Divergent effects of ovarian steroids on neuronal survival during experimental allergic encephalitis in Lewis rats

Citation
Ge. Hoffman et al., Divergent effects of ovarian steroids on neuronal survival during experimental allergic encephalitis in Lewis rats, EXP NEUROL, 171(2), 2001, pp. 272-284
Citations number
62
Categorie Soggetti
Neurosciences & Behavoir
Journal title
EXPERIMENTAL NEUROLOGY
ISSN journal
00144886 → ACNP
Volume
171
Issue
2
Year of publication
2001
Pages
272 - 284
Database
ISI
SICI code
0014-4886(200110)171:2<272:DEOOSO>2.0.ZU;2-S
Abstract
Experimental allergic encephalitis, (EAE) a Th1-cell-dependent autoimmune d isease of the central nervous system (CNS) used to study immune responses r elevant to multiple sclerosis (MS) displays gender susceptibility. The unde rlying basis of the sexual dimorphism may reflect multiple factors includin g gender-specific hormones. To study the relationship between ovarian hormo nes and CNS inflammation, we induced EAE in susceptible female Lewis rats o variectomized (OVX) 7 days earlier and implanted with blank capsules or cap sules containing estradiol (E), progesterone (P), or both (EP). Rats were i mmunized with complete Freunds' adjuvant alone or combined with guinea pig myelin basic protein. Motor function was scored 0-5 on standard criteria (d ays 7-11 postimmunization). On day 11, the rats were euthanized and the lum bar spinal cord was analyzed for Nissl, neuron nuclear antigen, and DNA fra gmentation with a TUNEL assay. Inflammation was judged qualitatively on a s cale of 0-4. Our immunization protocol induced limited sensorimotor deficit s in OVX rats (2.3 +/- 0.6, mean +/- SEM) with moderate inflammation (2.5 /- 0.4). E limited both behavioral impairments (1.0 +/- 0.4) and inflammati on (0.5 +/- 0.2). P-treated rats had more severe sensorimotor deficits (3.1 +/- 0.5) with increased inflammatory infiltrates (3.6 +/- 0.4) and markedl y increased numbers of TUNEL+ neurons. Neuron counts of the outer two Rexed lamina (L3-L5) showed a 20% neuron loss (P < 0.02) in P-treated rats with EA in comparison to other groups. Coadministration of E with P prevented th e consequences of P, including neuronal apoptosis (behavioral score, 0.6 +/ - 0.6; inflammation, 1.4 +/- 0.5). Our results suggest a potential and nove l function of P that increases the vulnerability of neurons to apoptotic in jury in EAE and may have pathophysiologic implications in the progression o f disability in women with MS. (C) 2001 Academic Press.