Strain differences in the sleep of rats

Sleep was measured in two inbred rat strains (Lewis and Brown Norway) and their F1 hybrids to investigate patterns of inheritance and to provide a starting point for future studies of F2 and recombinant rats. Recordings from chronically implanted electrodes were quantified and scored by a computerized system; results were evaluated by an analysis of variance with pairwise comparisons by the Tukey HSD test. Brown Norway rats had the highest paradoxical sleep (PS) percentages; Lewis rats had the lowest. Hybrid rats had PS percentages intermediate between parent strains and significantly different from both. These results suggest codominance or multigenic transmission of PS amounts. There were no group differences of number of PS bouts; Brown Norway and hybrid rats had longer bouts than Lewis rats. Lewis and hybrid rats had similar amplitudes of the diurnal rhythm of PS, which were higher than those of Brown Norway rats; single gene transmission remains possible for diurnal rhythm amplitude. Thus, inheritance of PS percentage and rhythm amplitude appear independent. No group differences in PS latency were found.     

Strain differences of the light-dark preference in inbred rats

he present study examined strain differences in the light-dark preference among four strains of rats. The test was done in the home-cage situation under 12L:12D cycles. Data from four strains were compared: BN/Kyo, BDIX/Nem, Wistar/Nu, and F344/NSlc. These strains differed in the light-dark preference measured by the ratio of the time spent in the field area of the home cage during the light period. BN/Kyo and BDIX/Nem spent the most time (approx. 23%) in the field during the light period, while F344/NSlc spent the least time (approx. 5%). Wistar/Nu fell between the two (approx. 12%).This study was conducted as partial fulfillment for the master's degree, submitted to Nagoya University by the first author. It was presented at the 47th Annual Conference of the Japanese Society of Animal Psychology.     

Strain differences in Fos expression following airpuff startle in Spontaneously Hypertensive and Wistar Kyoto rats

The airpuff startle stimulus elicits both a behavioral and a concurrent sympathetic and parasympathetic activation, which have been shown to differ between inbred normotensive Wistar Kyoto and Spontaneously Hypertensive rat strains. Neither the brain sites responsible for the cardiovascular and motor responses, nor the origins of the strain differential responses, have yet been elucidated. The goals of the present study were (i) to define the neuronal pattern of immunoreactive Fos expression to the airpuff stimulus, and (ii) to determine whether this pattern of expression differed between the two contrasting inbred rat strains, thereby relating to observed differences in response. The airpuff stimulus induced Fos protein expression in discrete nuclei within the hypothalamus, thalamus, midbrain, pons and medulla of both strains, with strain-dependent differences evident in the hypothalamus (lateral, ventromedial and dorsomedial), pons (locus coeruleus) and medulla (rostroventrolateral medulla and solitary tract nuclei). To remove Fos expression arising from test chamber novelty, which was observed in both strains, a subset of animals was habituated to the test chamber for four days prior to testing. Habituation reduced Fos expression in several brain regions in the Wistar Kyoto, but failed to do so in the Spontaneously Hypertensive rat. The present results are the first to identify a set of brain regions likely to be responsible for the mediation of the cardiovascular and motor responses associated with the airpuff startle stimulus. Several of the identified areas contain neurotransmitters implicated by prior pharmacological studies. Further, these data identify differences in the degree of activation of specific neuronal structures that probably underlie strain differences in the cardiovascular response to the airpuff. Additionally, the results provide a cellular correlate to reported deficits in behavioral habituation by the Spontaneously Hypertensive rat and suggest a potentially profound difference between the ability of these two strains to adapt to repeated mild stress stimuli.     

Strain differences in the expression of the Epa-1-restricting element

Epa-1-specific cytotoxic T lymphocytes (CTL) lyse epidermal cells (EC) of different Epa-1+ H-2k strains, such a AKR, CBA, C58, and RF, at different levels. We used an H-2Kk-specific monoclonal antibody (mAb) to test the hypothesis that this phenomenon is due to differences in the H-2-restricting element. Initially, we established the specificity of this mAb for the Epa-1-restricting element by demonstrating its capacity to inhibit the lysis of CBA EC by Epa-1-specific CTL. We then used it as the probe in a cellular radioimmunoassay to quantify the expression of the restricting element by EC of different H-2k strains. We found that C58 and RF EC bound significantly less of the mAb than did CBA EC. Although AKR also bound less of the mAb than did CBA EC, the difference was not statistically significant. To examine the generality of this phenomenon, we quantified the expression of Kk antigens on spleen cells (SC) of the same four strains. We found that RF SC, but not AKR or C58 SC, bound significantly less of the Kk mAb than did CBA SC. Thus, the differential CTL lysis of Epa-1+ EC of different strains probably reflects differences in expression of the H-2-restricting element rather than of the nominal antigen.     

Stereological investigation and expression of calcium-binding proteins in developing human inferior colliculus

The mammalian inferior colliculus (IC) is a major relay nucleus in the auditory pathway. Prenatal development of the human IC has been inadequately studied. The present study reports the morphometric development and maturation of the human IC using unbiased stereology, in 18 aborted fetuses of various gestational ages (12–29 weeks) and two babies aged 40 postnatal days (PND) and 5 months (that died of postoperative complications). It also demonstrates the functional maturation of the IC by examining the expression of calcium-binding proteins – parvalbumin (PV) and calbindin (CB). There was a significant increase in the total number of neurons and glia from 18 weeks of gestation (WG). The glia and neuron volume increased significantly from 16 WG to 22 WG, respectively. The total volume of IC also increased significantly from 18 WG onwards. On the other hand, the number and volume of undifferentiated cell bodies across all ages decreased significantly. Expression of CB was concentrated in the dorsal cortex while that of PV was mainly confined to the central nucleus of the IC, possibly indicating an early segregation of parallel processing of information in the auditory pathways. Intense staining for CB in the soma and dendrites appeared earlier than that of the PV. The morphological maturation appeared to overlap the onset of functional maturation suggesting an activity-dependent mechanism in the development of IC.     

Strain differences of the ability to hydroxylate methotrexate in rats.

Converting activity of methotrexate (MTX) to 7-hydroxymethotrexate (7-OH-MTX) was examined using eight strains of rats. Marked variability of the activity was found in liver cytosols from the rats. The highest activity was observed with Sea:SD rats, followed by LEW/Sea and Jcl:Wistar rats. The lowest activity was observed with WKA/Sea rats. The difference in the activity between Sea:SD and WKA/Sea strains was 104-fold. The variation was correlated to the strain difference of benzaldehyde oxidase activity in the rats. The cytosolic 7-hydroxylase activities in other tissues of Sea:SD rats were much higher than those of WKA/Sea, similarly to the case in liver. The liver microsomes of Sea:SD rats exhibited no 7-hydroxylase activity toward MTX even in the presence of NADPH. The cytosolic 7-hydroxylating activity of the livers of Sea:SD rats was inhibited by menadione, beta-estradiol, chlorpromazine and disulfiram, inhibitors of aldehyde oxidase, but not oxypurinol, an inhibitor of xanthine oxidase. The purified aldehyde oxidase from the livers of Sea:SD rats exhibited a significant 7-hydroxylating activity toward MTX. However, xanthine oxidase had no ability to hydroxylate MTX. These facts suggest that MTX hydroxylating activity in rats is predominantly due to aldehyde oxidase, and the strain differences are due to the variations of the flavoenzyme level.     

Expression of calcium-binding proteins in the mouse claustrum

The present paper describes the distribution of three calcium-binding proteins (calbindin D28k, calretinin, and parvalbumin) in the mouse dorsal claustrum and endopiriform nucleus. The three calcium-binding proteins were distinctly expressed in structures of both the claustrum and the endopiriform nucleus. Calbindin was the calcium-binding protein showing the highest expression in the claustrum and the endopiriform nucleus. In contrast, calretinin-immunoreactive structures, particularly cell bodies, were very scarce in these regions. Both calbindin-immunoreactive and parvalbumin-immunoreactive neurons were more abundant in the claustrum than in the endopiriform nucleus, and more in rostral than in caudal levels. Nevertheless, calcium-binding protein immunoreactive neurons constitute a minority population of claustral neurons. The colocalization study of calbindin and parvalbumin immunoreactivities has demonstrated that both calcium-binding proteins are mostly expressed by separate claustral neurons in the mouse. On the other hand, our results on parvalbumin and calretinin immunoreactivity match a novel subdivision of the mouse claustrum mostly based on the pattern of cadherin expression [Neuroscience 106 (2001) 505]. In this sense, we propose that a specific zone of the dorsal claustrum with cell bodies that strongly express Rcad and cadherin-8 would be the selective target for parvalbumin-expressing fibers, and that they would be mostly avoided by calretinin-expressing axons.     

Differential expression of calcium-binding proteins in the red nucleus of the developing and adult human brain

The adult human red nucleus consists of two parts: (1) the parvocellular part, which is clearly separated from (2) the magnocellular part. The latter and its rubrospinal projection is known to be rudimentary in the adult human brain. Information concerning the fetal or neonatal features of the red nucleus is sparse. This study is aimed at providing a detailed account of the distribution of three calcium-binding proteins: calretinin (CR), calbindin (CB), and parvalbumin (PV), which are known to be expressed in distinct neuronal populations. Special attention has been paid to transient phenomena. CB was the most abundant protein in the magnocellular part in fetal and perinatal brains; immunoreactive (ir) neurons appeared numerous and densely packed. In the adult only few and widely spaced ir nerve cells were present. CR-expression largely corresponds to that of CB, except that fewer neurons were immunolabelled. In double- labellings the majority of neurons expressed both CB and CR; a moderate number of nerve cells solely expressing CR was present in the magnocellular part. PV-ir fibers and a moderate number of small cells were observed in the fetal, perinatal as well as the adult parvocellular part. A few PV-ir neurons were seen in the magnocellular part of the fetal and perinatal brains. Our results indicated that: (1) the magnocellular and parvocellular parts of the red nucleus were well-demarcated portions from fetal life onwards, thus a dominance of the parvocellular part over the magnocellular occurred during development; (2) the magnocellular part was more prominent in the fetal period than in adulthood; (3) neurons in the red nucleus were heterogeneous with respect to the immunoreactivities towards the three calcium-binding proteins examined; (4) the transient prominence of the magnocellular part might be a substrate for a specific transitory pattern of motor behaviour. Accepted: 7 September 2000     

Strain differences in hippocampal EEG are related to strain differences in behaviour in rats

To date, EEG studies towards strain differences have focussed on pharmacologically altered or pathological EEG activity, but only few studies have investigated strain differences and normal EEG activity. A strong relation between behaviour and EEG activity has been demonstrated, especially for hippocampal EEG activity. This relation is known to be similar across species and strains, but no direct comparisons between rat strains within one study have been made. This study compared two rat strains (Sprague-Dawley and Long-Evans) with regard to open-field behaviour and concurrent hippocampal EEG recordings. A detailed behavioural analysis was made and spectral power was calculated for corresponding EEG activity in eight frequency bands. The two strains differed in exploratory activity and in spectral power in the 9-10-Hz frequency band (high frequency rhythmical slow activity [RSA] 6-10 Hz). Long-Evans rats showed higher exploratory activity and higher 9-10 Hz spectral power for voluntary movement and sniffing behaviours. Our results demonstrated these behaviour-specific strain differences in RSA power, although the relation between EEG and behaviour within each strain was similar. The strain differences in EEG were interpreted in relation to strain differences in exploratory behaviour, attributing the differences to a main motor component but also to a smaller sensory component integrated in exploratory behaviour. This is in accordance with theories on the sensory-motor function of the hippocampus and hippocampal theta activity.     

Strain differences in baroceptor reflex in adult wistar kyoto rats

OBJECTIVES

A subset of normotensive Sprague–Dawley rats show lower baroreflex sensitivity; however, no previous study investigated whether there are differences in baroreflex sensitivity within this subset. Our study compared baroreflex sensitivity among conscious rats of this specific subtype.

METHODS

Male Wistar Kyoto (WKY) rats (16 weeks old) were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure (MAP) and heart rate (HR). Baroreflex gain was calculated as the ratio between change in HR and MAP variation (ΔHR/ΔMAP) in response to a depressor dose of sodium nitroprusside (SNP, 50 μg/kg, i.v.) and a pressor dose of phenylephrine (PE, 8 μg/kg, i.v.). Rats were divided into four groups: 1) low bradycardic baroreflex (LB), baroreflex gain (BG) between -1 and -2 bpm/mmHg tested with PE; 2) high bradycardic baroreflex (HB), BG < -2 bpm/mmHg tested with PE; 3) low tachycardic baroreflex (LT), BG between -1 and -2 bpm/mmHg tested with SNP and; 4) high tachycardic baroreflex (HT), BG < -2 bpm/mmHg tested with SNP. Significant differences were considered for p < 0.05.

RESULTS

Approximately 37% of the rats showed a reduced bradycardic peak, bradycardic reflex and decreased bradycardic gain of baroreflex while roughly 23% had a decreased basal HR, tachycardic peak, tachycardic reflex and reduced sympathetic baroreflex gain. No significant alterations were noted with regard to basal MAP.

CONCLUSION

There is variability regarding baroreflex sensitivity among WKY rats from the same laboratory.     

Ethnic differences in expression of the dysregulated proteins in uterine leiomyomata

BACKGROUND: Black ethnicity is one of the risk factors for uterine leiomyomata (ULM). Little is known about the ethnic differences in leiomyoma-associated gene products in women with uterine leiomyomata. METHODS: A total of 120 hysterectomies with ULM were collected from black, Asian, Hispanic and white women (30 cases from each group). Twenty-two gene products were selected for the study. The expressions of the selected dysregulated gene products were measured by the semiquantification and the immunoscores were normalized by matched myometrium. RESULTS: The relative expressions of progesterone receptor A (PR-A) (up-regulation), retinoid acid receptor alpha (down-regulation), and retinoid X receptor alpha (RXRalpha) (no change) in leiomyomata compared to normal myometrium in black women were significantly different compared to other ethnic groups (P < 0.05). About one-third of ULM from black women subclustered together in association with a group of up-regulated gene products. Many other gene products, including local growth factors, insulin-like growth factor (IGF)-signalling proteins, and cell proliferation markers, were dysregulated in ULM but showed non-significant differences between the ethnic groups. CONCLUSIONS: There are substantial differences of the sex steroid receptors and other nuclear receptors between black women and other ethnic groups. Based on tissue microarray data, there are at least two broad groups of leiomyomata presented by the dysregulation of different groups of gene products. One is dominated by up-regulation of amplified in breast cancer 1, CD24, hamartin, human mobility group gene 2, IGF2, PR-A and RXR, and the other is characterized by up-regulation of epithelial growth factor receptor, down-regulation of hamartin, PR-A and tuberin.     

Immunoreactivity for calcium-binding proteins in the claustrum of the monkey

 The claustrum is topographically and reciprocally connected with many different cortical areas, and anatomical and physiological data suggest it is composed of functionally distinct subdivisions. We asked if the distribution of cells immunoreactive for three calcium-binding proteins, parvalbumin, calbindin D-28k and calretinin would delineate functional subdivisions in the claustrum. We also asked if, as in cortex, different cell types were immunoreactive for the different proteins. We found that cells with parvalbumin-ir were large, multipolar cells. Cells immunoreactive for calretinin were bipolar cells with elongated cell bodies and beaded dendrites. There were three different types of cells immunoreactive for calbindin. The most numerous were small cells with round or oval cell bodies and numerous fine, winding processes. A second type were large multipolar, cells that resembled the parvalbumin-ir cells. The third class were bipolar cells with large, elongated cell bodies. Each type of cell resembles a cell type described in earlier Golgi studies, and each has a morphological cortical counterpart. While the different cell types varied in density, each was seen over the anterior-posterior and dorsal-ventral extent of the claustrum. Accepted: 21 July 1998     

Strain differences in rats with respect to speed of conflict resolution

Speed of conflict resolution was studied in a conditioned punishment paradigm in a Skinner box and a straight runway. In both experimental situations speed of conflict resolution was defined as the latency to gain food during an approach-avoidance conflict. In the Skinner box Tryon Maze Bright rats were faster in speed of conflict resolution than Tryon Maze Dull rats, and Roman Low Avoidance rats were faster than Roman High Avoidance rats. In the runway situation, Wistar Kyoto rats were faster in solving the conflict than randomly bred Wistar Wu rats and Brown Norway rats were faster than Wistar Wu rats. Differences between the strains in speed of conflict resolution could not be consistently explained from strain differences in approach or avoidance behavior, measured separately. It is, therefore, suggested that speed of conflict resolution is a unique parameter.This investigation was supported by grants from the Netherlands Psychonomics Foundation (NWO No. 15-26-12 and NWO No. 15-25-28).     

Motor cortical excitability and clinical response to rTMS in depression

BACKGROUND: The relationship between frontal lobe activity in the left and right hemispheres and the pathophysiology of depression remains unclear. In addition, it is uncertain whether levels of frontal or motor cortical excitability relate to clinical response to treatment modalities. We aimed to explore whether motor cortical excitability as assessed with single and paired pulse transcranial magnetic stimulation (TMS) could be used to predict the response to treatment with repetitive TMS (rTMS) applied to the left or right prefrontal cortex. METHODS: Motor thresholds, cortical excitability and cortical inhibition (CI) were assessed prior to a trial of rTMS in patients with treatment resistant depression. RESULTS: There was no consistent pattern of differences in hemispheric activity, although there was a relationship between the degree of psychopathology and cortical excitability (right hemisphere) and an inverse relationship between inhibitory activity and clinical response (left hemisphere). CONCLUSIONS: The study does not support a simple model of laterality in motor cortical excitability in depression. The TMS measures used in this study appear to be of limited use in the prediction of clinical response to rTMS.     

电针上调MCAO大鼠皮质缺血半暗带脑红蛋白的表达

目的:探讨电针对MCAO大鼠大脑皮质缺血神经元的保护机制.方法:通过线栓法梗塞大脑中动脉建立大鼠局灶性缺血模型,在缺血1h后给予电针0.5 h(取穴为足三里、曲池),以后1次/d.在电针1d、3 d和7d分别处死,用Nissl染色观察神经元损伤,用免疫组织化学和Western blot测定缺血半暗带脑红蛋白表达的变化.结果:电针组与非电针组和正常组比较在1d和3d两个时间段缺血半暗带脑红蛋白表达均有增高(P＜0.01),7d时差异均无显著性(P＞0.05);非电针组与正常组比较缺血半暗带脑红蛋白表达,1d、3d两个时间有显著性增高(P＜0.01),7d时差异也无显著性(P＞0.05).结论:缺血能增加急性期缺血半暗带脑红蛋白的表达,而电针对该蛋白表达的提高更有显著性,可能对缺血缺氧的神经元具有较好的保护作用.     

Sexual differences in the neonatal serotonin effect on hormone secretion in rats

A number of authors in the literature have reported facilitatory or inhibitory effects of serotonin (5-HT) on gonadotropin secretion, sexual hormones content or sexual behavior, but little information has been reported about the possible role of serotonin administered during the critical period of sexual differentiation. To test this possibility, we have injected a 5-HT intraventricularly to neonate male and female rats in order to examine the influence during the critical period of this single treatment on the adult sexual hormone content and sexual behavior. Neonatal administration of 5-HT in the brain decreases significantly estradiol content of adult females, without affecting testosterone level in males. Neither male nor female sexual behavior was affected by 5-HT injection on day 1 of life. These data evidence a sexual difference of serotonin administration during the critical period on gonadal hormones secretion in adulthood.     

皮层电刺激对左旋多巴诱发异动症大鼠纹状体c-fos及ENK表达的影响

为了研究皮层电刺激对左旋多巴诱发异动症(LID)大鼠纹状体神经元c-fos及脑啡肽(ENK)表达的影响,探讨皮层-纹状体通路可塑性改变在LID发生机制中的作用,本实验制备Parkinson病(PD)和LID大鼠模型,将实验大鼠分成三组:正常对照组、PD组和LID组。电刺激运动皮层后,免疫组化法检测纹状体区c-fos、ENK、细胞外信号调节激酶1/2(ERK1/2)及其活化形式磷酸化细胞外信号调节激酶1/2(p-ERK1/2)的表达。结果显示:与对侧比较,皮层电刺激使各组同侧纹状体c-fos、ENK、ERK1/2、p-ERK1/2表达均增加(P<0.01);LID组c-fos(0.67±0.03)以及p-ERK1/2的表达(0.17±0.05)较PD组(0.08±0.03)和正常组(0.07±0.02)增加(P<0.05),LID组ENK(0.21±0.07)的表达和PD组(0.18±0.08)相比较无统计学差异(P>0.05),但均较正常组(0.08±0.01)增加(P<0.01);三组ERK1/2的表达无统计学差异(P>0.05),但LID组p-ERK1/2的表达(0.17±0.05)较PD组和正常组有所增加(P<0.01)。本研究结果表明,LID大鼠皮层-纹状体通路兴奋使纹状体c-fos以及p-ERK1/2表达增加,ENK的表达没有显著变化。上述结果提示皮层-纹状体通路活动增强以及p-ERK1/2表达的增加与LID的发生机制有关,而ENK在LID的发生过程中可能不发挥重要作用。     

The influence of low-frequency rTMS on EEG of rats

This study aimed to determine the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on electroencephalograms (EEGs) of rats. Fifteen Sprague-Dawley rats were subject to 100 pulses of 0.5 Hz rTMS, or sham stimulation. EEGs were recorded before stimulation and within 1 min after rTMS or sham stimulation. Estimates of the EEG correlation dimension (D(2)) and power spectra were calculated. Results show that the D(2) reduced significantly after low-frequency rTMS, but not after sham stimulation. Mean absolute power (MAP) of the gamma band and relative power (RP) of the beta and gamma bands reduce markedly after low-frequency rTMS, but there are no changes with sham stimulation. These results indicate that low-frequency rTMS could affect cortical activities significantly, but effects were markedly different from those of high-frequency rTMS.     

Prefrontal cortical blood flow predicts response of depression to rTMS

Background

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for resistant major depressive disorder. The response rate of rTMS for depression is modest, motivating the search for biomarkers predictive of treatment response.

Methods

Thirteen patients (mean age 45 years, three males) with current major depression resistant to at least one antidepressant trial in the current episode were treated with a 25 day course of rTMS over the left dorsolateral prefrontal cortex (DLPFC). Resting state cerebral perfusion was measured prior to the first day of treatment and after the final day of treatment. Treatment response was measured using the Hamilton Depression Rating Scale - 24 Item (Ham-D). Baseline cerebral perfusion was compared in responders to non-responders. In addition, post-treatment cerebral perfusion was compared to pre-treatment in responders as well as in non-responders.

Results

Six individuals responded to rTMS. Responders had greater resting state blood flow in the left DLPFC (the target site) at baseline compared to non-responders. Non-responders showed greater baseline activity in the left medial frontal cortex. Neither group exhibited changes during treatment, nor did the combined group.

Limitations

This study suffers from low sample size and resulting small responder and non-responder subgroups. The sample was not balanced to gender. A normal control group was not included.

Conclusions

We believe this is the first study to compare pre-treatment brain perfusion patterns of depressed individuals who responded to rTMS to those who did not. Our results suggest stronger left DLPFC perfusion in responders and stronger medial prefrontal perfusion in non-responders both at baseline and post-treatment. These results await confirmation in a larger, prospective, placebo-controlled study.