Female mice are protected from space radiation-induced maladaptive responses

Karen Krukowski; Katherine Grue; Elma S Frias; John Pietrykowski; Tamako Jones; Gregory Nelson; Susanna Rosi

doi:10.1016/j.bbi.2018.08.008

Female mice are protected from space radiation-induced maladaptive responses

Brain Behav Immun. 2018 Nov:74:106-120. doi: 10.1016/j.bbi.2018.08.008. Epub 2018 Aug 11.

Authors

Karen Krukowski¹, Katherine Grue¹, Elma S Frias², John Pietrykowski¹, Tamako Jones³, Gregory Nelson³, Susanna Rosi⁴

Affiliations

¹ Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA, USA; Brain and Spinal Injury Center, University of California, San Francisco, CA, USA.
² Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA, USA; Brain and Spinal Injury Center, University of California, San Francisco, CA, USA; Biomedical Science Graduate Program, University of California, San Francisco, CA, USA.
³ Department of Basic Sciences, Division of Biomedical Engineering Sciences, Loma Linda University, Loma Linda, CA,USA.
⁴ Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA, USA; Brain and Spinal Injury Center, University of California, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, CA, USA; Weill Institute for Neuroscience, University of California, San Francisco, CA, USA; Kavli Institute of Fundamental Neuroscience, University of California, San Francisco, CA, USA. Electronic address: susanna.rosi@ucsf.edu.

Abstract

Interplanetary exploration will be humankind's most ambitious expedition and the journey required to do so, is as intimidating as it is intrepid. One major obstacle for successful deep space travel is the possible negative effects of galactic cosmic radiation (GCR) exposure. Here, we investigate for the first time how combined GCR impacts long-term behavioral and cellular responses in male and female mice. We find that a single exposure to simulated GCR induces long-term cognitive and behavioral deficits only in the male cohorts. GCR exposed male animals have diminished social interaction, increased anxiety-like phenotype and impaired recognition memory. Remarkably, we find that the female cohorts did not display any cognitive or behavioral deficits after GCR exposure. Mechanistically, the maladaptive behavioral responses observed only in the male cohorts correspond with microglia activation and synaptic loss in the hippocampus, a brain region involved in the cognitive domains reported here. Furthermore, we measured reductions in AMPA expressing synaptic terminals in the hippocampus. No changes in any of the molecular markers measured here are observed in the females. Taken together these findings suggest that GCR exposure can regulate microglia activity and alter synaptic architecture, which in turn leads to a range of cognitive alterations in a sex dependent manner. These results identify sex-dependent differences in behavioral and cognitive domains revealing promising cellular and molecular intervention targets to reduce GCR-induced chronic cognitive deficits thereby boosting chances of success for humans in deep space missions such as the upcoming Mars voyage.

Keywords: Galactic cosmic ray; Microglia; Radiation; Sex-differences; Synapse.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Behavior, Animal / radiation effects*
Cognitive Dysfunction / physiopathology
Cosmic Radiation / adverse effects*
Female
Male
Mice
Mice, Inbred C57BL
Microglia / radiation effects
Models, Animal
Sex Factors*
Space Flight
Synapses / radiation effects

Abstract

Publication types

MeSH terms

Grants and funding