Reinterpretation of Mouse Thyroid Changes under Space Conditions: The Contribution of Confinement to Damageby E. Albi, F.S. Ambesi-Impiombato, A. Lazzarini, R. Lazzarini, A. Floridi, S. Cataldi, E. Loreti, I. Ferri, F. Curcio

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Reinterpretation of Mouse Thyroid Changes under Space Conditions:

The Contribution of Confinement to Damage

E. Albi,1 F.S. Ambesi-Impiombato,2 A. Lazzarini,1,2 R. Lazzarini,1 A. Floridi,1 S. Cataldi,1

E. Loreti,3 I. Ferri,3 and F. Curcio2

Abstract

During space missions, astronauts work in a state of separation from their daily social environment and in physical confinement. It has been shown that confinement influences mood and brain cortical activity, but no data has been obtained with regard to its effect on the thyroid gland, the structure and function of which change during spaceflights. Here, we report the results of a study on the effects of confinement on mouse thyroid, which was implemented with the Mice Drawer System Facility maintained on the ground, a system used for spaceflight experiments. The results show that confinement changes the microscopic structure of the thyroid gland and that it exhibits symptoms similar to those that result from physiological and/or pathological hyperfunction.

What is left unchanged, however, is the sphingomyelinase-thyrotropin receptor relationship, which is important for thyrotropin response with a consequential production of hormones that act on the metabolism of almost all tissues and reduces the production of calcitonin, a hormone involved in bone metabolism. During space missions, the overexpression of pleiotrophin, a widespread cytokine up-regulated after tissue injury that acts on bone remodeling, attenuates changes to the thyroid that are spaceflight-dependent; therefore we studied the thyroids of pleiotrophin-transgenic mice in the Mice Drawer System Facility. In confinement, pleiotrophin overexpression does not protect from the loss of calcitonin. The contribution of confinement to thyroid damage during spaceflights is discussed. Key Words: Calcitonin—Confinement—Sphingomyelinase—Thyroid—

Thyrotropin receptor. Astrobiology 14, 563–567. 1. Introduction

During space missions, astronauts are separated fromtheir daily life and forced to live in a confined space for long periods of time (Palinkas, 2001). It is generally believed that confinement represents a potential hazardous condition for acute and/or traumatic physical injury (Yue et al., 2012).

It induces the reduction of hearing and balance (Dechesne et al., 1993) and changes the mood and brain cortical activity (Schneider et al., 2010), mental performance (Manzey and

Lorenz, 1998), and brain electrical activity (Lorenz et al., 1996). Little is known about the effects of confinement on the body’s equilibrium over long periods of time, which, under such conditions, is very likely to be subject to significant perturbations in space, as has already been reported with regard to pathological variations in the bodily functions of astronauts (Rowe, 2009; Smith et al., 2012; Mermel, 2013).

The body’s equilibrium largely depends on proper coordination of the endocrine system (Michelson et al., 1994).

Since the thyroid is an endocrine gland that produces hormones that control the metabolism of almost all tissues, thyroid function impairment may be explained by tissue damage astronauts suffer during space missions (Masini et al., 2012). The thyroid gland is composed of spherical follicles surrounded by a single layer of thyroid epithelial cells (thyrocytes) that secrete T3 and T4 hormones that control metabolism of the cardiovascular, musculoskeletal, immune, and nervous systems. Also, parafollicular cells (C cells) in the thyroid secrete calcitonin, which acts on bone metabolism. In the present study, we investigated the role of confinement on changes in the thyroid gland. Previously, we studied the effect of the space environment on the thyroid of mice that were maintained for 91 days on board the International Space Station (ISS). This was in participation with 1Laboratory of Nuclear Lipid BioPathology, CRABiON, Perugia, Italy. 2Department of Clinical and Biological Sciences, University of Udine, Udine, Italy. 3Institute of Pathologic Anatomy and Histology, University of Perugia, Perugia, Italy.

ASTROBIOLOGY

Volume 14, Number 7, 2014 ª Mary Ann Liebert, Inc.

DOI: 10.1089/ast.2014.1166 563 the Tissue Sharing team, which was led by R. Cancedda (Cancedda et al., 2012). We demonstrated that, in comparison with control animals, thyroids of spaceflight animals had a more homogenous structure; produced more cAMP; and expressed more thyrotropin receptor (TSHR) and caveolin1 (Masini et al., 2012), sphingomyelinase (SMase), and sphingomyelin-synthase (Albi et al., 2012a). Spaceflight animal thyroids, however, were also characterized by a loss of C cells with a reduction in calcitonin production (Albi et al., 2012b). In these experiments, the animals were maintained during the flight in the Mice Drawer System (MDS), a facility built by Thales Alenia Space-Italy for the

Agenzia Spaziale Italiana. As reported by R. Cancedda et al. (2012), the mice were hosted in the Mice Chamber, which was divided into two habitats. Each habitat permitted accommodation of the items necessary to provide three individually housed mice with basic services, such as three metallic cages, three food envelopes, three drinking valves for water delivery, three cameras for video observation, white and infrared LEDs for illumination, and sensors for air composition monitoring and control. The cages had grids in all four walls, which permitted olfactory, but not physical, contact between animals. In our previous studies (Albi et al., 2012a, 2012b; Masini et al., 2012), we did not consider the possibility that the results obtained after the return from space might have been due, in part, to the effect of confinement.

Here, we focused our attention on the difference between the thyroids of mice that were housed for 3 months in the MDS and those of mice housed for the same period of time in normal vivarium cages at the Vivarium of the Advanced

Biotechnology Center in Genoa, Italy. 2. Materials and Methods

Experimental design, authorization of experimental procedures, and animal care were as previously reported (Albi et al., 2012b; Masini et al., 2012).