Mariko Itoh

Development of full-length Trk B-immunoreactive structures in the prefrontal and visual cortices of the macaque monkey

Distribution and morphological changes of cells containing the signal transducing neurotrophin receptor, full-length Trk B (fl-Trk B), were investigated in the prefrontal cortex (area FD) and the primary visual cortex (area OC) of the macaque monkey between embryonic day 140 and the adult stage. In area FD at the adult stage, fl-Trk B immunoreactivity was mainly observed in the pyramidal cells in layers II/III, V and VI. Small numbers of granule cells in layer IV were immunopositive. Bipolar and multipolar cells in layer II were rarely immunoreactive. At embryonic day 140, the number of fl-Trk B immunoreactive pyramidal cell was high, and gradually decreased until the adult stage. In layer IV, the number of fl-Trk B-ir cells was also high at embryonic day 140, and decreased remarkably from postnatal day 7 to the adult stage. On the other hand, in area OC at the adult stage, cells in layers II/III, IV, V and VI were fl-Trk B immunopositive. From embryonic day 140 until adulthood, the cells in layer IVc were fl-Trk B immunoreactive. The strongest fl-Trk B immunoreactivity in areas FD and OC occurred at postnatal month 6, coinciding with the time of the synapse overproduction. These findings suggest that ligands of fl-Trk B, such as BDNF and NT4/5 may be involved in the development and maintenance of the monkey cerebral cortices.

Lowering barometric pressure aggravates depression-like behavior in rats

Weather change has been known to influence the condition of patients with mood disorder. However, no animal studies have tested the influence of climatic factor on emotional impairment. In this study, we examined the effect of lowering barometric pressure (LP) in a climate-controlled room on immobility time in the forced swim test in rats, which is considered to be an index of behavioral despair (helplessness). When the rats were exposed to daily repeated forced swim, the immobility time gradually increased. This increment was inhibited by repeated administration of the antidepressant imipramine, suggesting that the immobility is an anxiety/depression-like behavior. LP exposure (20 hPa below the natural atmospheric pressure) further increased immobility time in rats submitted to repeated forced swim. In another series of experiments, we examined the effect of daily repeated LP exposure on the maintenance of immobility after withdrawal from 6-day repeated forced swim. When the rats were challenged with forced swim under natural atmospheric pressure on day 14 after the withdrawal, immobility time was significantly longer than in non-conditioned rats. These findings demonstrated that LP in the range of natural weather change augmented the depression-like behavior in rats.

Cellular localization of NGF and its receptors trkA and p75LNGFR in male reproductive organs of the Japanese monkey, Macaca fuscata fuscata

The actions of neurotropins are not restricted to the nervous system. Immunohistochemical methods were used in the present study to clarify distribution of nerve growth factor (NGF) and its receptors TrkA and p75LNGFR in excurrent ducts of the adult male Japanese monkey (Macaca fuscata fuscata). NGF was found in the seminal vesicle, epididymis, and testis, and has been thought to affect male reproductive functions. Leydig cells, Sertoli cells, and spermatogonia at various stages were positively stained for NGF, as well as for TrkA and p75LNGFR. Signals for these proteins were also found in epithelial cells and stromal tissues of the caudal epididymidis, as well as in the seminal vesicle. In the prostate, smooth muscle cells and basal cells were positively stained for NGF, TrkA, and p75LNGFR. The results were comparatively discussed.

Secretion of leptin throughout pregnancy and early postpartum period in Japanese monkeys: placenta as another potential source of leptin.

Leptin is one of the most important factors linking nutrition and reproduction. In the present study, plasma concentrations of leptin during pregnancy and early lactation in the Japanese monkey were determined. Plasma concentrations of gonadotropins, immunoreactive (ir-)inhibin, and steroid hormones were also measured. Plasma concentrations of leptin significantly increased during the second quarter of pregnancy and progressively elevated throughout pregnancy. During the fourth quarter of pregnancy, leptin levels reached up to 89 and 64 times of those during pre-pregancy and first quarter of pregnancy periods, respectively. After parturition, the circulating leptin level abruptly decreased. During the first 10 d of lactation, its average level decreased to the levels of the second quarter of pregnancy. Plasma ir-inhibin and estradiol-17β were elevated throughout the pregnancy and decreased after parturition, and both of them were positively correlated with leptin levels during the whole pregnancy and early lactation. Plasma concentrations of progesterone significantly increased during the first quarter of pregnancy and kept at a higher level compared with pre-pregnancy and sharply decreased after parturition. Placental homogenates contain a large amount of leptin protein. These results suggest that placenta secretes a large amount of leptin and may be another source of leptin during pregnancy in Japanese monkeys. In addition, high correlations among leptin, ir-inhibin, and estradiol-17β during these stages suggest that these hormones may have important regulating roles on leptin secretion during pregnancy in the Japanese monkey.

Inhibin B is the major form of inhibin secreted from testes in male Japanese macaques (Macaca fuscata)

In order to clarify the cellular source and forms of bioactive inhibin in male Japanese macaques (Macaca fuscata), circulating concentrations of inhibin A and B, and immunohistochemical localization of inhibin subunits in testis were studied. Plasma concentrations of testosterone were also measured. The present study showed that inhibin B was clearly detected in the plasma of male Japanese macaques. Moreover, concentrations of both inhibin B and testosterone during the breeding (mating) season were significantly higher than those of the non-breeding season. On the other hand, plasma inhibin A was detected neither during the breeding seasons nor during the non-breeding seasons. Positive stainings with α and βB subunit antibodies were observed in the Sertoli cells, however staining with βA subunit antibody was not observed in the testicular samples. These results indicate that inhibin B is the major circulating inhibin and probably secreting from Sertoli cells in male Japanese macaques.

Changes in Expression of Inhibin Subunits in the Cyclic Golden Hamster (Mesocricetus auratus) and the Regulation of Inhibin α Subunit Production by Luteinizing Hormone

In the present study, changes in localization of each inhibin subunit in the ovary were investigated during the estrous cycle of the golden hamster. The effect of LH surge on changes in localization in inhibin α subunit in the ovary was also investigated. Inhibin α subunit was localized in granulosa cells of various stages of follicles throughout the estrous cycle. Inhibin α subunit was also present in numerous interstitial cells on days 1 and 2 (day 1 = day of ovulation), but the number of positive interstitial cells was fewer on days 3 and almost disappeared on day 4 of the estrous cycle. Newly formed luteal cells were also positive for inhibin α subunit on days 1 and 2. On the other hand, positive reactions for inhibin βA and βB subunits were only present in the granulosa cells of healthy antral follicles. However, a positive reaction for inhibin βB subunit in peripheral mural granulosa cells disappeared on days 3 and 4 of the estrous cycle. Treatment with LHRH-AS at 1100 h on day 4 completely blocked the luteinizing hormone (LH) surge and ovulation, although relatively high concentrations of plasma follicle-stimulating hormone (FSH) were maintained throughout the experiment. There were few positive reactions for inhibin α subunit in theca and interstitial cells 24 hr after LHRH-AS injection. The effect of LHRH-AS treatment was blocked by a single injection of 10 IU human chorionic gonadotropin. These results suggest that the major source of dimeric inhibin in the cyclic hamster was granulosa cells of healthy antral follicles. Different distribution pattern of inhibin βA from βB subunits in large antral follicles on days 3 and 4 of the estrous cycle suggests different secretion patterns of inhibin A from B on these days. Furthermore, the LH surge may be an important factor to induce production of inhibin α subunit in interstitial cells of the cyclic hamster.

Low barometric pressure aggravates neuropathic pain in guinea pigs.

Several clinical studies have demonstrated a consistent relationship between changes in meteorological factors, particularly barometric pressure, and pain intensity in subjects with chronic pain. We have previously demonstrated that exposure to artificially low barometric pressure (LP) intensifies pain-related behaviors in rats with neuropathic pain. In the present study, guinea pigs with unilateral L5 spinal nerve ligation (SNL) were placed in a pressure-controlled chamber and subjected to LP of 10 or 27hPa below the ambient pressure. The SNL surgery led to increased hindpaw withdrawal frequencies to 34-, 59-, and 239-mN von Frey filaments (VFFs). When the SNL animals were subjected to both LP exposures consecutively, the hindpaw withdrawal frequencies further increased; the effect was most significant when the animals were exposed to LP 27hPa below ambient pressure. In contrast, no change was seen in a group of sham-operated control animals. These results indicate that fluctuations in LP within the range of natural weather patterns can potentiate neuropathic pain in guinea pigs.

Self-assembly formation of amphiphilic molecules mixed with photoreactive, aromatic unsaturated-acids: examination by light scattering

Light scattering measurement was carried out for aqueous solutions of amphiphilic molecules mixed with aromatic unsaturated carboxylic acids. Their structures are discussed according to sizes of molecular assemblies evaluated. In aqueous solutions of hexadecyltrimethylammonium hydroxide with 2-indenecarboxylic acid, short rodlike micelles were formed on mixing at a ratio of 1∶1. Particles in aqueous solutions of dodecyldimethylamine oxide and cinnamic acid varied from micelles to vesicles with increasing cinnamic acid concentration. The structures were related to the effective photocyclodimerization of olefins and the stereochemical selectivity of cyclodimers.

Regulations of gonadotropin secretion by circulating inhibin, estradiol, and progesterone in cyclic hamsters

The physiological importance of gonadal hormones in feedback control of gonadotropin secretion during the estrous cycle in golden hamsters was investigated with immunoneutralization methods. Anti-inhibin serum (inhibin-AS) treatment always induced a drastic increase in follicle-stimulating hormone (FSH) secretion and occasionally raised luteinizing hormone (LH) secretion. Anti-estradiol-17β serum (estradiol-AS) treatment increased LH secretion typically. Although estradiol-AS elevated FSH secretion occasionally, the elevation was much less than that by inhibin-AS. Plasma FSH reached ovariectomized levels by a synergistic effect of both antisera. Elevated plasma LH with both antisera was much less pronounced than in ovariectomized animals. Plasma LH increased dramatically to the levels in the ovariectomized group when antibody against progesterone (progesterone-AB) was given together with inhibin-AS and estradiol-AS, although progesterone-monoclonal antibody alone did not alter plasma gonadotropin levels. These results indicate that in hamsters FSH secretion is mainly regulated by inhibin and LH secretion is regulated by estradiol-17β and progesterone during the estrous cycle.The physiological importance of gonadal hormones in feedback control of gonadotropin secretion during the estrous cycle in golden hamsters was investigated with immunoneutralization methods. Anti-inhibin serum (inhibin-AS) treatment always induced a drastic increase in follicle-stimulating hormone (FSH) secretion and occasionally raised luteinizing hormone (LH) secretion. Anti-estradiol-17beta serum (estradiol-AS) treatment increased LH secretion typically. Although estradiol-AS elevated FSH secretion occasionally, the elevation was much less than that by inhibin-AS. Plasma FSH reached ovariectomized levels by a synergistic effect of both antisera. Elevated plasma LH with both antisera was much less pronounced than in ovariectomized animals. Plasma LH increased dramatically to the levels in the ovariectomized group when antibody against progesterone (progesterone-AB) was given together with inhibin-AS and estradiol-AS, although progesterone-monoclonal antibody alone did not alter plasma gonadotropin levels. These results indicate that in hamsters FSH secretion is mainly regulated by inhibin and LH secretion is regulated by estradiol-17beta and progesterone during the estrous cycle.

Organized photodimerization of unsaturated carboxylates. Selectivity control by normal and reversed micelles

Aromatic unsaturated carboxylates such as cinnamate and 2-indenecarboxylate form, in the presence of long-chain alkylammonium ion, short rod-like micelles with an aggregation number of an order of 103 in water and premicelle aggregates including 2–3 surfactant molecules in carbon tetrachloride. It was found that these aggregates undergo efficient and stereoselective photodimerizations. Photoreactions in aqueous rod-like micellar solutions resulted in the predominant formation of anti-head-to-head dimers (anti-HH), while the reaction in small aggregated premicelles yielded thermodynamically least stable syn-head-to-head dimers (syn-HH). The addition of a small amount of methanol to the premicelle aggregate shifted the major product from syn-HH to anti-HH. Control experiments showed that the photoreaction of the corresponding methyl ester afforded mixtures of four isomeric dimers, syn- and anti-HH and HT (head-to-tail), of statistical distribution. These stereochemical selectivities are discussed in terms of the organized olefin orientation and correlated to the results of light scattering and NMR probe techniques.