c-Fos expression in the auditory pathways related to the significance of acoustic signals in rats performing a sensory-motor task

Neuronal activity was established in the auditory pathways in relation to behavioural response and cognitive information processing during a sensory-motor acoustic learning. Rats were trained in three consecutive phases. The first phase was an association between an auditory stimulus and a food reward; the second phase a simple discrimination between two sounds of different frequency components, and the third phase a more complex discrimination involving both spectral and spatial sound dimensions. Auditory stimuli were bursts of complex sounds lasting 500 ms. Neuronal activity related to the behaviourally relevant stimuli was established in 20 "learning" rats undergoing this protocol, which were progressively sacrificed at the beginning, middle and end of each phase. For comparison, activity was also established in four "control" rats exposed to the same stimuli delivered pseudo-randomly, thus carrying no behavioural meaning. Neuronal activity was assessed immunocytochemically using the functional marker Fos. To establish a baseline, two rats were unexposed to controlled acoustic stimulation ("unstimulated" rats). In the superior olivary complex (SOC), inferior colliculus (IC) and medial geniculate body (MGB), the number of Fos-like immunopositive cells was comparable in "learning" and "control" animals, but higher than in the "unstimulated" rats. In the auditory cortex (AC), most prominently in the secondary area Te2, the number of Fos-like positive cells differed between "learning" and "control" rats, suggesting that the auditory cortical areas may be involved in the encoding of the behavioural significance of the acoustic stimuli.     

Excitability of spinal cord and gracile nucleus neurons in rats with chronically injured sciatic nerve examined by c-fos expression

Low-threshold sensory pathways have been suggested to have an important role in the formation and maintenance of sensory abnormalities which are observed after peripheral nerve injury. Fos-like immunoreactive (Fos-LI) neurons are expressed in spinal cord laminae III-IV and the gracile nucleus by electrically stimulating the injured nerves at Abeta strength after sciatic nerve transection in rats. This suggests that the excitability of these neurons is increased by nerve injury. In this study, we investigated which receptors are involved in the regulation of the increased excitability in spinal and gracile nucleus neurons. The sciatic nerve of Sprague-Dawley rats (150 g) was transected 7 days before the experiment day. The rats were administered morphine, muscimol, baclofen, MK-801, CNQX, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) or clonidine i.p., and then electrically stimulated at 0.1 mA to the proximal region to the nerve injury site under urethane anesthesia. Two hours after the stimulation, Fos-LI expression was increased in the spinal cord dorsal horn and the gracile nucleus in control rats. Baclofen inhibited the Fos-LI expression both in the spinal cord and the gracile nucleus. Morphine inhibited only the Fos-LI expression in the posterior cutaneous (PC) nerve territory of laminae I-II, but not in the sciatic nerve (SC) territory, laminae III-IV nor the gracile nucleus. MK-801 had an inhibitory but complicated effect in laminae I-II and the gracile nucleus. The other drugs were not effective on Fos-LI expression. It is suggested that the GABA(B) receptor has a pivotal role in the regulation of Fos-LI expression after electrical stimulation to the injured low-threshold sensory fibers, and other receptors have little effect on the Fos-LI expression.     

Platelet-activating factor receptor is not required for long-term potentiation in the hippocampal CA1 region

From pharmacological studies, platelet-activating factor (PAF) has been proposed as a retrograde messenger for long-term potentiation (LTP) in the hippocampal CA1 region. We re-examined a possible contribution of PAF to LTP with a more specific approach using mice deficient in the PAF receptor. The PAF receptor-deficient mice exhibited normal LTP and showed no obvious abnormality in excitatory synaptic transmission. We also performed pharmacological experiments on the wild-type mice. Two structurally different antagonists of PAF receptors had no effects on LTP. Furthermore, the application of PAF itself caused no detectable changes in excitatory synaptic transmission. Thus, we conclude that the PAF receptor is not required for LTP in the CA1 region. Introduction     

Association Study of Parathyroid Hormone Gene Polymorphism and Bone Mineral Density in Japanese Postmenopausal Women

Association of BST B1 restriction fragment length polymorphism (RFLP) of the parathyroid hormone (PTH) gene with bone mineral density (BMD) was examined in 383 healthy postmenopausal women in Japan who were unrelated. The RFLP was represented as B or b, the capital letter signifying the presence of and the small letter the absence of restriction site for BST B1. The frequency of each genotype—BB, Bb, and bb—was 82.5%, 16.7%, and 0.8%, respectively. When we statistically compared age, years after menopause, body height, and body weight between the BB genotype and the Bb genotype groups, there was no significant difference between the groups. However, the lumbar BMD and the score of BMD adjusted for age and body weight (Z score) were significantly lower in the group of genotype Bb than in the BB: 0.859 ± 0.019 g/cm² versus 0.925 ± 0.011 (mean ± SE, P= 0.01) and −0.412 ± 0.138 versus 0.067 ± 0.082 (mean ± SE, P= 0.01). In addition, the Z score of total body BMD in the Bb genotype group was lower than that in the BB group. Comparison of serum and urinary biochemical bone metabolic markers suggested that the subjects with Bb genotype might be in a relatively higher state of bone turnover than those with BB genotype. These results suggest that the polymorphism in the PTH gene would be a useful genetic marker for lower BMD and the susceptibility for osteoporosis. Received: 19 March 1998 / Accepted: 24 June 1998     

Screening for mutations in candidate genes for hypospadias

Hypospadias, a condition with a frontally placed urethral orifice on the penis, is the most common malformation in males. During fetal development several components are necessary for normal male genital development. Testosterone and dihydrotestosterone act via the androgen receptor but a defective receptor function results in different degrees of genital malformations. Testosterone-5α-reductase converts testosterone to dihydrotestosterone, which is crucial for normal differentiation, and a total lack of this enzyme results, in syndromes with hypospadias. The Wilms' tumour 1 (WT1) gene is expressed in the fetal gonad and genital malformations can occur due to WT1 gene mutations. These genes are therefore strong candidate genes for hypospadias. We have analysed 35 boys with hypopadias and one girl diagnosed as with complete androgen insensitivity syndrome, using exon by exon polymerace chain reaction (PCR) amplification of the AR, WT1 and 5α-reductase genes and screened for point mutations and performed subsequent DNA sequencing. No mutations in any of these genes were found in the 26 patients with isolated hypospadias. Two patients with severe hypospadias with cryptorchidism were found to carry mutations in the androgen receptor gene. Also the girl with clinically diagnosed complete androgen insensitivity was found to be homozygous for a splice mutation in the 5α-reductase gene. In summary, mutations in the WT1, AR and 5α-reductase genes are not common causes of isolated hypospadias. Received: 1 October 1997 / Accepted: 4 May 1998     

c-fos基因在乐果中毒后肌无力大鼠肌组织中的表达

采用ＲＴ－ＰＣＲ、ＷｅｓｔｅｒｎＢｌｏｔ技术,检测了有机磷农药乐果对大鼠骨骼肌细胞中即刻早期反应基因ｃ－ｆｏｓ表达的影响。结果表明,在乐果作用下,骨骼肌细胞ｃ－ｆｏｓ基因表达在ｍＲＮＡ以及蛋白质水平均明显增高。然而骨骼肌细胞ｃ－ｆｏｓ的表达是否与毒物刺激有关,其在农药中毒机制上的生物学意义有待深入研究。     

免疫状态对Fv—4基因抗Friend MuLV作用的影响

通过检测免疫抑制的Ｆ１小鼠和杂合子Ｆ２裸鼠对Ｆｒｉｅｎｄ小鼠白血病病毒（Ｆｒ．ＭｕＬＶ）感染的敏感性,探讨免疫状态对Ｆｖ－４基因（特别是对Ｆｖ－４基因杂合子）抗ＦｒｉｅｎｄＭｕＬＶ作用的影响,经腹腔接种Ｆｒ．ＭｕＬＶ病毒液攻击小鼠或Ｆ２裸鼠后,检查其计中Ｆｒ．ＭｕＬＶ的增主其发病情况,结果表明,免疫抑制的Ｆ１小鼠和杂合子Ｆ１裸鼠都可被Ｆｒ．ＭｕＬＶ脾脏中有病毒增殖,并用约２／３的杂合子Ｆ２裸鼠与Ｂ     

氯化甲基汞对大鼠脑神经细胞凋亡及P^53基因表达的影响

选用Ｗｉｓｔａｒ系雄性大鼠,经皮下注射给予１０ｍｇ／Ｋｇ体重氯化甲基汞（ＣＨ３ＨｇＣｌ）,连续７天,第１５天取其脑组织,利用细胞和分子生物学技术进行ＤＮＡ电泳和流式细胞术（ＦＣＭ）分析。实验结果,染毒组大鼠脑组织ＤＮＡ电泳呈现特征性梯形电泳带;ＦＣＭ分析染毒组大鼠脑神经细胞的凋亡率、Ｐ５３基因表达率显著高于对照组（Ｐ＜０．０５）。结果表明：ＣＨ３ＨｇＣｌ以诱导凋亡方式导致脑神经细胞损伤,Ｐ５３基因参与ＣＨ３ＨｇＣｌ诱导脑神经细胞凋亡的基因调控过程。