Social defeat leads to changes in the endocannabinoid system: An overexpression of calreticulin and motor impairment in mice.

Prolonged and sustained stimulation of the hypothalamo-pituitary-adrenal axis have adverse effects on numerous brain regions, including the cerebellum. Motor coordination and motor learning are essential for animal and require the regulation of cerebellar neurons. The G-protein-coupled cannabinoid CB1 receptor coordinates synaptic transmission throughout the CNS and is of highest abundance in the cerebellum. Accordingly, the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired as indicated the righting reflex and the rota-rod. The amount of the endocannabinoid 2-AG increased while CB1 mRNA and protein expression were downregulated after chronic stress. Transcriptome analysis revealed 319 genes differentially expressed by chronic psychosocial stress in the cerebellum; mainly involved in synaptic transmission, transmission of nerve impulse, and cell-cell signaling. Calreticulin was validated as a stress candidate gene. The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice.

Growth hormone treatment attenuates age-related changes in hippocampal short-term plasticity and spatial learning.

Downregulation of the growth hormone/insulin-like growth factor-1 (IGF-1)axis is one of the most robust biomarkers of mammalian aging. Reports have suggested that age-related changes in secretion of growth hormone and IGF-1 contribute to the development of some peripheral characteristics of the aged phenotype including decreased bone density and lean body mass. Recent work has focused on the identification of a role for age-related reductions in growth hormone and IGF-1 in the development of cognitive impairments associated with aging. In the current study, we report that aged (30 month-old) Brown Norway x Fisher rats demonstrate impairments in spatial learning compared with adult (10 month-old) animals, and that 4-month treatment with growth hormone (300 microg twice daily) attenuates age-related learning impairments. After 6 months of treatment, we employed an extracellular paired-pulse protocol to investigate age-related changes in hippocampal short-term plasticity, and found that aged rats exhibit significantly increased paired-pulse ratios (PPRs) at an interpulse interval of 50 ms compared with adult rats. Long-term growth hormone administration restored PPRs in aged animals to values comparable to those observed in adult controls. Since the age-related changes observed in PPR may result from decreases in hippocampal inhibitory tone mediated by GABA(A) receptors, we assessed GABA(A) receptor subunit expression by immunoblot analysis. Data revealed significant age-related decreases in GABA(A) receptor alpha-1 subunit expression which were attenuated by growth hormone treatment. However, hippocampal levels of the gamma2 subunit, glutamic acid decarboxylase (GAD)(65), and GAD(67) protein concentrations were not significantly affected by age or growth hormone treatment. In conclusion, we suggest that age-related decreases in growth hormone and IGF-1 contribute to cognitive decline, in part, via alterations in hippocampal short-term plasticity. Changes in plasticity may reflect a shift in the balance of hippocampal inhibitory and excitatory function.

Suprascapular nerve entrapment caused by supraglenoid cyst compression.

Twenty-two cases of suprascapular nerve entrapment caused by supraglenoid cyst compression were reviewed. Pain and weakness were the presenting symptoms in 14 shoulders and pain alone in 8. Twenty of the cysts were diagnosed by magnetic resonance imaging, and two were confirmed at surgical exploration. Electromyography of 20 shoulders was positive for neurologic involvement for both the infraspinatus and supraspinatus in 4 cases, for the infraspinatus only in 12, and negative in 4. Sixteen shoulders were treated by open excision, arthroscopy, or both. Superior labral lesions were diagnosed in 11 of 12 patients who underwent arthroscopy. At follow-up 10 of the patients who underwent surgery had complete resolution of symptoms, 5 had occasional pain or weakness, and 1 recurrence required a second surgery. Of six patients treated without surgery, two improved and four had no change. Supraglenoid ganglion cysts are common and can easily be diagnosed by magnetic resonance imaging. For patients with symptoms arthroscopy with repair of the superior labral lesion and either arthroscopic debridement or direct open decompression and excision of the cyst is recommended.

Changes in leg volume during microgravity simulation.

Little published information exists regarding the magnitude and time course of cephalad fluid shift resulting from microgravity simulations. Six subjects were exposed to 150 min each at horizontal bed rest, 6 degrees head-down tilt, and horizontal water immersion. Fluid shift was estimated by calculating leg volumes from eight serial girth measurements from groin to ankle before, during, and after exposure. Results were compared with data from the first 3 h of spaceflight. By the end of exposure, total leg volume for the six subjects decreased by 2.6 +/- 0.8%, 1.7 +/- 1.2%, and 4.0 +/- 1.6% for horizontal, head-down, and immersion, respectively. Changes had plateaued for horizontal and head-down and had slowed for immersion. Relatively more fluid was lost from the lower leg than the thigh for all three conditions, particularly head-down. During the first 3 h of spaceflight, total leg volume decreased by 8.6%, and relatively more fluid was lost from the thigh than the lower leg. The difference in volume changes in microgravity and simulated microgravity may be caused by the small transverse pressures still present in ground-based simulations and the extremely nonlinear compliance of tissue.

Gastrointestinal motility in space motion sickness.

Gastrointestinal (Gl) symptoms in space motion sickness (SMS) are significantly different from those in ordinary motion sickness (MS). Vomiting is sudden, often unexpected, infrequent, never prolonged and usually without nausea. Inflight bowel sounds are absent in those with SMS but present after recovery and in those not affected. Recording and tabulation of sounds was the only technique that could be used as a measure of motility during spaceflight operations. There were 17 subjects, 6 unaffected by SMS, who made ambulatory recordings pre- and inflight. With one exception, all those affected had sharply reduced sounds while those unaffected had increases or moderate reductions. The mechanism of vomiting in SMS appears to be secondary to this ileus in contrast to vomiting in ordinary MS, where the emesis center is thought to be directly triggered by the vestibular system. This ileus appears to be the only consistent and reliable indicator for SMS to date.

Fluid shifts in weightlessness.

Studies of leg volumes in space by multiple girth measurements showed reductions of 1.9 L (12.8% of leg volume) with 1.1 L from the non-dominant leg on Skylab 4. On landing, 65% of postflight leg volume increase was complete at 1.5 h. Measurement of the dominant leg during the equivalent period on Shuttle showed a mean loss of 0.9 L which was 90% complete at 150 min. Postflight increases were 87% complete at 1.5 h postlanding. Mass measurements during and after Skylab 4 showed a loss of 2.5 kg over the first 4 d on-orbit with a gain of 2.7 kg over the first 4 d of recovery. These changes are assumed to be tissue fluids secondary to changes in hydrostatic pressures and are much greater than those seen in bed rest. Rate and magnitude of inflight and postflight changes have significant operational impact.

Space shuttle inflight and postflight fluid shifts measured by leg volume changes.

This is a study of the inflight and postflight leg volume changes associated with spaceflight on Space Shuttle missions. The results of this study show an inflight volume loss of 2 L from lower extremities, 1 L from each leg, representing an 11.6% volume change. The vast majority of this change appears to be a shift in body fluids, both intravascular and extravascular. The fluid shift occurs rapidly on Mission Day 1 (MD-1), with it being essentially complete by 6 to 10 h. The regional origin of shift and leg volume change shows a far greater absolute volume (708 ml vs. 318 ml) and percentage (69% vs. 31%) of the total change coming from the thigh as compared to the lower leg. Postflight, the return of fluid to the lower extremities occurs rapidly with the majority of volume return complete within 1.5 h postlanding. At 1 week postflight there is a residual leg volume decrement of 283 ml or 3.2% that is probably due to tissue loss secondary to atrophic deconditioning and weight loss.

Clinical characterization and etiology of space motion sickness.

An inflight, clinically-oriented investigation of SMS was begun on STS-4 and revealed the following: compared to motion sickness on Earth, autonomic signs are significantly different in space motion sickness (SMS) vs. motion sickness (MS) in that sweating is not present, pallor or flushing may be present, and vomiting is episodic, sudden, and brief. Nausea may be present but is more often absent. Onset ranges from minutes to hours, plateaus, and rapidly resolves in 8-72 h with 36 h as average. Postflight reactions have been mild unless deliberately provoked in the early period of re-exposure to gravity. Postflight there is a period of resistance to all forms of motion sickness. There is some evidence for individual reduction in sensitivity on repeated flights. Etiology could not be proven objectively; however, the sensitivity to angular motion, often pronounced in pitch, and theoretical considerations make an intravestibular conflict the most likely cause. Electro-oculogram (EOG), audio-evoked potentials, measurement of fluid shifts, and other studies are inconsistent with a transient vestibular hydrops or increased intracranial pressure as a cause.