Core body temperature varies according to the time of exercise without affecting orexin-A production in the dorsal hypothalamus in male rats.

Physical exercise differentially increases body temperature according to the time of day, which shows the importance of circadian rhythm in thermal regulation. Given its contribution in central pathways involved in thermoregulation, orexin A could play a role in the regulation of core body temperature during and after exercise. To test this hypothesis, we assessed the effect of exercise, performed at two times of day, on core temperature and on the amount of orexin A in the production zone, i.e., the dorsal hypothalamus. Forty-nine male Wistar rats underwent forced treadmill exercise during the HG phase and HL phase of core temperature. Basal core temperature was recorded continuously for 48 h by implanted telemetric sensors in 11 rats. Regulation of core temperature during exercise (20 min) and after each exercise (60 min) was modeled with a modified logistic-type function. During HG exercise, core temperature curve reached a significantly higher maximum (asymptote: +0.70 ± 0.10 °C) and took longer to attain the strongest inclination of the core temperature regulation curve (Xmid: 3.46 ± 0.72 min). After HG exercise, time of recovery was significantly longer than after HL exercise. In male rats, thermoregulatory response to acute physical exercise was influenced by the time of day. There was no effect of either physical activity or time of day on the level of orexin A in the dorsal hypothalamus. Our results suggest that orexin A in the dorsal hypothalamus is not involved in the effects of physical exercise on thermoregulation.

Effects of long-term methylphenidate treatment in adolescent and adult rats on hippocampal shape, functional connectivity and adult neurogenesis.

Methylphenidate (MPH) is a widely prescribed stimulant drug for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents. Its use in this age group raises concerns regarding the potential interference with ongoing neurodevelopmental processes. Particularly the hippocampus is a highly plastic brain region that continues to develop postnatally and is involved in cognition and emotional behavior, functions known to be affected by MPH. In this study, we assessed whether hippocampal structure and function were affected by chronic oral MPH treatment and whether its effects were different in adolescent or adult rats. Using behavioral testing, resting-state functional MRI, post-mortem structural magnetic resonance imaging (MRI), and immunohistochemistry, we assessed MPH's effects on recognition memory, depressive-like behavior, topological features of functional connectivity networks, hippocampal shape and markers for hippocampal neurogenesis and proliferation. Object recognition memory was transiently impaired in adolescent treated rats, while in animals treated during adulthood, increased depressive-like behavior was observed. Neurogenesis was increased in adolescent treated rats, whereas cell proliferation was decreased following adult treatment. Adolescent treated rats showed inward shape deformations adjacent to ventral parahippocampal regions known to be involved in recognition memory, whereas such deformations were not observed in adult treated animals. Irrespective of the age of treatment, MPH affected topological features of ventral hippocampal functional networks. Thus, chronic oral treatment with a therapeutically relevant dose of MPH preferentially affected the ventral part of the hippocampus and induced contrasting effects in adolescent and adult rats. The differences in behavior were paralleled by opposite effects on adult neurogenesis and granule cell proliferation.

Influence of vestibular input on spatial and nonspatial memory and on hippocampal NMDA receptors.

It has recently been shown that a lack of vestibular sensory information decreases spatial memory performance and induces biochemical changes in the hippocampus in rodents. After vestibular neurectomy, patients display spatial memory deficit and hippocampal atrophy. Our objectives were to explore: (a) spatial (Y maze, radial-arm maze), and non-spatial (object recognition) memory performance, (b) modulation of NMDA receptors within the hippocampus using radioligand binding, and (c) hippocampal atrophy, using MRI, in a rat model of bilateral labyrinthectomy realized in two operations. Chemical vestibular lesions (VLs) were induced in 24 animals by transtympanic injections of sodium arsanilate (30 mg/0.1 ml/ear), one side being lesioned 3 weeks after the other. The control group received transtympanic saline solution (0.1 ml/ear) (n = 24). Spatial memory performance (Y maze and radial maze) decreased after VL. Conversely, non-spatial memory performance (object recognition) was not affected by VL. No hippocampal atrophy was observed with MRI, but density of NMDA receptors were increased in the hippocampus after VL. These findings show that the lack of vestibular information induced specific deficits in spatial memory. Additionally, quantitative autoradiographic data suggest the involvement of the glutamatergic system in spatial memory processes related to vestibular information. When studying spatial memory performances in the presence of vestibular syndrome, two-step labyrinthectomy is a suitable procedure for distinguishing between the roles of the specific components of vestibular input loss and those of impaired locomotor activity.

Rescue of cognitive aging by long-lasting environmental enrichment exposure initiated before median lifespan.

The rescue of cognitive function through environmental enrichment (EE) during aging has been extensively documented. However, the age at onset, the duration of EE, and the cerebral mechanisms required to obtain the greatest benefits still remain to be determined. We have recently shown that EE applied for 3 mo after the median lifespan, i.e., the age at which 50% of the population is still alive (from 17 to 20 mo in NMRI mice), failed to prevent cognitive deficits in senescent animals. In the present study, mice were exposed to EE prior to the median lifespan, and for a longer total duration (from 14 to 20 mo), before the assessment of memory performance and the electrophysiological properties of hippocampal neuronal networks. The EE prevented memory deficits and reduced anxiety as the animal aged. Moreover, EE attenuated the age-related impairment of basal glutamatergic neurotransmission in CA1 hippocampal slices, and reversed the decrease in isolated N-methyl-D-Aspartate receptor (NMDA-R)-dependent synaptic potentials. Surprisingly, EE did not prevent the age-related alteration of theta-burst-induced long-term potentiation (LTP). This study therefore suggests that EE needs to be initiated before the age corresponding to the median lifespan and/or required long duration (> 3 mo) to have an effect on cognitive aging. In addition, we show that EE probably acts through theta-burst-independent mechanisms of synaptic plasticity.

Changes in rat soleus muscle phenotype consecutive to a growth in hypergravity followed by normogravity.

It has been demonstrated that a long-term stay in hypergravity (HG: 2G) modified the phenotype and the contractile properties of rat soleus muscle. The ability of this muscle to contract was drastically reduced, which is a sign of anticipated aging. Consequently, our aim was to determine whether rats conceived, born, and reared in hypergravity showed adaptative capacities in normogravity (NG: 1G). This study was performed on rats divided into two series: the first was reared in HG until 100 days and was submitted to normogravity until 115 to 220 postnatal days (HG-NG rats); the second was made up of age paired groups reared in normogravity (NG rats). The contractile, morphological, and phenotypical properties of soleus muscle were studied. Our results showed that the NG rats were characterized by coexpressions of slow and fast myosin, respectively, 76.5 and 23.5% at 115 days. During their postnatal maturation, the fast isoform was gradually replaced by slow myosin. At 220 days, the relative proportions were respectively 91.05% and 8.95%. From 115 to 220 days, the HG-NG rats expressed 100% of slow myosin isoform and they presented a slower contractile behavior compared with their age-matched groups; at 115 days, the whole muscle contraction time was increased by 35%, and by 15%, at 220 days. Our study underlined the importance of gravity in the muscular development and suggested the existence of critical periods in muscle phenotype installation.

Behavioural consequences of hypergravity in developing rats.

Gravity represents a stable reference for the nervous system. When the individual is increasing in size and weight, gravity may influence several aspects of the sensory and motor developments. To clarify this role, we studied age-dependent modifications of several exteroceptive and proprioceptive reflexes in five groups of rats conceived, born and reared in hypergravity (2 g). Rats were transferred to normal gravity (1 g) at P5 (post-natal day 5), P10, P15, P21, and P27. Aspects of neural development and adaptation to 1 g were assessed until P40. Hypergravity induced a delay in growth and a retardation in the development of contact-righting, air-righting, and negative geotaxis. However, we found an advance in eye opening by about 2-3 days in HG-P5 and HG-P10 rats and an increase in grip-time. No differences were found in tail and grasp reflexes. Our results show that hypergravity leads to a retarded development of motor aspects which are mainly dependent upon the vestibular system.

Kinematics of treadmill locomotion in rats conceived, born, and reared in a hypergravity field (2 g). Adaptation to 1 g.

The kinematics of treadmill locomotion in rats conceived, born, and raised in a hypergravity environment (HG: 2g) until the age of 3 months was investigated for 5 weeks after their exposition to earth's gravity. The locomotor performance of the HG rats (N=7) was compared to that of age-matched control rats (N=8) housed at 1g for the same period. Kinematic analysis of treadmill locomotion was performed up to 35 days of terrestrial life by an optoelectronic motion analyzer (ELITE system). Results showed that the HG rats exhibited a faster locomotor rhythm (increased number of steps/s), walked closer to the ground, and had a more dorsiflexed foot position. Also, HG rats had shorter steps. The data also highlight a fast adaptation to normal gravity since all the locomotor parameters returned to normal values within 3 weeks. The locomotor modifications may be seen as the persistence of a hypergravity-induced posturo-locomotor adaptation in the centrifuge and/or to more functional changes of sensorimotor systems. Because locomotor performance of HG rats is not severely affected, it is concluded that early development of locomotion processes is highly resistant to gravito-inertial changes.

Behavioural changes induced by early and long-term gravito-inertial force modification in the rat.

The study concerns rats conceived, born and raised in a hypergravity environment (HG: 2 g) for 3 months using a centrifuge. They were then exposed to terrestrial gravity (1 g) and submitted to behavioural tests investigating their spontaneous locomotor activity (open-field), their posture (support surface), and their vestibular function (air-righting reflex). Performances were compared to age-matched control rats housed at 1 g for the same time period. Results showed static and dynamic behavioural deficits as early as the rats were exposed to normal gravity. They exhibited strongly increased motor activity in open-field, with longer travelled distances and more scattered trajectories; in addition, the HG rats displayed more numerous rearings than controls did. They showed postural changes characterized by an enlarged support surface and they did not succeed in the air-righting reflex, due to increased time-delay for head righting. None of these changes were permanent. Indeed, for all tests, the HG rats tested after 3 weeks spent in normal terrestrial gravity exhibited behaviours similar to those of the controls. HG-induced changes in the functional properties of the vestibular system may explain the deficits showed by the HG rats once exposed to normal gravity. The adaptation process to 1 g leading to the appearance of normal behaviour takes about 3 weeks. It likely implicates a central re-evaluation of the sensory inputs and an updating of the motor commands.

Contractile properties and myosin expression in rats born and reared in hypergravity.

The effects of hypergravity (HG) on soleus and plantaris muscles were studied in Long Evans rats aged 100 days, born and reared in 2-g conditions (HG group). The morphological and contractile properties and the myosin heavy chain (MHC) content were examined in whole muscles and compared with terrestrial control (Cont) age-paired rats. The growth of HG rats was slowed compared with Cont rats. A decrease in absolute muscle weight was observed. An increase in fiber cross-sectional area/muscle wet weight was demonstrated, associated with an increase in relative maximal tension. The soleus muscle changed into a slower type both in contractile parameters and in MHC content, since HG soleus contained only the MHC I isoform. The HG plantaris muscle presented a faster contractile behavior. Moreover, the diversity of hybrid fiber types expressing multiple MHC isoforms (including MHC IIB and MHC IIX isoforms) was increased in plantaris muscle after HG. Thus the HG environment appears as an important inductor of muscular plasticity both in slow and fast muscle types.

Muscular exercise improves knee position sense in humans.

To determine how position sense depends on the functional state of the receptors involved, we assessed the accuracy of knee position sense before and after a moderate exercise on a cycle ergometer. Measurements were done on 32 healthy subjects with four protocols combining two tasks (intramodal: using the contralateral leg, and crossmodal: using a scheme of a leg on a screen) and two ways of positioning (active and passive). Results showed an improved position sense after exercise with the intramodal protocol combined with active positioning of the reference leg. Whatever the mechanisms involved, enhanced motor performances after exercise can be due not only to improved mechanical properties of the muscles but also to better kinesthetic sensibility.