Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diazepam was administered to gravid rat dams on days 13 through 20 of gestation, at either 1 or 5 mg/kg/day. Pups were observed on several behavioral paradigms throughout the preweaning period. The high dose resulted in a failure to maintain weight gain at the same rate as controls. Additionally, this dose produced a deficit in the ability of 8-day-old pups to autonomically thermoregulate. Female littermates of these pups displayed altered habituation behavior on a holeboard apparatus when tested on postnatal day 12 (PN 12). The low dose attenuated the normal drop in body temperature produced by removal of the pup from its home cage on PN8. This dose also slightly decreased responding on a photocell activity task on PN15. Neither dose was found to affect muscle strength, as measured by hang time. The results suggest that the postnatal effects of prenatal diazepam exposure are dose-specific, in that low dose treatment leads to a different type of behavioral consequence than does exposure to higher doses.
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PMID:Behavioral consequences of prenatal diazepam exposure in rats. 666 14

The retinoic acid induced 1 (RAI1) gene when deleted or mutated results in Smith-Magenis syndrome (SMS), while duplication of 17p11.2, including RAI1, results in the dup(17)(p11.2) syndrome characterized by mental retardation, growth and developmental delays, and hyperactivity. Mouse models for these human syndromes may help define critical roles for RAI1 in mammalian development and homeostasis that otherwise cannot be deduced from patient studies. A mouse model for duplication, Dp(11)17+, involving Rai1 has been reported. However, this mutant was engineered on a mixed genetic background confounding phenotypic effects due to possible modifier genes. We have therefore created and evaluated mice with a graded series of four (hemizygous) and six (homozygous) copies of Rai1, and overexpressing Rai1>1.5-fold and >2-fold, respectively. Data show that Rai1-transgenic mice have growth retardation, increased locomotor activity, and abnormal anxiety-related behavior compared to wild-type littermates. Rai1-transgenic mice also have an altered gait with short strides and long sways, impaired ability on a cage-top hang test, decreased forelimb grip strength, and a dominant social behavior. Further, analyses of homozygous transgenic mice revealed a dosage-dependent exacerbation of the phenotype, including extreme growth retardation, severe neurological deficits, and increased hyperactivity. Our results show that Rai1 dosage has major consequences on molecular processes involved in growth, development, and neurological and behavioral functions, thus providing evidence for several dosage-thresholds for phenotypic manifestations causing dup(17)(p11.2) syndrome or SMS in humans.
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PMID:How much is too much? Phenotypic consequences of Rai1 overexpression in mice. 1828 28

Treatment with N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine (KET) or phencyclidine (PCP), can trigger apoptotic neurodegeneration in neonatal rodents; however, little is known about the behavioral alterations resulting from such treatment. Here, rats were sc treated with saline; 10 mg/kg PCP on postnatal days (PNDs) 7, 9, and 11; 20 mg/kg KET (six injections every 2 h on PND 7); or a regimen of ketamine and 250 mg/kg L-carnitine (KLC) both administered on PND 7 with additional 250 mg/kg doses of L-carnitine given on PNDs 8-11. Postinjection, the home cage behavior of each pup was categorized on PNDs 7-11. Slant board and forelimb hang behaviors were examined on PNDs 8-11 and 12-16, respectively. The initial KET or KLC injections on PND 7 elevated abnormal home cage activity (i.e., paresis and paddling); however, KLC pup behavior returned to normal by the fourth injection, indicating the protective effects of L-carnitine against NMDA antagonist toxicity. PCP treatment caused substantial abnormal home cage activity on each injection day (PNDs 7, 9, and 11). Latencies to turn on the slant board were significantly longer on PND 8 for KET- and PCP-treated pups and PND 10 for PCP-treated pups. On PND 12, the forelimb hang time of PCP-treated pups was significantly shorter. Body weight was decreased on PNDs 8-18 in PCP-treated pups and PNDs 8-10 in KET-treated pups. These data indicate that developmental NMDA antagonist treatment causes short-term behavioral alterations which appear related to motor coordination and may be cerebellar in nature. Furthermore, single PCP injections appear more potent at altering behavior than multiple injections of KET.
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PMID:Neonatal PCP is more potent than ketamine at modifying preweaning behaviors of Sprague-Dawley rats. 1866 23

Glutamate activation of the NMDA receptor is essential for neuronal differentiation, migration, and survival. Treatment with NMDA receptor antagonists, such as ketamine (KET) or phencyclidine (PCP), can trigger apoptosis in neonatal rats. However, L-carnitine (LC) treatment appears to prevent glutamate-induced toxicity in the developing CNS. Previously, we described altered preweaning behaviors (i.e., abnormal home cage, slant board and forelimb hang behaviors) resulting from neonatal PCP and KET treatment. Those adverse effects of KET were somewhat ameliorated by LC [Boctor SY, Wang C, Ferguson SA. Neonatal PCP is more potent than ketamine at modifying preweaning behaviors of Sprague-Dawley rats. Toxicol Sci 2008;106:172-9]. Here, a portion of those subjects were evaluated for prepulse inhibition (PPI) of the acoustic startle response at postnatal day (PND) 25 since previous reports described PCP-induced effects on this response. Rats were subcutaneously treated with: saline; 10 mg/kg PCP (1x/day) on PNDs 7, 9 and 11; 20 mg/kg KET (6 injections every 2h on PND 7); or a similar regimen of ketamine and 250 mg/kg LC on PND 7, with a single injection of 250 mg/kg LC on PNDs 8-11 (KLC). Male and female rats were assessed using a standard PPI paradigm with prepulses of 68, 78 and 82 dB. Body weight was decreased 17-21% and whole brain weight was decreased 10% in PCP-treated rats. Specifically, cerebellar weight was significantly less in PCP-treated rats relative to control. Despite the magnitude of those PCP-induced changes, startle response in normal pulse only trials and percent of PPI in PCP-, KET-, and KLC-treated groups were comparable to controls. Average latency to maximum startle was 2.6 ms less in females than males (p<0.007); there were no other significant sex effects. The lack of neonatal PCP treatment on later PPI is similar to that reported by Rasmussen et al. [Rasmussen BA, O'Neil J, Manaye KF, Perry DC, Tizabi Y. Long-term effects of developmental PCP administration on sensorimotor gating in male and female rats. Psychopharmacology (Berl) 2007; 190: 43-9.], and indicates that neonatal PCP-induced effects on PPI [Wang C, McInnis J, Ross-Sanchez M, Shinnick-Gallagher P, Wiley JL, Johnson KM. Long-term behavioral and neurodegenerative effects of perinatal phencyclidine administration: implications for schizophrenia. Neuroscience 2001; 107: 535-50.] appear difficult to replicate.
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PMID:Neonatal NMDA receptor antagonist treatments have no effects on prepulse inhibition of postnatal day 25 Sprague-Dawley rats. 1903 86

Neonatal ketamine (KET) or phencyclidine (PCP) treatment can trigger apoptotic neurodegeneration in rodents. Previously, we described KET- and PCP-induced altered body weight and home cage, slant board and forelimb hang behaviors in preweaning rats (Boctor et al., 2008). In that study, L-carnitine (LC) attenuated the KET-induced behavioral alterations and body weight decrements. The four subcutaneous (sc) treatment groups were: (1) saline; (2) 10 mg/kg PCP on PNDs 7, 9 and 11; (3) 20 mg/kg KET (6 injections; one every 2h on PND 7); or (4) a regimen of KET and 250 mg/kg LC (KLC) both administered on PND 7, with additional 250 mg/kg doses of LC on PNDs 8-11. A portion of each treatment group was evaluated for postweaning behaviors which included grip strength and motor coordination (postnatal days (PNDs) 22 or 71), locomotor sensitization (PND 42), spatial alternation (PNDs 22-70) and residential running wheel activity (PNDs 72-77). On PND 42 or 78, whole and regional brain weights were measured. Grip strength and motor coordination were unaffected at either age by neonatal treatment. On PND 42, neonatally treated KET- or KLC-treated rats responded to a challenge of 5mg/kg KET with activity similar to controls that received the same challenge. Neonatal PCP treatment, however, induced significant sensitization to a challenge of 3mg/kg PCP on PND 42 relative to controls that received the same challenge, causing increased activity which was especially profound in females. Performance on a continuous spatial alternation task requiring a "win-shift, lose-stay" strategy appeared unaffected by neonatal KET or KLC treatment. PCP treatment, however, caused significantly increased random responding and shorter choice latencies. In addition, neonatal PCP treatment elevated light and dark period running wheel activity and reduced PND 42 and 78 body and whole brain weights. These findings provide further evidence that PCP treatment on PNDs 7, 9, and 11 causes subtle cognitive deficits and long-term alterations in activity that are unrelated to deficits in grip strength or motor coordination. Further, repeated KET treatment on PND 7 does not appear to result in severe behavioral modifications.
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PMID:Altered adult locomotor activity in rats from phencyclidine treatment on postnatal days 7, 9 and 11, but not repeated ketamine treatment on postnatal day 7. 1985 22

It will be seen at once that the mean values obtained for calcium are higher than most of those recorded in the literature, and that the values for inorganic phosphorus are perhaps lower. It is well to bear in mind, however, that the significance that may be attached to any series of determinations of calcium and inorganic phosphorus in the blood of animals depends largely upon the conditions under which the determinations are made. As is well known, there are many factors that may affect the values obtained, including inherent differences in the animal material and the method of analysis used as well as the particular procedure employed in carrying out a given method. When all other conditions are uniform, irregularities in the handling of the blood after it is drawn will give rise to surprisingly large differences in the results for both calcium and inorganic phosphorus, as permitting blood to stand tends to decrease calcium values and to increase those for inorganic phosphorus. It seems desirable, therefore, to emphasize the fact that the results recorded above are to be viewed as results obtained under certain definitely prescribed conditions which differ in several important respects from those governing determinations made by other workers in this field. Moreover, it is to be noted that the conditions varied to some extent with each of the 4 groups of animals comprising this series. For example, there was a small but definite age difference. The animals of Groups I and II were older and more mature than those of Groups III and IV at the beginning of the experiments, and this initial difference was increased by the extension of the experiments on Groups I and II over a longer period of time, so that the observations made on these animals not only included data for a more advanced age, but represented a mean age considerably above that of the observations made on the animals of Groups III and IV. There was a similar difference of experimental conditions between Groups III and IV, while the observations on Group II differed from those on Group I in that no blood analyses were made on the animals of Group II for 2 months after they were placed under observation. These particular features of the experiments are mentioned because an examination of the text-figures will show that a line of cleavage between Groups I and II on the one hand, and III and IV on the other, is traceable through all of the distribution curves and to some extent in the tabulated results. With the combined values as the axis of distribution, Groups I and II invariably hang together, or swing to one side, while Groups III and IV swing to the other. Moreover, the extreme positions are usually represented by Groups II and IV. Whether these peculiarities of the results are in reality attributable to the conditions mentioned or to some other cause, such as the length of cage life (2), or the particular period covered by the observations, the suggested relation is sufficient to indicate the extent to which even slight differences in experimental conditions may affect the results obtained for blood calcium and inorganic phosphorus. The values obtained for calcium may be regarded as showing a fairly close agreement (Tables I and II and Text-fig. 1). The extreme difference between the means for the 4 groups of animals is only 0.5 mg. or approximately 3.00 per cent of the mean for the combined groups. Still, the small absolute difference between the means for Groups I and IV is nearly 6 times its probable error and, hence, cannot be disregarded. The most important feature of these results is, however, the range of normal variation. The distribution curves (Text-fig. 1) show a remarkably close agreement in the frequency with which values of a given magnitude occurred and an unusually symmetrical distribution of all values. The coefficients of variation are comparatively small (7.09 to 8.9 per cent), but values anywhere between 14.0 and 16.0 mg. of calcium per 100 cc. of serum occurred with great frequency, while figures as low as 13.5 or as high as 17.5 mg. (Table II) were by no means rare; and the extreme limits of observation indicate a potential difference in the calcium content of the blood of normal rabbits of as much as 100 per cent. Inorganic phosphorus was found to be subject to much wider variation than calcium (Tables III and IV and Text-fig. 2). The coefficient of variation is approximately twice that for calcium (17.29 and 8.01 respectively), while the group means for phosphorus show a difference of 0.85 mg. per 100 cc. of serum. This difference is small in absolute value, but is nearly 20.0 per cent of the mean for all groups and is 15 times its probable error. It is safe to assume, therefore, that the values obtained indicate an actual difference in the inorganic phosphorus in the blood of the several groups of animals. This conclusion is borne out by the distribution frequencies (Table IV and Text-fig. 2) which show that the values obtained for Groups I and II lie at a distinctly lower level than those for Groups III and IV; the difference between modal classes is, in fact, of the same order as that shown by the means. The limits of probable variation as determined by the standard deviation of the combined results are 3.73 and 5.29 mg. per 100 cc. of serum, but one-third of all values lie outside of these limits, while the extreme limits of normal are sufficiently wide to include values that may differ by as much as 200.0 or even 300.0 per cent. From the values obtained for calcium and inorganic phosphorus, the relation existing between the two substances may be measured in a number of ways. The ratio of the calcium to the phosphorus and the product of the amounts of the two substances have received the greatest attention. In addition to these values, we have computed values for the sum and for the ratio of the product to the sum, and also for the sum of the calcium-phophorus ratio and the product-sum ratio. The value for the sum of the calcium and inorganic phosphorus in the serum is determined largely by the calcium, but as it is also affected by the phosphorus, one might expect that the constancy of the value as compared with that of calcium would be diminished unless the variations in the two substances were so related as to neutralize each other. As is well known, there is an apparent tendency in this direction and in these experiments it was found that on the whole the values for the sum showed less variation (coefficients 6.42 and 8.01 per cent) and were more uniformly distributed than those for calcium (Tables V and VI and Text-fig. 3). It is true that differences between groups were distinctly greater than in the case of calcium, but the agreement is sufficiently close to give evidence of a tendency to the maintenance of an inverse relation between serum calcium and inorganic phosphorus. Values for the product of calcium and inorganic phosphorus emphasize the phosphorus factor rather than the calcium, reversing the conditions that obtain in the case of the sum. A consideration of the product values given in Tables VII and VIII and Text-fig. 4 show that, while the order of variation is essentially the same as that of inorganic phosphorus (coefficients 17.09 and 17.29 per cent respectively), the distribution of values is more uniform. This may be attributable to the occurrence of coordinate variations in calcium and inorganic phosphorus. The situation presented by the values obtained for the ratio of calcium to inorganic phosphorus is somewhat surprising in that the ratio between the two substances proves to be less constant than the absolute amounts of either substance (Tables IX and X and Text-fig. 5). There are considerable differences between the standard values for individual groups of animals, and the distribution frequencies are inclined to be irregular. Moreover, all groups show a large standard deviation and correspondingly high coefficients of variation, but combining the results for the 4 groups of animals gives a fairly uniform and symmetrical distribution, a striking feature of which is the high frequency with which values occur over the entire range of standard variation, that is, from ratios of 2.85 to 4.29. It thus appears that, despite the evidence of a tendency to the observance of an inverse relation between the calcium and inorganic phosphorus in the blood, the ratio of one substance to the other is by no means constant. By using the product and the sum as a basis of expressing the relation between calcium and inorganic phosphorus, the form of the relation is ???
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PMID:CALCIUM AND INORGANIC PHOSPHORUS IN THE BLOOD OF RABBITS : I. RESULTS OF REPEATED AND PROLONGED OBSERVATIONS ON NORMAL RABBITS. 1986 30

The binding properties of a self-assembled coordination cage were subtly tuned by ancillary groups on the metal corners of the cage. Since the bulky mesityl groups of the ligand hang over the cage cavity, the effective cavity volume is reduced. Due to the tighter guest packing inside the shrunken cavity, smaller guests were efficiently bound and guest motion was restricted even at high temperatures.
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PMID:Noncovalent tailoring of the binding pocket of self-assembled cages by remote bulky ancillary groups. 2327 Mar 87

This study assessed the development of motor deficits in female hTau.P301S transgenic mice from 1.5 to 5.5 months of age. The test battery included clasping reflex, grid hanging, Rotarod test, spontaneous explorative activity, Catwalk gait analysis, and nest building. Starting from the age of 2-3 months the mice showed marked hyperactivity, abnormal placing of weight on the hindlimbs and defective nest building in their home cage. These behavioral impairments did not progress with age. In addition, there was a progressive development of hindlimb clasping, inability to stay on a rotating rod or hang on a metal grid, and gait impairment. Depending on the measured output parameter, the motor impairment became significant from 3 to 4 months onwards and rapidly worsened until the age of 5.5 months with little inter-individual variation. The progressive motor impairment was paralleled by a robust increase in AT8 p-tau positive neurons in deep cerebellar nuclei and pontine brainstem between 3 and 5.5 months of age. The quick and steadily progressive motor impairment between 3 and 5.5 months of age accompanied by robust development of tau pathology in the hindbrain makes this mouse well suited for preclinical studies aiming at slowing down tau pathology associated with primary or secondary tauopathies.
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PMID:Progressive age-dependent motor impairment in human tau P301S overexpressing mice. 3144 49

PlexinA1 (PlxnA1) is a transmembrane receptor for semaphorins, a large family of proteins that act as axonal guidance cues during nervous system development. However, there are limited studies on PlxnA1 function in neurobehavior. The present study examined if PlxnA1 deficiency leads to behavioral abnormalities in BALB/cAJ mice. PlxnA1 knockout (KO) mice were generated by homologous recombination and compared to wild type (WT) littermates on a comprehensive battery of behavioral tests, including open field assessment of spontaneous ambulation, state anxiety, and grooming, home cage grooming, the wire hang test of muscle strength, motor coordination on the rotarod task, working memory on the Y maze alternation task, cued and contextual fear conditioning, anxiety on the elevated plus maze, sociability to intruders, and sensory processing as measured by prepulse inhibition (PPI). Measures of motor performance, working memory, fear memory, and sociability did not differ significantly between genotypes, while PlxnA1 KO mice displayed excessive self-grooming, impaired PPI, and slightly lower anxiety. These results suggest a crucial role for PlxnA1 in the development and function of brain regions controlling self-grooming and sensory gating. PlxnA1 KO mice may be a valuable model to investigate the repetitive behaviors and information processing deficits characteristic of many neurodevelopmental and psychiatric disorders.
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PMID:PlexinA1 deficiency in BALB/cAJ mice leads to excessive self-grooming and reduced prepulse inhibition. 3316 87