Anatomical characterization of the neuropeptide S system in the mouse brain by in situ hybridization and immunohistochemistry

Neuropeptide S (NPS) is the endogenous ligand for GPR154, now referred to as neuropeptide S receptor (NPSR). Physiologically, NPS has been characterized as a modulator of arousal and has been shown to produce anxiolytic‐like effects in rodents. Neuroanatomical analysis in the rat revealed that the NPS precursor mRNA is strongly expressed in the brainstem in only three distinct regions: the locus coeruleus area, the principal sensory trigeminal nucleus, and the lateral parabrachial nucleus. NPSR mRNA expression in the rat is widely distributed, with the strongest expression in the olfactory nuclei, amygdala, subiculum, and some cortical structures, as well as various thalamic and hypothalamic regions. Here we report a comprehensive map of NPS precursor and receptor mRNA expression in the mouse brain. NPS precursor mRNA is only expressed in two regions in the mouse brainstem: the Kölliker‐Fuse nucleus and the pericoerulear area. Strong NPSR mRNA expression was found in the dorsal endopiriform nucleus, the intra‐midline thalamic and hypothalamic regions, the basolateral amgydala, the subiculum, and various cortical regions. In order to elucidate projections from NPS‐producing nuclei in the brainstem to NPSR‐expressing structures throughout the brain, we performed immunohistochemical analysis in the mouse brain by using two polyclonal anti‐NPS antisera. The distribution of NPS‐immunopositive fibers overlaps well with NPSR mRNA expression in thalamic and hypothalamic regions. Mismatches between NPSR expression and NPS‐immunoreactive fiber staining were observed in hippocampal, olfactory, and cortical regions. These data demonstrate that the distribution pattern of the central NPS system is only partially conserved between mice and rats. J. Comp. Neurol. 519:1867–1893, 2011. © 2011 Wiley‐Liss, Inc.     

鼠疫耶尔森菌pgm位点及其侧翼序列遗传变异的比较分析

目的研究鼠疫耶尔森菌中国自然分离株pgm位点及其侧翼序列的变异,了解不同疫源地菌株间的毒力差异,为鼠疫防治提供帮助。方法比较分析现有4株菌的pgm位点及其侧翼序列的变异,采用PCR、等位基因特异性PCR扩增260株中国自然分离株和7株假结核耶尔森菌。结果除锡林郭勒高原型和青海田鼠型菌株外,其他菌株均缺失了YPl666的70～87bp之间的18bp碱基。1406bp处T的缺失仅存在于东方型菌株中。北天山东段型及西段A、B型,锡林郭勒高原型,青海田鼠型菌株的pgm位点下游都没有IS100插入;锡林郭勒高原型和青海田鼠型菌株的色素沉着区有1个IS285插入,在其下游3kb区域还有1个IS100插入。冈底斯山型和昆仑山A、B型菌株的pgm位点上游侧翼区与其他菌株不同。36株菌的pgm位点缺失,缺失的菌株主要集中在鄂尔多斯高原型,松辽平原B型,昆仑山A、B型4种生态型菌株中。结论北天山东段型及西段A、B型,锡林郭勒高原型,青海田鼠型菌株是中国鼠疫耶尔森菌中比较古老的菌株。锡林郭勒高原型和青海田鼠型菌株是一个独特的分支,建议归为第4个生物型——田鼠型。北天山东段型及西段A、B型,锡林郭勒高原型,青海田鼠型菌株的pgm位点,由于在其下游没有IS100插入,所以稳定、不易缺失。pgm位点及其侧翼序列的变异与菌株的生物型、自然疫源地和生态型都具有一定的相关性。     

Sex differences in circadian timing systems: Implications for disease

Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic–pituitary–gonadal axis (HPG), the hypothalamic–adrenal–pituitary (HPA) axis, and sleep–arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.     

Behavioral development in mice: Effects of maternal environment and the albino locus

We examined the interaction of the albino locus with the maternal environment on the behavioral development of two coisogenic strains of mice. Subjects of the pigmented C57BL/6 strain (=B6^+/+) and of the albino C57BL/6^c2J strain (=B6^c/c) were either fostered by a mother of their own strain or cross-fostered at birth to an F₁ hybrid dam. They were compared for the amount and daily distribution of activity displayed during 48 h in a seminatural device at weaning and when 75 days old. Food hoarding in the nest and food consumption at the food-search place were also recorded in adult subjects. When animals were fostered by a mother of their own strain, albino mice were more active and less nocturnal than pigmented mice at both ages. They hoarded less food in the nest and ate more at the food-search place. Most of these differences disappeared when both strains were fostered by an F₁ dam. The amount of activity displayed during 48 h increased between 21 and 75 days of age. This increase was affected by cross-fostering to an F₁ dam in B6^c/c mice only. The developmental pattern of daily distribution of activity was changed by F₁ dams in B6^+/+ mice only. Whereas these influences of F₁ dams produced subjects resembling the mother's phenotypic score, maternal effects on hoarding behavior in B6^c/c mice produced subjects which did not resemble their foster mother. The results are discussed in terms of different possible ways of hereditary transmission of behavior and some methodological consequences are emphasized.     

Vibrissectomy induced changes in GAP-43 immunoreactivity in the adult rat barrel cortex.

Within the rat primary somatosensory cortex, neurons responding principally to movement of each individual mystacial vibrissa are grouped together in structures termed barrels. Previous studies have examined changes in the area of cortex showing increased 2-deoxyglucose uptake in response to vibrissal stimulation. These studies have shown that chronic removal of all but the central (C3) vibrissa in adult rats induces an enlarged representation of the remaining C3 barrel in the contralateral cortex. This increase is prevented by cortical norepinephrine depletion. The major question raised by such studies is whether such plasticity is due to structural rearrangement or unmasking of otherwise silent synapses. In this study, antibodies to GAP-43, a presynaptic protein whose synthesis is related to neuronal development and regeneration, were used to investigate this issue. In adult rat brain, tangential sections through layer IV of the barrel receptor field normally show moderate levels of GAP-43 immunoreactivity (GAP-IR) in the inter-barrel septa and low levels within the barrels themselves. The present study examined changes in the pattern of GAP-IR from 1 to 8 weeks after vibrissectomy with sparing of C3 as an index of possible physical reorganization of cortical circuits. Quantitative analysis of the cortices of animals with unilateral vibrissectomy with sparing of C3 showed that the area of low GAP-IR within the barrels surrounding C3 was decreased at 1 week (8.4% shrinkage; P less than 0.01) and 8 weeks (12.0% shrinkage; P less than 0.015), relative to the cortex ipsilateral to the surgery. Both bilateral vibrissectomy with sparing of C3 and ibotenic acid lesions of the ventrobasal thalamus produced similar results. Some evidence was also seen that the area of low GAP-IR in the C3 barrel shrank to a similar degree after such manipulations. Cortical norepinephrine depletion had no apparent effect on vibrissectomy-induced GAP-IR changes. These results suggest that removal of vibrissal input to the adult rat barrel cortex produces transynaptic induction of axonal sprouting within the barrel cortex.     

Divergent axon collaterals of rat locu Demonstration by a fluorescent double labeling technique

The distribution of the noradrenaline-containing neurons of the rat locus coeruleus has been investigated with retrograde labeling techniques using two different fluorescent tracers. Injections were placed in the prefrontal cortex, the striatum, the thalamus, the hippocampus, the cerebellar cortex and the lumbar spinal cord.No evidence for locus coeruleus projections to the striatum was found. Injections in the cortex, thalamus and hippocampus revealed not only ipsilateral but also contralateral labeling of cells in the locus coeruleus. Following unilateral or bilateral homo- or heterotopic injections of the two tracers several cells of the locus coeruleus were double labeled. Combined injections of the two fluorophores in any of these forebrain areas and in the spinal cord also produced double labeled cells. The majority of double labeled cells was located in an area between the ventral and the dorsal parts of the locus coeruleus.These results indicate that individual neurons of the locus coeruleus have the possibility to influence adrenergic receptors at remote areas in the central nervous system.     

Destruction of noradrenergic cell bodies by intracerebral 6-hydroxydopamine in the newborn rat

Intracerebral injections of 6-hydroxydopamine directly in the nucleus locus coeruleus were performed in 4-day-old rats. The effects of such treatment on the subsequent development of this nucleus were analyzed and compared to those obtained in vehicle-injected age-paired controls. The 3 histological techniques used (Nissl, Glenner reaction, and histochemical fluorescence) indicated in the experimental group a progressive disappearance of the coerulean perikarya within 7 days postinjection. This lesion was permanent and did not induce any noradrenergic sprouting.     

Pharmacokinetics of theophylline in relation to increased pain sensitivity in the rat

In the rat, theophylline increases, in proportion to dose, the sensitivity to painful stimulation. A study of the pharmacological registration of this property combined with the determination of drug levels in plasma indicated that theophylline behaves according to a two-compartment open model. By relating the pharmacological activities to the drug level data using different pharmacokinetic types of calculation, it was concluded that the site of action of theophylline in the central nervous system lies closer to the central (plasma) compartment than to the peripheral one. The registered pharmacological effects of theophylline are thus directly reflected by the plasma concentration of this drug.