Glucocorticoid regulation of motoneuronal parameters in rats with spinal cord injury.
1. Glucocorticoids exert beneficial effects after acute CNS injury in humans and experimental animals. To elucidate potential mechanisms of glucocorticoid action in the lesioned spinal cord, we have studied if treatment with dexamethasone (DEX) modulated the neurotrophin binding receptor p75 (p75NTR) and choline acetyltransferase (ChAT), a marker of neuronal functional viability. 2. Rats with a sham operation or with spinal cord transection at the thoracic level received vehicle or DEX several times postlesion and were sacrificed 48 hr after surgery. The lumbar region caudal to the lesion was processed for p75NTR and ChAT immunoreactivity (IR) using quantitative densitometric analysis. 3. We observed that p75NTR-IR was absent from ventral horn motoneurons of sham-operated rats, in contrast to strong staining of neuronal perikaryon in TRX rats. Administration of DEX to TRX rats had no effect on the number of neuronal cell bodies expressing p75NTR-IR but significantly increased the number and length of immunostained neuronal processes. 4. Furthermore, spinal cord transection reduced ChAT immunostaining of motoneurons by 50%, whereas DEX treatment reverted this pattern to cells with a strong immunoreaction intensity in perikaryon and cell processes. 5. It is hypothesized that increased expression of p75NTR in cell processes and of ChAT in motoneurons may be part of a mechanism by which glucocorticoids afford neuroprotection, in addition to their known antiinflammatory effects.
Gonzalez
S L
SL
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, UBA-CONICET, Argentina.
Saravia
F
F
Gonzalez Deniselle
M C
MC
Lima
A E
AE
De Nicola
A F
AF
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism*
D005938:Glucocorticoids; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D003907:Dexamethasone; D002795:Choline O-Acetyltransferase