The reduction in sexual behavior of adult female rats exposed to immune stress in the neonatal period is associated with reduced hypothalamic progesterone receptor expression.

PURPOSE: We examined the mechanism by which neonatal immune stress reduces the sexual behavior of female rats in adulthood. METHODS: Neonatal female rats were randomly divided into 3 groups: control (n = 11), postnatal day 10 lipopolysaccharide (PND10LPS) (n = 23), and PND25LPS (n = 11) groups, which received intraperitoneal injections of LPS (100 µg/kg) or saline on PND10 and 25. Daily inspections of the vaginal opening (VO) were performed from PND27 to PND37. Thereafter, the frequency of estrus was assessed for 15 days. Female rats (at 11-12 weeks of age) were placed in a cage with male rats, and their sexual behavior was monitored for 30 min. The hypothalamic mRNA expression levels of factors related to sexual behavior were examined via real-time PCR. RESULTS: VO occurred later and the frequency of estrus was lower in the PND10LPS group compared to the control group. The number of lordosis behaviors and the total number of mounts performed by male partners were lower in the PND10LPS and PND25LPS groups than in the control group. Acceptability: The lordosis quotient and lordosis rating were lower in the PND10LPS group than in the control group. Proceptive behavior: the number of ear wiggling events was lower in the PND10LPS group than in the other groups, and the number of hops/darts was lower in the PND10LPS group than in the control group. The hypothalamic mRNA expression level of progesterone receptors (PR)A + B was lower in the PND10LPS group than in the control group, and the hypothalamic PRB mRNA expression level was lower in the PND10LPS and PND25LPS groups than in the control group. CONCLUSION: Neonatal immune stress impeded sexual behavior and hypothalamic PR mRNA expression in female rats. Decreased progesterone activity in the hypothalamus might explain the reduction in sexual behavior seen in these rats.

Experiences With Aggressive Cardiac Rehabilitation in Pediatric Patients Receiving Mechanical Circulatory Supports.

Although some patients with fulminant myocarditis can be rescued owing to the improvements in mechanical circulatory support therapy, there are few reports providing evidence of cardiac rehabilitation during mechanical circulatory supports, particularly among pediatric patients. We treated two pediatric patients who underwent aggressive cardiac rehabilitation during mechanical support. Five days after the initiation of extracorporeal membrane oxygenation therapy aggressive cardiac rehabilitation was started in a 10-year-old girl with fulminant myocarditis. After explantation of the device, she was discharged on postoperative day 23. A 6-year-old girl with fulminant myocarditis started receiving cardiac rehabilitation two days after the initiation of an extracorporeal left ventricular assist device, despite having hemiplegia due to a recent broad stroke. She achieved an exercise capacity of supported walking for 280 meters after 127 days of cardiac rehabilitation and then went abroad to undergo heart transplantation when she was in the best physical condition possible. Early initiation of cardiac rehabilitation may be safe and effective for successful pediatric mechanical circulatory support therapy; this acts as a bridge to explantation or heart transplantation.

Upregulation of axonal HCN current by methylglyoxal: Potential association with diabetic polyneuropathy.

OBJECTIVE: To describe functional changes of axonal ion channels by a metabolic derivative of glucose, methylglyoxal (MGO), and its potential contribution to diabetic neuropathy. METHODS: (1) In wild-type male mice, multiple excitability measurements of sensory nerves were performed at baseline and 1week after serial administration of MGO (50mg/kg). (2) Excitability testing in patients with diabetic neuropathy (N=17) and healthy controls (N=12) were also conducted, and data were interpreted using mathematical modeling. RESULTS: In the animal study, there was a decrease in threshold changes by long hyperpolarization and in superexcitability after administration of MGO. In the preliminary human study, the threshold changes by long hyperpolarizing current were decreased in patients with diabetes. Mathematical modeling showed increased hyperpolarization-activated cation current (Ih) in the MGO-treated mice and in patients with diabetes. CONCLUSION: Ih was upregulated after MGO administration in normal mice. SIGNIFICANCE: MGO is associated with abnormal axonal excitability. Hyperexcitability in diabetic polyneuropathy may, at least in part, be caused by dysfunctional axonal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. A future study with a large sample size of the diabetic patients would clarify this hypothesis.

Effects of anesthetic agents on in vivo axonal HCN current in normal mice.

OBJECTIVE: The objective was to study the in vivo effects of anesthetic agents on peripheral nerve excitability. METHODS: Normal male mice were anesthetized by either isoflurane inhalation or a combination of medetomidine, midazolam, and butorphanol intraperitoneal injection ("triple agents"). Immediately after induction, the tail sensory nerve action potential was recorded and its excitability was monitored. RESULTS: Under both anesthetic protocols, there was an interval excitability change by long hyperpolarizing currents. There was greater threshold reduction approximately 30min post induction, in comparison to immediately post induction. Other excitability parameters were stable over time. Modeling suggested interval suppression of internodal H conductance or leak current. CONCLUSIONS: Anesthetic agents affected responses to long hyperpolarizing currents. SIGNIFICANCE: Axonal excitability during intraoperative monitoring may be affected by anesthetic agents. Interpretation of interval excitability changes under anesthesia requires caution, especially with long hyperpolarizing currents.

Constitutive activation of a CC-NB-LRR protein alters morphogenesis through the cytokinin pathway in Arabidopsis.

Possible links between plant defense responses and morphogenesis have been postulated, but their molecular nature remains unknown. Here, we introduce the Arabidopsis semi-dominant mutant uni-1D with morphological defects. UNI encodes a coiled-coil nucleotide-binding leucine-rich-repeat protein that belongs to the disease resistance (R) protein family involved in pathogen recognition. The uni-1D mutation causes the constitutive activation of the protein, which is stabilized by the RAR1 function in a similar way as in other R proteins. The uni-1D mutation induces the upregulation of the Pathogenesis-related gene via the accumulation of salicylic acid, and evokes some of the morphological defects through the accumulation of cytokinin. The rin4 knock-down mutation, which causes the constitutive activation of two R proteins, RPS2 and RPM1, induces an upregulation of cytokinin-responsive genes and morphological defects similar to the uni-1D mutation, indicating that the constitutive activation of some R proteins alters morphogenesis through the cytokinin pathway. From these data, we propose that the modification of the cytokinin pathway might be involved in some R protein-mediated responses.

Caenorhabditis elegans DAZ-1 is expressed in proliferating germ cells and directs proper nuclear organization and cytoplasmic core formation during oogenesis.

The deleted in azoospermia (DAZ) family genes encode potential RNA-binding proteins that are expressed exclusively in germ cells in a wide range of metazoans. We have previously shown that mutations in daz-1, the only DAZ family gene in Caenorhabditis elegans, cause pachytene stage arrest of female germ cells but do not affect spermatogenesis. In this study, we report that DAZ-1 protein is most abundantly expressed in proliferating female germ cells, in a manner independent of the GLP-1 signaling pathway. DAZ-1 is dispensable in males but it is expressed also in male mitotic germ cells. Detailed phenotypic analyses with fluorescence microscopy and transmission electron microscopy have revealed that loss of daz-1 function causes multiple abnormalities as early as the onset of meiotic prophase, which include aberrant chromatin structure, small nucleoli, absence of the cytoplasmic core, and precocious cellularization. Although the reduced size of nucleoli is indicative of a low translational activity in these cells, artificial repression of general translation in the germline does not phenocopy the daz-1 mutant. Thus, we propose that DAZ-1 in C. elegans plays essential roles in female premeiotic and early meiotic germ cells, probably via regulating the translational activity of specific target genes required for the progression of oogenesis.

The Mitotic Apparatus with Unusually Many Microtubules from Sea Urchin Eggs Treated by Hexyleneglycol: (microtubule/mitotic apparatus/granular material/sea urchin).

The effect of hexyleneglycol on the structure of the mitotic apparatus was studied by light and electron microscopies. By treating sea urchin eggs at prometaphase and metaphase with hexyleneglycol, the mitotic apparatus was found to become remarkably decorated with unusually many astral microtubules which were conspicuously uniform in length. These microtubules appeared to be associated with the granular materials which are most likely microtubule initiating sites or microtubule-organizing centers.

Studies on Unequal Cleavage in Sea Urchins II. Surface Differentiation and the Direction of Nuclear Migration: (sea urchin micromere/cortical differentiation/equal-unequal cleavage).

Cortical features of the meso- and macromeres differ from those of the micromeres in sea urchins. At the end of the 8-cell stage, the four animal cells have a continuous row of vesicles lining the free surface of the cell by transmission electron microscopy (TEM) and the nuclei and the resulting mitotic apparatuses (MA) remain at the cell centers and eventually divide equally into eight mesomeres. In the four vegetal cells, narrow gaps can be seen in the vesicular rows near the vegetal pole. The resting nuclei migrate to these gaps and on forming the spindles, they point directly to the gaps. The result is formation of vesicle-free micromeres and vesicle-covered macromeres by unequal divisions.