Progesterone improves neurocognitive outcomes following therapeutic cranial irradiation in mice.

Abstract

Despite improved therapeutic methods, CNS toxicity resulting from cancer treatment remains a major cause of post-treatment morbidity. More than half of adult patients with cranial irradiation for brain cancer develop neurobehavioral/cognitive deficits that severely impact quality of life. We examined the neuroprotective effects of the neurosteroid progesterone (PROG) against ionizing radiation (IR)-induced neurobehavioral/cognitive deficits in mice. Male C57/BL mice were exposed to one of two fractionated dose regimens of IR (3Gy×3 or 3Gy×5). PROG (16mg/kg; 0.16mg/g) was given as a pre-, concurrent or post-IR treatment for 14days. Mice were tested for short- and long-term effects of IR and PROG on neurobehavioral/cognitive function on days 10 and 30 after IR treatment. We evaluated both hippocampus-dependent and -independent memory functions. Locomotor activity, elevated plus maze, novel object recognition and Morris water maze tests revealed behavioral deficits following IR. PROG treatment produced improvement in behavioral performance at both time points in the mice given IR. Western blot analysis of hippocampal and cortical tissue showed that IR at both doses induced astrocytic activation (glial fibrillary acidic protein), reactive macrophages/microglia (CD68) and apoptosis (cleaved caspase-3) and PROG treatment inhibited these markers of brain injury. There was no significant difference in the degree of deficit in any test between the two dose regimens of IR at either time point. These findings could be important in the context of patients with brain tumors who may undergo radiotherapy and eventually develop cognitive deficits.

• Authors: Seema Yousuf, Daniel J Brat, Hui-Kuo Shu, Ya Wang, Donald G Stein, Fahim Atif
• Journal: Hormones and behavior (Horm Behav) Vol. 96 Pg. 21-30 (11 2017) ISSN: 1095-6867 [Electronic] United States
• PMID: 28866326 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Neuroprotective Agents
• Progesterone

Topics

• Animals
• Brain Injuries (complications, etiology, prevention & control)
• Cognition (drug effects)
• Cognition Disorders (etiology, prevention & control)
• Cranial Irradiation (adverse effects, psychology)
• Hippocampus (drug effects)
• Male
• Maze Learning (drug effects)
• Memory (drug effects)
• Mice
• Mice, Inbred C57BL
• Microglia (cytology, drug effects)
• Neurogenesis (drug effects)
• Neuroprotective Agents (pharmacology)
• Progesterone (pharmacology)
• Quality of Life
• Radiation Injuries, Experimental (etiology, prevention & control)
• Treatment Outcome