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M Nishizuka

Publications and source records attributed to M Nishizuka.

33 records · Page 2Linked to original sources

Medial preoptic islands in the rat brain: electron microscopic evidence for intrinsic synapses.

Neurons intrinsic to the preoptic area might participate in the control of neuroendocrine or behavioral events. To determine their existence and features, we deafferented the preoptic area of female rats, using completely circumscribing cuts with a Halasz knife. Despite obvious signs of degeneration of synapses originating from nerve cell bodies outside the preoptic island, some synapses survived complete deafferentation. We saw synaptic contacts not only on the neuronal cell body, but also on the dendritic shaft and spine. There were no peculiar morphological features, as might suggest unique physiologic functions of these intrinsic synapses. The prominence of intrinsic synapses in the preoptic area suggests that, in addition to hormone effects on preoptic neurons, and long ascending afferents, intrinsic synapses might play significant roles in neuroendocrine controls.

Animals↗

Intrinsic connections in the medial amygdala as revealed by complete deafferentation.

Using a newly designed knife, the medial amygdala of rats was completely deafferented to exclude the synapses of the afferents coming from the outside of the medial amygdaloid nucleus (MAN). Semiquantitative analysis by electron microscopy showed that the number of the intact dendritic synapses per unit neuropil area of the MAN of the islands was markedly reduced to about one-third of that of the controls. These intact synapses appeared to be intrinsic or of local origin. In contrast, degenerating synapses, two-thirds of the dendritic synapses in the MAN, were considered as synapses with the fibers from outside the islands.

Afferent Pathways↗

Male-female differences in the intra-amygdaloid input to the medial amygdala.

Following lesion of the posterior cortical nucleus of the amygdala (PCAN), the number of degenerating axon terminals and alterations of synaptic pattern were studied in the molecular layer (ML) of the medial nucleus of the amygdala (MAN) of male and female rats. Semiquantitative analyses by electron microscopy indicated that, 1 and 2 days after the lesion, the number of degenerating terminals in the ventral ML of male rats was statistically greater than that of female rats. Ten days after the operation, intact synapses remaining on dendritic shafts of the medial ML and those on dendritic spines of the ventral ML of male rats significantly decreased in number, compared with unoperated controls. On the other hand, no significant reduction was noted in synapses of the lesioned female rats killed 10 days after the operation. Thus, the number of axon terminals in the male ML originating from the lesioned area was greater than that of the female ML. The number of synapses in the ML of unoperated male rats was statistically greater than that of unoperated females. However, these sex differences in synaptic number became undetectable 10 days after the operation. These findings provide morphological evidence indicating that the fibers from and/or through the PCAN participate in emergence of synaptic sexual dimorphism in the ML of the MAN.

Afferent Pathways↗

Regional difference in sexually dimorphic synaptic organization of the medial amygdala.

The existence of sexual dimorphism in synaptic pattern is demonstrated in the molecular layer of the medial nucleus of the rat amygdala by semiquantitative electron microscopic analysis on synaptic density. Sex difference in synaptic number was found in dendritic shaft synapses in the medial part of the molecular layer, whereas the difference occurred in dendrite spine synapses in the ventral molecular layer. The present study also provides evidence for the involvement of sex steroids in the development of sexually dimorphic neuronal circuitry in the molecular layer.

Amygdala↗

Sexual difference in nuclear volume and its ontogeny in the rat amygdala.

Nuclear volume of the medial and lateral nuclei of the amygdala was investigated in male and female rats. The volume of the medial nucleus in the adult male rat was significantly greater than that of the female rat. Treatment of female rats with estrogen for the first 30 days of postnatal life increased the nuclear size, and the volume became comparable to that of the males. Although there was no significant difference in volume of this nucleus between male and female rats from days 1 (day of birth) to 11, the difference became evident at day 21, and thereafter it persisted. In contrast, the nuclear volume of the lateral nucleus was not different between the two sexes. Estrogen treatment did not influence the volume of the lateral nucleus in the female animals. These data indicate that the nuclear volume is sexually different in the medial nucleus of the amygdala, and its differentiation occurs during the early postnatal period under the influence of the organizational action of sex steroids.

Amygdala↗

Synapse formation in response to estrogen in the medial amygdala developing in the eye.

Medial amygdaloid tissue, taken from female rats immediately after birth, was transplanted into the anterior chamber of the eye in adult ovariectomized host rats in order to elucidate the influence of estrogen on synapse formation without contribution of neural afferents. After injections of estradiol benzoate or oil vehicle to the hosts for 20 successive days, the grafts were processed for semiquantitative electron microscopic study to examine synaptic density in the neuropil. The number of synapses on dendritic shafts vs. dendritic spines was not significantly different in the control group. In contrast, in the grafts exposed to estrogen, shaft synapses occurred more frequently than spine synapses. Synaptic density on shafts was significantly greater in these grafts than that in the controls, although the density on spines did not differ between the two groups. These data show that estrogen affects the medial amygdaloid neurons themselves and specifically facilitates the formation of dendritic shaft synapses in oculo. Our previous report raises the possibility that the specific increase of shaft synapses induced by sex steroids is involved in the process of sexual differentiation of neuronal networks from the inherently feminine pattern to the masculine pattern in the medial amygdala. Therefore, the present findings may provide evidence that sexual differentiation triggered by sex steroids is accomplished by intrinsic factors in the neurons of the medial amygdala.

Amygdala↗

Organizational action of estrogen on synaptic pattern in the amygdala: implications for sexual differentiation of the brain.

Estrogen markedly promotes the specific formation of dendritic shaft synapses in the medial amygdaloid nucleus (AMN) of the rat when given in early postnatal days. The high incidence of this type of synapse permanently persists until sacrifice at adult ages. The data provide evidence for the synaptic plasticity of the developing amygdala to estrogen and suggest a possible morphological mechanism for sexual differentiation of the brain.

Aging↗

Topography of the dopamine neurons in the arcuate nucleus of the mouse hypothalamus.

The distribution of the dopamine (DA) cell bodies was elucidated within the mouse arcuate nucleus by fluorescence histochemistry. The arcuate nucleus was divided into five regions; heterogeneity in distribution and different amounts of DA among the regional areas were demonstrated. The DA cell bodies containing a large amount of DA, observable even in the arcuate nucleus of the intact mice, distributed in the medial areas of the anterio-central and the middle-central regions and in the dorsal area of the posterior-central region. On the other hand, those containing probably as small amount of DA distributed in the medial area of the rostral region and in the ventral areas of the anterior-central and middle-central regions. They were not observed in the intact mice, but found in the mice treated with nialamide plus alpha-methyldopa. No DA cells were found in the caudal region.

Animals↗

The neurons containing dense core vesicles in the mouse hypothalamic arcuate nucleus: distribution and influence of ovarian activity.

The hypothalamic arcuate nucleus (ARC) was electron microscopically studied in diestrous (D) and estrous (E) mice, and mice ovariectomized (OX) 3 weeks before. In the middle region of the ARC (mARC), the number of dense core vesicles (DCVs) appearing in a section of each neuronal perikaryon was examined, and the location of the neurons containing DCVs was mapped. About 10% of the neurons in the mARC contained many (5 or more) DVCs in the perikarya in a section. These neurons mainly localized in the ventromedial portion of the mARC, which shows that the cytoarchitecture of the mouse ARC is heterogeneous. The localization and the frequency of these neurons were not influenced by the variance of ovarian activity. A DCV was composed of an electron-dense core and a membrane halo, and was likely to be formed in the cisternae of the Golgi apparatus. The size of DCVs was estimated at 100 nm as the median diameter and was stable independent of the ovarian activity. However, the formation of DCVs was likely influenced by the ovarian activity, because DCVs in D mice were more intimately associated with the Golgi apparatus than in E or OX mice. In the neuronal perikarya of the ventromedial portion of the mARC, Nissl bodies developed in OX mice and nucleolus-like bodies developed in E mice. These results suggest that the neurons of the ventromedial portion of the mARC change their function according to the variance of ovarian activity and, therefore, are involved in the estrogen feedback mechanism.

Animals↗

Topography of the neurons responding to estrogen in the hypothalamic arcuate nucleus of immature female mice.

The neurons in the hypothalamic arcuate nucleus (ARC) of 20-day-old female mice were examined by electron microscopy. The administration of estradiol-17 beta during 20 days from the day of birth resulted in the increase of dense-core vesicles (DCVs) in some neuronal perikarya of the middle region of the ARC (middle ARC), while, in the posterior region of the ARC (posterior ARC), the increase of DCVs was less marked. Topographical studies revealed that the neuronal perikarya containing few DCVs were assembled in the ventromedial area of the middle ARC in both control mice and mice given estrogen. Those containing 5 or more DCVs were found predominantly in the ventromedial area of the middle ARC in mice given estrogen. In the posterior ARC, however, the neuronal perikarya containing DCVs seemed to be scattered. The distribution patterns of the diameter of DCVs were significantly different between control mice and mice given estrogen. The administration of estrogen seem to bring about the enlargement in the size of DCVs. These results indicate that the neurons responding to estrogen are present in the ventromedial area of the middle ARC, and suggest that this area is a significant focus in estrogen feedback mechanisms.

Animals↗

Additional effects of postpuberal estrogen injections on the vaginal epithelium in neonatally estrogenized mice.

In the ovariectomized mice given 10 injections of 100 micrograms 17 beta-estradiol at intervals of 2 weeks from 60 days of age, the vaginal epithelium was atrophic when killed more than 2 months after the last injection. If mice given 3 daily injections of 20 micrograms 17 beta-estradiol from the day of birth were similarly treated with estradiol after postpuberal ovariectomy, the vaginal epithelium was stratified and hyperplastic at autopsy performed more than 2 months later. These changes in the epithelium persisted for at least 30 days after transplantation of the vaginae to normal ovariectomized hosts. Neonatal treatments only did not produce such persistent vaginal changes. In view of these results, additional effects of neonatal and postpuberal injections of estrogen on the vaginal epithelium are evident. However, effects of such neonatal and postpuberal injections of estrogen might be transient on the uterine epithelium, since abnormal proliferation was not observed in it.

Age Factors↗

Neuropharmacological study on the induction of hypothalamic masculinization in female mice.

82% of female mice, that had received a single injection of 50 mug testosterone propionate (TP) at 4 days of age, became persistent estrous by 90 days. If 50 mug pentobarbital or 10 mug reserpine was given simultaneously with TP, the incidence of hypothalamic masculinization (persistent estrus (PE) and polyfollicular ovaries lacking corpora lutea) at 90 days dropped to 33 and 30%, respectively. Phenoxybenzamine (50 mug) also decreased the incidence of PE to 20 and 30% at 60 and 90 days of age, respectively. However, propranolol failed to nullify the masculinization caused by TP. These results seem to suggest that a monoaminergic mechanism is involved in the hypothalamic masculinization of neonatal mice.

Animals↗