The tail suspension test (TST) and forced swimming test (FST) are widely used for assessing antidepressant activity and depression-like behavior. We found that CS mice show negligible immobility in inescapable situations. Quantitative trait locus (QTL) mapping using CS and C57BL/6J mice revealed significant QTLs on chromosomes 4 (FST) and 5 (TST and FST). To identify the quantitative trait gene on chromosome 5, we narrowed the QTL interval to 0.5 Mb using several congenic and subcongenic strains. Ubiquitin-specific peptidase 46 (Usp46) with a lysine codon deletion was located in this region. This deletion affected nest building, muscimol-induced righting reflex and anti-immobility effects of imipramine. The muscimol-induced current in the hippocampal CA1 pyramidal neurons and hippocampal expression of the 67-kDa isoform of glutamic acid decarboxylase were significantly decreased in the Usp46 mutant mice compared to control mice. These phenotypes were rescued in transgenic mice with bacterial artificial chromosomes containing wild-type Usp46. Thus, Usp46 affects the immobility in the TST and FST, and it is implicated in the regulation of GABA action.
The tail suspension test (TST) is widely recognized as a useful experimental paradigm for assessing antidepressant activity and depression-like behavior. We have previously identified ubiquitin-specific peptidase 46 (Usp46) as a quantitative trait gene responsible for decreasing immobility time in the TST in mice. This Usp46 mutation has a 3-bp deletion coding for lysine in the open reading frame, and we indicated that Usp46 is implicated in the regulation of the GABAergic system. However, it is not known precisely how the immobile behavior is regulated by the GABAergic system. Therefore, in the present study, we examined whether the immobility time is influenced by drugs affecting the action mediated by GABAA receptor using both 3-bp deleted (the Usp46 mutant) and null Usp46 (Usp46 KO) mice. Nitrazepam, an agonist at the benzodiazepine-binding site of the GABAA receptor, which potentiates the action of GABA, produced a dose-dependent increase in TST immobility time in the Usp46 mutant mice without affecting general behaviors. The Usp46 KO mice exhibited short immobility times comparable to the Usp46 mutant mice, which was also increased by nitrazepam administration. The effects of nitrazepam in the Usp46 mutant and KO mice were antagonized by flumazenil. These results indicate that the 3-bp deleted Usp46 mutation causes a loss-of-function phenotype, and that the GABAA receptor might participate in the regulation of TST immobility time.
The dynamic palatograph is an electrical apparatus that generates a visual display of constantly changing palatolingual contact as a function of time, using an artificial palatal plate with affixed electrodes. This paper describes a technique of speech therapy incorporating dynamic palatography for a cleft palate patient. The patient, a 6-year-old Japanese girl with a repaired unilateral cleft lip and palate, had been judged to demonstrate articulation disorders involving contact of the tongue with the hard palate or alveolus following surgical improvement of velopharyngeal function. Prior to therapy the tongue tended to contact the hard palate more posteriorly than normal. After therapy with the dynamic palatograph, palatolingual contact was normal in comparison with average speakers. Our findings suggest that the facility of constant visual indication of tongue posture to the clinician and patient during corrective speech therapy using dynamic palatography may expedite results with cleft palate patients in the speech clinic when implemented in a carefully structured treatment plan.
Rehabilitation of the oral cancer patient should aim to achieve not only morphological restoration but also post-operative functions. However, there are few reports describing quantitative evaluation of the latter. The authors have attempted quantitative evaluation of post-operative articulatory function after glossectomy, and report the evaluation of it by speech intelligibility, electropalatography (EPG), and acoustical analysis. Subjects were five directly sutured patients and five patients reconstructed with forearm flap, all after glossectomy. The target syllable was /ta/ from among speech intelligibility test samples. The speech intelligibility and acoustical analysis were investigated pre-operation, and 1,6 and 12 months post-operation. EPG data were collected by DP-01(RION) at 6 months post-operation. Acoustical analyses were carried out by consonant frequency characteristics and formant variance from consonant to vowel transitions. As a result, subjects reconstructed with a forearm flap showed higher restorative tendency than directly sutured subjects. Articulatory characteristics expected from acoustical analysis were more in agreement with the results of EPG than with the results of the speech intelligibility test. From the results, it was suggested that the acoustical analysis used for this research could reveal changes in articulatory movement and will be useful for quantitatively evaluating post-operative articulatory functions.
We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST) and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92), and mice with this mutation (MT mice), as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA) receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT) or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system.
Lingual-palatal contact patterns and auditorily judged misarticulations, classed as palatalized misarticulation (PM), lateral misarticulation (LM), nasopharyngeal misarticulation (NM), and other distortions were compared in 53 Japanese cleft palate patients. Velopharyngeal function of these patients was considered within normal limits. Contact patterns were recorded by electropalatography (EPG) in an attempt to objectively categorize the misarticulations of cleft palate speakers including those previously reported in English. It is concluded that these lingual-palatal contact patterns are characterized by a broader and/or more posterior pattern than found in normal speakers, although considerable variability was noted.
ABSTRACT. Segmental hypoplasia not associated with vertebral abnormalities was found in a Japanese Black calf that was unable to stand. Constriction occurred between the third and 5th segments of the lumbar spinal cord, and was most severe in the 4th segment. Myelodysplasia, such as hydromyelia and syringomyelia, absence or interruption of the central canal, dysplasia of the gray matter, and absence or divergence of the septal connective tissue at the dorsal median septum or the ventral median fissure, were confirmed histologically. These changes indicate hypoplasia of the segments affected following neural tube closure. Therefore, this case was suspected to be a closed neural tube defect. KEY WORDS: Japanese Black calf, myelodysplasia, segmental hypoplasia of the spinal cord.J. Vet. Med. Sci. 71(3): 337-340, 2009 Congenital abnormalities of the spinal cord have been described collectively as myelodysplasia or dysraphic states [7,10]. In cattle, the occurrence of spina bifida, a spinal neural tube closure defect, is common [8]. Hypoplasia of the spinal cord is defined as a reduced development of one or more segments of the spinal cord [10]. In cattle, this hypoplasia has been reported in Angus and other breeds [7,8]. Although these reports described only the brief clinical signs of the affected animal [8], abnormalities in appearance, pathological changes and other details of the animals were not reported. Constriction or absence of the spinal cord have always been associated with vertebral abnormalities such as segmental aplasia of the spinal cord [4,9], perosomus elumbis [6] and spinal stenosis [3].In this study, we describe a rare anomaly of the spinal cord, namely, segmental hypoplasia of the spinal cord in a calf that was not associated with vertebral abnormalities. The morphological changes of the malformed spinal cord were examined, and their pathogenesis was discussed from an embryological viewpoint. The subject was a male Japanese Black calf that was unable to stand after birth. His left forelimb and right hindlimb were not flexible and exhibited only mild convulsion. In general appearance, spinal defects could not be confirmed. Although the calf was born 2 weeks before the expected delivery date, the general conditions, such as vigor and appetite, were fine. The calf was euthanized after one month according to the request of the owner of the animal, and a postmortem examination was performed. The weight of the calf before the necropsy was 42 kg, indicating a reduced growth compared to normal calves. It was the first delivery of the cow, which went through a normal pregnancy and did not receive the administration of any drugs. No similar cases have been reported from the maternal or paternal line of the calf.The necropsy confirmed a constriction between the third (L3) and fifth (L5) segments of the lumbar spinal cord, with the constriction in the fourth segment (L4) being the most severe (diameter: approx. 6 mm) (Fig. 1). Despite a mild dorsal curvature of the spine, no spinal canal narrowing or abno...
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