occurs at the established and
late periods. Untreated Wobblers show high density of glial fibrillary acidic
protein (GFAP) astrocytes, which are down-regulated by progesterone at all
stage periods. Long-term progesterone treatment enhances survival and muscle
strength, according to the time spent on a vertical grid and on a horizontal
rope test. Therefore, progesterone may constitute a novel therapeutic tool to
attenuate the course of neurodegeneration. Studies are in progress to study
progesterone effects in patients with amyotrophic lateral sclerosis.