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At least 649 records · Page 36
All sourcesNASA NTRSDOE OSTI
NASA NTRS1999

Angiotensin-(1-7) antagonist [D-Ala7-Ang-(1-7);A-779] attenuates post-suspension hypotension in Sprague-Dawley rats

Cardiovascular deconditioning manifested by reduction in mean arterial pressure (MAP) and cardioaccleration are usually observed in astronauts during standing postflight. The head-down tilt (HDT) rat model with "unloaded" hindlimbs has been extensively studied because some of the observed responses mimic observations made during exposure to microgravity. Angiotensin-(1-7) is a biologically active component of the renin-angiotensin system that acts to oppose the pressor and proliferative actions of Angiotensin II. It produces a hypotensive response by either stimulating production of vasodilator prostaglandins (i.e., prostacyclin), increasing nitric oxide or both. In the present study, we have evaluated the role of a specific inhibitor of Ang-(1-7), D-Ala7-Ang-(1-7)[A-779], as a countermeasure against post-suspension hypotension.

Hindlimb Suspension↗
NASA NTRS1996

Histomorphometric study of tibia of rats exposed aboard American Spacelab Life Sciences 2 Shuttle Mission

Tibial bones of rats flown onboard the SLS-2 shuttle mission were studied. Trabecular bone parameters were investigated, including growth plate height, trabecular bone volume, thickness and number, and trabecular separation in the primary and secondary spongiosa. Several histomorphometric changes were noted, allowing researchers to conclude that exposure to microgravity resulted in osteopenia of spongy bone of tibial metaphysis. The roles of bone formation and bone resorption are discussed.

NASA Center ARC↗
NASA NTRS1999

Plasma membrane ordering agent pluronic F-68 (PF-68) reduces neurotransmitter uptake and release and produces learning and memory deficits in rats

A substantial body of evidence indicates that aged-related changes in the fluidity and lipid composition of the plasma membrane contribute to cellular dysfunction in humans and other mammalian species. In the CNS, reductions in neuronal plasma membrane order (PMO) (i.e., increased plasma membrane fluidity) have been attributed to age as well as the presence of the beta-amyloid peptide-25-35, known to play an important role in the neuropathology of Alzheimer's disease (AD). These PMO increases may influence neurotransmitter synthesis, receptor binding, and second messenger systems as well as signal transduction pathways. The effects of neuronal PMO on learning and memory processes have not been adequately investigated, however. Based on the hypothesis that an increase in PMO may alter a number of aspects of synaptic transmission, we investigated several neurochemical and behavioral effects of the membrane ordering agent, PF-68. In cell culture, PF-68 (nmoles/mg SDS extractable protein) reduced [3H]norepinephrine (NE) uptake into differentiated PC-12 cells as well as reduced nicotine stimulated [3H]NE release. The compound (800-2400 microg/kg, i.p., resulting in nmoles/mg SDS extractable protein in the brain) decreased step-through latencies and increased the frequencies of crossing into the unsafe side of the chamber in inhibitory avoidance training. In the Morris water maze, PF-68 increased the latencies and swim distances required to locate a hidden platform and reduced the time spent and distance swam in the previous target quadrant during transfer (probe) trials. PF-68 did not impair performance of a well-learned working memory task, the rat delayed stimulus discrimination task (DSDT), however. Studies with 14C-labeled PF-68 indicated that significant (pmoles/mg wet tissue) levels of the compound entered the brain from peripheral (i.p.) injection. No PF-68 related changes were observed in swim speeds or in visual acuity tests in water maze experiments, rotorod performance, or in tests of general locomotor activity. Furthermore, latencies to select a lever in the DSDT were not affected. These results suggest that PF-68 induced deficits in learning and memory without confounding peripheral motor, sensory, or motivational effects at the tested doses. Furthermore, none of the doses induced a conditioned taste aversion to a novel 0.1% saccharin solution indicating a lack of nausea or gastrointestinal malaise induced by the compound. The data indicate that increases in neuronal plasma membrane order may have significant effects on neurotransmitter function as well as learning and memory processes. Furthermore, compounds such as PF-68 may also offer novel tools for studying the role of neuronal PMO in mnemonic processes and changes in PMO resulting from age-related disorders such as AD.

Poloxamer/pharmacology↗
NASA NTRS2000

Physiological response of rats to delivery of helium and xenon: implications for hyperpolarized noble gas imaging

The physiological effects of various hyperpolarized helium and xenon MRI-compatible breathing protocols were investigated in 17 Sprague-Dawley rats, by continuous monitoring of blood oxygen saturation, heart rate, EKG, temperature and endotracheal pressure. The protocols included alternating breaths of pure noble gas and oxygen, continuous breaths of pure noble gas, breath-holds of pure noble gas for varying durations, and helium breath-holds preceded by two helium rinses. Alternate-breath protocols up to 128 breaths caused a decrease in oxygen saturation level of less than 5% for either helium or xenon, whereas 16 continuous-breaths caused a 31.5% +/- 2.3% decrease in oxygen saturation for helium and a 30.7% +/- 1. 3% decrease for xenon. Breath-hold protocols up to 25 s did not cause the oxygen saturation to fall below 90% for either of the noble gases. Oxygen saturation values below 90% are considered pathological. At 30 s of breath-hold, the blood oxygen saturation dropped precipitously to 82% +/- 0.6% for helium, and to 76.5% +/- 7. 4% for xenon. Breath-holds longer than 10 s preceded by pre-rinses caused oxygen saturation to drop below 90%. These findings demonstrate the need for standardized noble gas inhalation procedures that have been carefully tested, and for continuous physiological monitoring to ensure the safety of the subject. We find short breath-hold and alternate-breath protocols to be safe procedures for use in hyperpolarized noble gas MRI experiments. Copyright 2000 John Wiley & Sons, Ltd.

NASA Discipline Life Sciences Technologies↗
NASA NTRS2000

Effect of hyperosmotic solutions on salt excretion and thirst in rats

We investigated urinary changes and thirst induced by infusion of hyperosmotic solutions in freely moving rats. Intracarotid infusions of 0.3 M NaCl (4 ml/20 min, split between both internal carotid arteries) caused a larger increase in excretion of Na(+) and K(+) than intravenous infusions, indicating that cephalic sensors were involved in the response to intracarotid infusions. Intravenous and intracarotid infusions of hyperosmotic glycerol or urea (300 mM in 150 mM NaCl) had little or no effect, suggesting the sensors were outside the blood-brain barrier (BBB). Intracarotid infusion of hypertonic mannitol (300 mM in 150 mM NaCl) was more effective than intravenous infusion, suggesting that cell volume rather than Na(+) concentration of the blood was critical. Similarly, intracarotid infusion (2 ml/20 min, split between both sides), but not intravenous infusion of hypertonic NaCl or mannitol caused thirst. Hyperosmotic glycerol, infused intravenously or into the carotid arteries, did not cause thirst. We conclude that both thirst and electrolyte excretion depend on a cell volume sensor that is located in the head, but outside the BBB.

NASA Discipline Regulatory Physiology↗
NASA NTRS1999

Incomplete segregation of endorgan-specific vestibular ganglion cells in mice and rats

The endorgan-specific distribution of vestibular ganglion cells was studied in neonatal and postnatal rats and mice using indocarbocyanine dye (DiI) and dextran amines for retrograde and anterograde labeling. Retrograde DiI tracing from the anterior vertical canal labeled neurons scattered throughout the whole superior vestibular ganglion, with denser labeling at the dorsal and central regions. Horizontal canal neurons were scattered along the dorsoventral axis with more clustering toward the dorsal and ventral poles of this axis. Utricular ganglion cells occupied predominantly the central region of the superior vestibular ganglion. This utricular population overlapped with both the anterior vertical and horizontal canals' ganglion cells. Posterior vertical canal neurons were clustered in the posterior part of the inferior vestibular ganglion. The saccular neurons were distributed in the two parts of the vestibular ganglion, the superior and inferior ganglia. Within the inferior ganglion, the saccular neurons were clustered in the anterior part. In the superior ganglion, the saccular neurons were widely scattered throughout the whole ganglion with more numerous neurons at the posterior half. Small and large neurons were labeled from all endorgans. Examination of the fiber trajectory within the superior division of the vestibular nerve showed no clear lamination of the fibers innervating the different endorgans. These results demonstrate an overlapping pattern between the different populations within the superior ganglion, while in the inferior ganglion, the posterior canal and saccular neurons show tighter clustering but incomplete segregation. This distribution implies that the ganglion cells are assigned for their target during development in a stochastic rather than topographical fashion.

NASA Discipline Developmental Biology↗
NASA NTRS1999

Cloning the promoter for transforming growth factor-beta type III receptor. Basal and conditional expression in fetal rat osteoblasts

Transforming growth factor-beta binds to three high affinity cell surface molecules that directly or indirectly regulate its biological effects. The type III receptor (TRIII) is a proteoglycan that lacks significant intracellular signaling or enzymatic motifs but may facilitate transforming growth factor-beta binding to other receptors, stabilize multimeric receptor complexes, or segregate growth factor from activating receptors. Because various agents or events that regulate osteoblast function rapidly modulate TRIII expression, we cloned the 5' region of the rat TRIII gene to assess possible control elements. DNA fragments from this region directed high reporter gene expression in osteoblasts. Sequencing showed no consensus TATA or CCAAT boxes, whereas several nuclear factors binding sequences within the 3' region of the promoter co-mapped with multiple transcription initiation sites, DNase I footprints, gel mobility shift analysis, or loss of activity by deletion or mutation. An upstream enhancer was evident 5' proximal to nucleotide -979, and a silencer region occurred between nucleotides -2014 and -2194. Glucocorticoid sensitivity mapped between nucleotides -687 and -253, whereas bone morphogenetic protein 2 sensitivity co-mapped within the silencer region. Thus, the TRIII promoter contains cooperative basal elements and dispersed growth factor- and hormone-sensitive regulatory regions that can control TRIII expression by osteoblasts.

Non-NASA Center↗
NASA NTRS1998

Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

NASA Discipline Musculoskeletal↗
NASA NTRS1998

Multiple receptor subtypes mediate the effects of serotonin on rat subfornical organ neurons

The subfornical organ (SFO) receives significant serotonergic innervation. However, few reports have examined the functional effects of serotonin on SFO neurons. This study characterized the effects of serotonin on spontaneously firing SFO neurons in the rat brain slice. Of 31 neurons tested, 80% responded to serotonin (1-100 microM) with either an increase (n = 15) or decrease (n = 10) in spontaneous activity. Responses to serotonin were dose dependent and persisted after synaptic blockade. Excitatory responses could also be mimicked by the 5-hydroxytryptamine (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI; 1-10 microM) and could be blocked by the 5-HT2A/2C-receptor antagonist LY-53,857 (10 microM). LY-53,857 unmasked inhibitory responses to serotonin in 56% of serotonin-excited cells tested. Serotonin-inhibited cells were also inhibited by the 5-HT1A-receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT; 1-10 microM; n = 7). The data indicate that SFO neurons are responsive to serotonin via postsynaptic activation of multiple receptor subtypes. The results suggest that excitatory responses to serotonin are mediated by 5-HT2A or 5-HT2C receptors and that inhibitory responses may be mediated by 5-HT1A receptors. In addition, similar percentages of serotonin-excited and -inhibited cells were also sensitive to ANG II. As such the functional relationship between serotonin and ANG II in the SFO remains unclear.

Non-NASA Center↗
NASA NTRS1998

Non-NMDA receptor antagonist-induced drinking in rat

Glutamate has been implicated in the central control of mechanisms that maintain body fluid homeostasis. The present studies demonstrate that intracerebroventricular (i.c.v.) injections of the non-N-methyl-d-aspartate (NMDA) receptor antagonists 6, 7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) induce drinking in rats. The dipsogenic effect of i.c.v. DNQX was antagonized by the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). The water intake induced by DNQX was also blocked by pretreatment with a NMDA receptor antagonist, MK-801, but not by angiotensin type 1 (AT1) or acetylcholine muscarinic receptor antagonists (losartan and atropine). The results indicate that non-NMDA receptors may exert a tonic inhibitory effect within brain circuits that control dipsogenic activity and that functional integrity of NMDA receptors may be required for the non-NMDA receptor antagonists to induce water intake. Copyright 1998 Published by Elsevier Science B.V.

Non-NASA Center↗
NASA NTRS1997

Effect of atrophy and contractions on myogenin mRNA concentration in chick and rat myoblast omega muscle cells

The skeletal rat myoblast omega (RMo) cell line forms myotubes that exhibit spontaneous contractions under appropriate conditions in culture. We examined if the RMo cells would provide a model for studying atrophy and muscle contraction. To better understand how to obtain contractile cultures, we examined levels of contraction under different growing conditions. The proliferation medium and density of plating affected the subsequent proportion of spontaneously contracting myotubes. Using a ribonuclease protection assay, we found that exponentially growing RMo myoblasts contained no detectable myogenin or herculin mRNA, while differentiating myoblasts contained high levels of myogenin mRNA but no herculin mRNA. There was no increase in myogenin mRNA concentration in either primary chick or RMo myotubes whose contractions were inhibited by depolarizing concentrations of potassium (K+). Thus, altered myogenin mRNA concentrations are not involved in atrophy of chick myotubes. Depolarizing concentrations of potassium inhibited spontaneous contractions in both RMo cultures and primary chick myotube cultures. However, we found that the myosin concentration of 6-d-old contracting RMo cells fed medium plus AraC was 11 +/- 3 micrograms myosin/microgram DNA, not significantly different from 12 +/- 4 micrograms myosin/microgram DNA (n = 3), the myosin concentration of noncontracting RMo cells (treated with 12 mM K+ for 6 d). Resolving how RMo cells maintained their myosin content when contraction is inhibited may be important for understanding atrophy.

Muscular Atrophy↗
NASA NTRS1998

Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats

Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81: 2509-2516, 1996). In that study, the increase in IGF-I was found to precede measurable increases in muscle protein and was correlated with an increase in muscle DNA content. The present study was undertaken to test the hypothesis that direct IGF-I infusion would result in an increase in muscle DNA as well as in various measurements of muscle size. Either 0.9% saline or nonsystemic doses of IGF-I were infused directly into a non-weight-bearing muscle of rats, the tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. Saline infusion had no effect on the mass, protein content, or DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart weight. The absolute weight of the infused TA muscles was approximately 9% greater (P < 0.05) than that of the contralateral TA muscles. IGF-I infusion resulted in significant increases in the total protein and DNA content of TA muscles (P < 0.05). As a result of these coordinated changes, the DNA-to-protein ratio of the hypertrophied TA was similar to that of the contralateral muscles. These results suggest that IGF-I may be acting to directly stimulate processes such as protein synthesis and satellite cell proliferation, which result in skeletal muscle hypertrophy.

Non-NASA Center↗
NASA NTRS1998

Synaptic changes in rat maculae in space and medical imaging: the link

Two different space life sciences missions (SLS-1 and SLS-2) have demonstrated that the synapses of the hair cells of rat vestibular maculae increase significantly in microgravity. The results also indicate that macular synapses are sensitive to stress. These findings argue that vestibular maculae exhibit neuroplasticity to macroenvironmental and microenvironmental changes. This capability should be clinically relevant to rehabilitative training and/or pharmacological treatments for vestibular disease. The results of this ultrastructural research also demonstrated that type I and type II hair cells are integrated into the same neuronal circuitry. The findings were the basis for development of three-dimensional reconstruction software to learn details of macular wiring. This software, produced for scientific research, has now been adapted to reconstruct the face and skull directly from computerized tomography scans. In collaboration with craniofacial reconstructive surgeons at Stanford University Medical Center, an effort is under way to produce a virtual environment workbench for complex craniofacial surgery. When completed, the workbench will help surgeons train for and simulate surgery. The methods are patient specific. This research illustrates the value of basic research in leading to unanticipated medical applications.

Flight Experiment↗
NASA NTRS1997

Mechanisms for vasopressin effects on intraocular pressure in anesthetized rats

Continuous intracameral infusions of a balanced salt solution (0.175 microliter min-1) have been reported to raise intraocular pressure (IOP) in anesthetized rats. Palm et al. (1995) previously reported that this effect was attenuated significantly by inclusion of arginine-vasopressin (AVP, 10 ng 0.175 microliter-1) in the infusate. This study used experimental and computer simulation methods to investigate factors underlying these changes in IOP. First, constant intracameral infusions of artificial cerebrospinal fluid (aCSF) at different fixed rates (0.049-0.35 microliter min-1) were used to estimate the outflow resistance. Secondly, IOP responses were measured during an 2 hr intracameral infusion of either aCSF or AVP that was the sum of a small constant component (0.05 microliter min-1) and a larger periodic component (0.25 microliter min-1, cycling for 4 min on, then 4 min off); the mean infusion rate was 0.175 microliter min-1. As shown previously for 0.175 microliter min-1 constant infusions, the periodic aCSF infusion induced a significant rise in IOP that was attenuated by AVP administration. Complex demodulation analysis and the estimated gain parameter of a second order transfer function fit to the periodic responses indicated that outflow resistance increased significantly during the infusions in both aCSF and AVP groups, but that the indices of resistance did not differ significantly between aCSF and AVP infused eyes. This finding implies that changes in outflow resistance do not explain the difference in IOP responses to intracameral aCSF and AVP. The two responses differed significantly, though, in damping factors, such that the aCSF responses were considerably more underdamped than the AVP responses. It is hypothesized that aCSF-induced increase in IOP reflects both (1) a small component reflecting increased outflow resistance and (2) a larger non-resistive component. Since the non-resistive component is insensitive to pretreatment with acetazolamide, it is suggested that the aCSF-induced elevation in IOP reflects primarily vascular perfusion changes that are reduced by local vasoconstrictor actions of AVP. The latter mechanism likely maintains vascular perfusion of the globe when intraocular hypertension develops.

NASA Discipline Cardiopulmonary↗
NASA NTRS1997

Dietary calcium attenuates platelet aggregation and intracellular Ca2+ mobilization in spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) are known to be blood pressure sensitive to dietary calcium. The effects of dietary calcium on platelet aggregation and intracellular Ca2+ mobilization were assessed by turbidimetric methods and fura-2 methods, respectively, in washed platelets of SHR. Ca2+ ATPase activity was examined in aortic membrane fractions. Six weeks of dietary calcium supplementation attenuated the increase of systolic blood pressure (SBP 199 +/- 16 v 170 +/- 9 mm Hg, P < .001) and thrombin-induced platelet aggregation (84.5 +/- 3.7 v 73.7 +/- 7.4%, P < .004) at 9 weeks of age. The ionomycin-induced intracellular calcium ([Ca2+]i) peak in the absence of external Ca2+, which reflects [Ca2+]i storage size, and thrombin-evoked [Ca2+]i release from [Ca2+]i storage were decreased by 2.0% Ca diet (472 +/- 55 v 370 +/- 23 nmol/L, P < .001, 339 +/- 29 v 278 +/- 33 nmol/L, P < .002). In addition, SBP was positively correlated with platelet aggregation (r = 0.703, P = .0088), thrombin-evoked [Ca2+]i (r = 0.739, P = .0044), and ionomycin-induced [Ca2+]i (r = 0.591, P = .0415), respectively. However, there was no significant effect of dietary calcium on Ca2+-ATPase activity in aortic membranes. These results suggest that dietary calcium supplementation had a beneficial effect on platelets of SHR by attenuating [Ca2+]i mobilization from [Ca2+]i storage. The hypotensive effect of dietary calcium might be associated with attenuated [Ca2+]i mobilization in SHR.

NASA Discipline Regulatory Physiology↗
NASA NTRS1997

Effects of growth hormone and low dose estrogen on bone growth and turnover in long bones of hypophysectomized rats

Pituitary hormones are recognized as critical to longitudinal growth, but their role in the radial growth of bone and in maintaining cancellous bone balance are less clear. This investigation examines the histomorphometric effects of hypophysectomy (Hx) and ovariectomy (OVX) and the subsequent replacement of growth hormone (GH) and estrogen (E), in order to determine the effects and possible interactions between these two hormones on cortical and cancellous bone growth and turnover. The replacement of estrogen is of interest since Hx results in both pituitary and gonadal hormone insufficiencies, with the latter being caused by the Hx-associated reduction in follicle stimulating hormone (FSH). All hypophysectomized animals received daily supplements of hydrocortisone (500 microg/kg) and L-thyroxine (10 microg/kg), whereas intact animals received daily saline injections. One week following surgery, hypophysectomized animals received either daily injections of low-dose 17 beta-estradiol (4.8 microg/kg s.c.), 3 X/d recombinant human GH (2 U/kg s.c.), both, or saline for a period of two weeks. Flurochromes were administered at weekly intervals to label bone matrix undergoing mineralization. Whereas Hx resulted in reductions in body weight, uterine weight, and tibial length, OVX significantly increased body weight and tibial length, while reducing uterine weight. The combination of OVX and Hx resulted in values similar to Hx alone. Treatment with GH normalized body weight and bone length, while not affecting uterine weight in hypophysectomized animals. Estrogen increased uterine weight, while not impacting longitudinal bone growth and reduced body weight. Hypophysectomy diminished tibial cortical bone area through reductions in both mineral appositional rate (MAR) and bone formation rate (BFR). While E had no effect, GH increased both MAR and BFR, though not to sham-operated (control) levels. Hypophysectomy reduced proximal tibial trabecular number and cancellous bone area, and increased trabecular separation. Both GH and E reduced cancellous osteopenia, although employing different mechanisms. GH reduced the decrease in trabecular thickness, whereas E reduced the decrease in trabecular number and the increase in trabecular separation. Hypophysectomy reduced both Tb.MAR and Tb.BFR while treatment with GH enhanced them. This investigation has shown that Hx and GH have a dramatic impact on selected static and dynamic indices of rat cortical and cancellous histomorphometry. Furthermore, the mechanisms of action of GH and E differ, and suggest that some of the skeletal changes associated with Hx are caused by deficiencies in estrogen as well as deficiencies in growth hormone.

NASA Discipline Regulatory Physiology↗
NASA NTRS1997

Morphological evidence for local microcircuits in rat vestibular maculae

Previous studies suggested that intramacular, unmyelinated segments of vestibular afferent nerve fibers and their large afferent endings (calyces) on type I hair cells branch. Many of the branches (processes) contain vesicles and are presynaptic to type II hair cells, other processes, intramacular nerve fibers, and calyces. This study used serial section transmission electron microscopy and three-dimensional reconstruction methods to document the origins and distributions of presynaptic processes of afferents in the medial part of the adult rat utricular macula. The ultrastructural research focused on presynaptic processes whose origin and termination could be observed in a single micrograph. Results showed that calyces had 1) vesiculated, spine-like processes that invaginated type I cells and 2) other, elongate processes that ended on type II cells pre- as well as postsynaptically. Intramacular, unmyelinated segments of afferent nerve fibers gave origin to branches that were presynaptic to type II cells, calyces, calyceal processes, and other nerve fibers in the macula. Synapses with type II cells occurred opposite subsynaptic cisternae (C synapses); all other synapses were asymmetric. Vesicles were pleomorphic but were differentially distributed according to process origin. Small, clear-centered vesicles, approximately 40-60 nm in diameter, predominated in processes originating from afferent nerve fibers and basal parts of calyces. Larger vesicles approximately 70-120 nm in diameter having approximately 40-80 nm electron-opaque cores were dominant in processes originating from the necks of calyces. Results are interpreted to indicate the existence of a complex system of intrinsic feedforward (postsynaptic)-feedback (presynaptic) connections in a network of direct and local microcircuits. The morphological findings support the concept that maculae dynamically preprocess linear acceleratory information before its transmission to the central nervous system.

NASA Center ARC↗
NASA NTRS1997

Alteration of mineral crystallinity and collagen cross-linking of bones in osteopetrotic toothless (tl/tl) rats and their improvement after treatment with colony stimulating factor-1

A common feature of various types of mammalian osteopetroses is a marked increase in bone mass accompanied by spontaneous bone fractures. The toothless (tl/tl) rat osteopetrotic mutation is characterized by drastically reduced bone resorption due to a profound deficiency of osteoclasts and their precursors. An altered bone morphology has also been observed. The mutants cannot be cured by bone marrow transplantation, but skeletal defects are greatly reduced after treatment with colony stimulating factor 1 (CSF-1). The objectives of this study were to characterize mineral and collagen matrices in cancellous and compact bone isolated from long bones of 6-week-old normal littermates, tl/tl osteopetrotic mutants and mutants (tl/tl) treated with CSF-1. There were no differences in bone mineral content, but a significant decrease in the crystallinity of mineral evaluated by the method based on electron paramagnetic resonance spectrometry was observed in all bones of tl/tl mutants as compared to that of controls. Within the collagen matrix, slight decreases in the labile cross-links, but significant increases in the content of the stable cross-links, pyridinoline, and deoxypyridinoline, were observed in both cancellous and compact bone of osteopetrotic mutants. In tl/tl mutants treated with human recombinant CSF-1, the normalization of the crystallinity of bone mineral as well as collagen cross-links was found. Our results indicate that remodeling of bone matrix in tl/tl mutants is highly suppressed, but that after treatment with CSF-1, this activity recovers significantly. Taken together, these data provide further support for the hypothesis that CSF-1 is an essential factor for normal osteoclast differentiation and bone remodelling.

NASA Discipline Musculoskeletal↗