title: Effects of the SARM ACP-105 on rotorod performance and cued fear conditioning in sham-irradiated and irradiated female mice.
abstract: Female mice are more susceptible to radiation-induced cognitive changes than male mice. Previously, we showed that, in female mice, androgens antagonize age-related cognitive decline in aged wild-type mice and androgens and selective androgen receptor modulators (SARMs) antagonize cognitive changes induced by human apolipoprotein E4, a risk factor for developing age-related cognitive decline. In this study, the potential effects of the SARM ACP-105 were assessed in female mice that were either sham-irradiated or irradiated with ¹³⁷Cesium at a dose of 10Gy. Behavioral testing started 2 weeks following irradiation. Irradiation impaired sensorimotor function in vehicle-treated mice but not in ACP-105-treated mice. Irradiation impaired cued fear conditioning and ACP-105 enhanced fear conditioning in sham-irradiated and irradiated mice. When immunoreactivity for microtubule-associated protein 2 was assessed in the cortex of sham-irradiated mice, there was a brain area × ACP-105 interaction. While ACP-105 reduced MAP-2 immunoreactivity in the sensorimotor cortex, there was a trend towards increased MAP-2 immunoreactivity in the enthorhinal cortex. No effect on MAP-2 immunoreactivity was seen in the irradiated cortex or sham-irradiated or irradiated hippocampus. Thus, there are relatively early radiation-induced behavioral changes in female mice and reduced MAP-2 levels in the sensorimotor cortex following ACP-105 treatment might contribute to enhanced rotorod performance.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dayger
authors.forename: Laura
authors.initials: L
authors.lastname: Villasana
authors.forename: Timothy
authors.initials: T
authors.lastname: Pfankuch
authors.forename: Matthew
authors.initials: M
authors.lastname: Davis
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D003214:Conditioning, Classical / Q000187:drug effects* / Q000528:radiation effects; D005239:Fear / Q000187:drug effects* / Q000528:radiation effects; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects* / Q000528:radiation effects; D045442:Rotarod Performance Test; D016708:Synaptophysin / Q000378:metabolism
chemical_list: C545686:2-chloro-4-(3-hydroxy-3-methyl-8-azabicyclo(3.2.1)oct-8-yl)-3-methylbenzonitrile; D053961:Azabicyclo Compounds; D008869:Microtubule-Associated Proteins; D016708:Synaptophysin