Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation

Presenilin 1 (PS1) regulates environmental enrichment (EE)-mediated neural progenitor cell (NPC) proliferation and neurogenesis in the adult hippocampus. We now report that transgenic mice that ubiquitously express human PS1 variants linked to early-onset familial Alzheimer's disease (FAD) neither exhibit EE-induced proliferation, nor neuronal lineage commitment of NPCs. Remarkably, the proliferation and differentiation of cultured NPCs from standard-housed mice expressing wild-type PS1 or PS1 variants are indistinguishable. On the other hand, wild-type NPCs cocultured with primary microglia from mice expressing PS1 variants exhibit impaired proliferation and neuronal lineage commitment, phenotypes that are recapitulated with mutant microglia conditioned media in which we detect altered levels of selected soluble signaling factors. These findings lead us to conclude that factors secreted from microglia play a central role in modulating hippocampal neurogenesis, and argue for non-cell-autonomous mechanisms that govern FAD-linked PS1-mediated impairments in adult hippocampal neurogenesis.     

The progesterone challenge: steroid hormone changes following a simulated territorial intrusion in female Peromyscus californicus

There is a growing body of evidence that the rapid but transient increase in male androgens, particularly testosterone (T), following a single social encounter such as a territorial intrusion occurs in a wide array of vertebrate taxa. Yet, this phenomenon, often called the Challenge Hypothesis, has rarely been investigated in females. Moreover, when studying male challenge effects, researchers have rarely investigated other hormones that can be important to the expression of aggression, such as progesterone (P4) and estradiol (E2). We conducted 10-min aggression trials using the resident-intruder paradigm in cycling female California mice, Peromyscus californicus, a species in which both sexes show territorial behavior. By comparing the hormone levels of test females to control females, we found a decrease in P(4) and the P4/T ratio, but no change in T, E2, corticosterone, E2/P4, or E2/T. Interestingly, these hormone changes were observed even when the resident was not aggressive toward the intruder, suggesting that the stimulus cueing the hormone changes was the mere presence of the intruder and not the amount of aggression displayed by the resident. Generally, T has a positive relationship with aggression, whereas P4 inhibits male and nonmaternal female aggression. Thus, decreasing the P4/T ratio following an encounter may serve to increase future aggression in females. These results suggest that females may use different hormonal mechanisms than do males to mediate aggression in a challenge situation.     

Circular excision of hemangioma and purse-string closure: the smallest possible scar

Localized cutaneous infantile hemangioma acts like a tissue expander. This rapidly growing tumor can destroy elastic fibers or cause ulceration resulting in telangiectases, cutaneous laxity, scarring, and fibrofatty residuum. Although surgeons may dispute indications and timing, most would agree that the scar of resection should be minimized. For this reason, circular excision and purse-string closure is particularly applicable for hemangioma at any stage of its evolution. The purposes of this study were to: (1) analyze the results of circular excision/purse-string closure in all three phases of the life cycle of hemangioma; (2) quantify dimensional changes after resection; and (3) compare the scars after theoretical single-stage lenticular excision with those after staged circular excision/purse-string closure. The authors retrospectively analyzed their experience in 25 children with localized hemangioma who underwent circular excision/purse-string closure from 1997 to 2000. Each hemangioma was measured preoperatively and the scars were measured at most recent follow-up (minimum, 6 months). Preoperative and postoperative dimensions were analyzed using SPSS statistical software. The study included 22 girls and three boys, with an average time to follow-up evaluation of 13.1 months. Twenty-one lesions were in the face and scalp, and five were in the extremity. Five tumors were resected in the proliferative phase (either because of ulceration, bleeding, or visual complications) and 21 were excised in the involuting or involuted phase. Six patients had a second-stage procedure: three had another circular excision and three had later lenticular excision. After single circular excision/purse-string closure, the mean long-axial diameter (length) decreased by 45 percent, the mean short-axial width (width) decreased by 73 percent, and the mean scar area was only 15 percent of the original area. All these differences were statistically significant (p = 0.001). The average width/length ratio decreased by 50 percent, indicating a tendency for scars to linearize. There was no difference in linearization for the three phases of hemangioma (p > 0.05); extremity scars became more linear that those on the face (p = 0.01). The authors devised a formula for scar length after lenticular excision/linear closure, assuming a conventional excisional ratio of 3:1 for a circular lesion. Using this equation, the authors predicted that mean scar length after circular excision, followed by lenticular excision, would be 72 percent shorter than the calculated scar that would result from conventional lenticular excision. In three patients who underwent this two-stage approach, the resultant scar was 69 percent shorter. Circular excision of hemangioma and purse-string closure reduces both the longitudinal and transverse dimensions and converts a large circular lesion into a small ellipsoid scar. If subsequent revision to a linear scar is desirable, its length will be the same or slightly less than the diameter of the original lesion. No other excision and closure technique results in a smaller scar. Another advantage of this method is minimal distortion of surrounding structures.     

A 3347-locus genetic recombination map of sequence-tagged sites reveals features of genome organization, transmission and evolution of cotton (Gossypium)

We report genetic maps for diploid (D) and tetraploid (AtDt) Gossypium genomes composed of sequence-tagged sites (STS) that foster structural, functional, and evolutionary genomic studies. The maps include, respectively, 2584 loci at 1.72-cM ( approximately 600 kb) intervals based on 2007 probes (AtDt) and 763 loci at 1.96-cM ( approximately 500 kb) intervals detected by 662 probes (D). Both diploid and tetraploid cottons exhibit negative crossover interference; i.e., double recombinants are unexpectedly abundant. We found no major structural changes between Dt and D chromosomes, but confirmed two reciprocal translocations between At chromosomes and several inversions. Concentrations of probes in corresponding regions of the various genomes may represent centromeres, while genome-specific concentrations may represent heterochromatin. Locus duplication patterns reveal all 13 expected homeologous chromosome sets and lend new support to the possibility that a more ancient polyploidization event may have predated the A-D divergence of 6-11 million years ago. Identification of SSRs within 312 RFLP sequences plus direct mapping of 124 SSRs and exploration for CAPS and SNPs illustrate the "portability" of these STS loci across populations and detection systems useful for marker-assisted improvement of the world's leading fiber crop. These data provide new insights into polyploid evolution and represent a foundation for assembly of a finished sequence of the cotton genome.     

Opposing hormonal mechanisms of aggression revealed through short-lived testosterone manipulations and multiple winning experiences

Territorial aggression is influenced by many social and environmental factors. Since aggression is a costly behavior, individuals should account for multiple factors such as population density or reproductive status before engaging in aggression. Previous work has shown that male California mice (Peromyscus californicus) respond to winning aggressive encounters by initiating aggression more quickly in future encounters, and we investigated the physiological basis for this effect. We found that injections that produced a transient increase in testosterone (T) following an aggressive encounter caused males to behave more aggressively in an encounter the following day. Experience alone was not enough to change aggression, as males treated with saline injections showed no change in aggression. The effect of T injections on aggression was androgen-based, as the inhibition of aromatase did not block the T injections from increasing aggression. Aromatase inhibition did, however, increase aggression in the initial aggression tests (before application of T or saline injections), and aromatase activity in the bed nucleus of the stria terminalis (BNST) was negatively correlated with aggression. A previous study suggested that aromatase activity in the BNST decreases after males become fathers. Thus, distinct neuroendocrine mechanisms allow male California mice to adjust aggressive behavior in response to changes in social and reproductive status.     

Testosterone, paternal behavior, and aggression in the monogamous California mouse (Peromyscus californicus)

Testosterone (T) mediates a trade-off, or negative correlation, between paternal behavior and aggression in several seasonally breeding avian species. However, the presence or absence of a T-mediated trade-off in mammals has received less attention. We examined the relationship between paternal behavior and territorial aggression in the biparental California mouse, Peromyscus californicus. In contrast to seasonally breeding birds, T maintains paternal behavior in this year-round territorial species. Castration reduced paternal behavior, whereas T replacement maintained high levels of paternal behavior. We hypothesize that T is aromatized in the brain to estradiol, which in turn stimulates paternal behavior. In contrast to paternal behavior, aggressive behavior was not reduced by castration. Interestingly, only sham males showed an increase in aggression across three aggression tests, while no change was detected in castrated or T-replacement males. Overall, trade-offs between aggression and paternal behavior do not appear to occur in this species. Measures of paternal behavior and aggression in a correlational experiment were actually positively correlated. Our data suggest that it may be worth reexamining the role that T plays in regulating mammalian paternal behavior.     

A comparison of scent marking between a monogamous and promiscuous species of peromyscus: pair bonded males do not advertise to novel females

Scent marking can provide behavioral and physiological information including territory ownership and mate advertisement. It is unknown how mating status and pair cohabitation influence marking by males from different social systems. We compared the highly territorial and monogamous California mouse (Peromyscus californicus) to the less territorial and promiscuous white-footed mouse (P. leucopus). Single and mated males of both species were assigned to one of the following arenas lined with filter paper: control (unscented arena), male scented (previously scent-marked by a male conspecific), or females present (containing females in small cages). As expected, the territorial P. californicus scent marked and overmarked an unfamiliar male conspecific's scent marks more frequently than P. leucopus. Species differences in responses to novel females were also found based on mating status. The presence of unfamiliar females failed to induce changes in scent marking in pair bonded P. californicus even though virgin males increased marking behavior. Pair bonding appears to reduce male advertisement for novel females. This is in contrast to P. leucopus males that continue to advertise regardless of mating status. Our data suggest that communication through scent-marking can diverge significantly between species based on mating system and that there are physiological mechanisms that can inhibit responsiveness of males to female cues.     

A positive Link Between Male Testosterone and Spacing Behavior in Pair‐Bonded California Mice

The effects of testosterone (T) on male sexual behavior are well established, but its roles in several associated social behaviors such as pair‐bonding and paternal behavior are diverse. Recently, we reported that male T in response to pairing with a female predicts future paternal behavior in the monogamous and biparental California mouse (Peromyscus californicus). Here, we examined whether T in response to pairing is also associated with spacing behavior between mates under laboratory conditions and if these behavioral patterns are continued during pup care. Pairs of California mice were observed throughout their pair bond before and again after pups were born. We found that males with higher T post‐pairing remained closer to their mates in the weeks before pups were born, and pairs with higher proximity measures during the pair bond spent more time caring for pups together. Overall, these results suggest a similar mechanism for spacing behavior across distinct phases of the pair bond.