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I Tooyama

Publications and source records attributed to I Tooyama.

At least 73 records · Page 4Linked to original sources
PubMed1995

Regulation of neuronal nitric oxide synthase in rat adrenal medulla.

Neuronal nitric oxide synthase (nNOS) has been suggested to be involved in cardiovascular homeostasis. We studied the regulation of nNOS expression, determining nNOS mRNA expression levels in various tissues in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We also investigated the effects of antihypertensive treatment with the angiotensin II antagonist hydralazine or reserpine on nNOS mRNA expression. The expression levels of nNOS mRNA and nNOS protein were determined by Northern and Western blot analysis, respectively. NADPH-diaphorase histochemistry was used to identify cells in the adrenal medulla that expressed nNOS. No significant differences in expression levels in SHR and WKY were observed in the cerebellum and brain stem. nNOS mRNA expression levels in the decapsular portion of the adrenal gland were developmentally modulated and in a 24-week-old WKY were 2.5 times higher than in an age-matched SHR. This reduced expression of nNOS mRNA in the decapsular portion of the adrenal gland of SHR seemed to be a result of hypertension in the SHR, because administration of either an angiotensin II antagonist (TCV-116) or hydralazine upregulated nNOS mRNA expression in both SHR and WKY. Marked augmentation of nNOS mRNA expression in the decapsular portion of the adrenal gland by reserpine treatment suggested an intimate relation between nNOS in the decapsular portion of the adrenal gland and the sympathoadrenal system. Reserpine treatment also increased the expression of nNOS protein; however, reserpine treatment did not affect the distribution pattern of nNOS-positive cells (NADPH-diaphorase-positive cells) in the adrenal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1995

Acidic fibroblast growth factor protects memory and immunoreactivity impairment in senescence accelerated mice.

Subcutaneous injection of aFGF once per a week into senescence accelerated mice (SAM)P8 was begun at 3 weeks after birth and continued for 10 months. Saline was injected as a control. Learning and memory and cellular immunological functions in the aFGF (F) group were enhanced significantly and while those of the saline (S) group deteriorated. The number of cholinergic neurons was decreased slightly and choline acetyltransferase activity in individual neurons in the medial septum which send monosynaptic terminals to the hippocampus was significantly decreased in the S group, but were more spared in the F group. The MAO-B activity was significantly lower in the F group than in the S group. The respective densities of muscarinic and NMDA receptors and the aFGF receptor, i.e. FGFR-1 in the hippocampus were also significantly higher in the F group than in the S group. The delayed type hypersensitivity reactions (DTH) in the footpad caused by challenge with trinitrophenyl or sheep red blood cells as measured at the end of the 2nd and 7th months, indicated the T cell immune response. Both types of DTHs were reduced in the 7th month as compared with the 2nd month in the S group. However, aFGF administration protected against this reduction in response with age. These results show that aFGF provides protection against impairment of not only learning and memory but also the DTH immunoreactivity in SAMP8, indicating thereby a close relationship between learning-memory and T cell immune function.

Aging↗
PubMed1994

Acidic fibroblast growth factor-like immunoreactivity in rat brain following cerebral infarction.

Expression of acidic fibroblast growth factor (aFGF) was studied by immunocytochemistry in the rat brain with or without cerebral infarction. In a model of infarction produced by occlusion of the middle cerebral artery, aFGF-positive staining that was not seen in controls appeared in both neurons and macrophages. Positive neurons were distributed mainly in the periventricular region of the hypothalamus. The neuronal aFGF began to be detectable about 24 h after the occlusion. The staining intensity for such neuronal aFGF increased until about 14 days after the surgery, but decreased gradually and was undetectable after more than 30 days. Positive macrophages first appeared on the 3rd day after the occlusion and were persistently seen up to the 7th day, but were no longer visible after 14 days. The present results suggest that aFGF may be involved in the repair processes following brain infarction.

Animals↗
PubMed1994

Postnatal development of [D-Ala2]deltorphin-I-like immunoreactive structures in the rat brain.

[D-Ala2]deltorphin-I, a highly selective ligand for delta opioid receptors, is a heptapeptide originally purified from frog skin. Previous immunohistochemical studies indicate that [D-Ala2]deltorphin-I-like molecule(s) may be present in adult rat brain, including specific neuronal cells and fibers partially overlapping with the mesocortical and nigrostriatal dopaminergic systems. Here, we examined the developmental aspect of such immunoreactive brain structures in early postnatal rats. In newborn to 21-day-old rats, positive staining in the brain occurred mainly in subpopulations of neurons and occasionally in tanycytes. On postnatal day 0, neuronal cell bodies containing [D-Ala2]deltorphin-I-like immunoreactivity were found in various brain regions, including the olfactory tubercle, ventral pallidum, hippocampus, ventral tegmental area, pars compacta of the substantia nigra, supramammillary nucleus, and dorsal raphe nucleus. Immunoreactive nerve fibers were observed in the main and accessory olfactory bulbs, olfactory tubercle, prelimbic area, anterior cingulate cortex, neostriatum, accumbens, lateral septal nucleus, lateral habenular nucleus, and superior colliculus. As pups grew, positive staining of cell bodies decreased gradually in both density and intensity, and those in the olfactory tubercle and ventral pallidum were no longer visible on postnatal day 14. On postnatal day 21, positive cells were found only in the ventral midbrain, including the pars compacta of the substantia nigra, ventral tegmental area, A8 region, and supramammillary nucleus. Positive fibers also decreased in density with age except in the accessory olfactory bulb, olfactory tubercle, prelimbic area, and anterior cingulate cortex.

Amino Acid Sequence↗
PubMed1994

Retention of basic fibroblast growth factor immunoreactivity in dopaminergic neurons of the substantia nigra during normal aging in humans contrasts with loss in Parkinson's disease.

A count of pigmented neurons per mm3 in sections of the substantia nigra at the level where the oculomotor nerve emerges in 11 neurologically normal controls aged 15-82 showed the expected slow loss of such neurons with age. Most (82 +/- 3.8%) of the pigmented neurons showed immunoreactivity for basic fibroblast growth factor (bFGF) and this percentage was unaffected by age. This is in marked contrast to the case in Parkinson's disease where only some 12.7 +/- 2.6% of the remaining dopaminergic neurons showed bFGF-like immunoreactivity, providing further evidence against the hypothesis that Parkinson's disease is due to some early insult followed by age-related attrition of the remaining neurons.

Adolescent↗
PubMed1994

Effects of neopterin on ischemic neuronal damage in gerbils.

The effects of neopterin on ischemic neuronal damage were examined. Cerebral ischemia was produced in the gerbil by bilateral common carotid occlusion for 8 min or unilateral occlusion for 30 min, which resulted in delayed neuronal death in the CA1 region of the hippocampus. However, preischemic treatment with neopterin (3 mg/kg i.p.) markedly reduced hippocampal neuronal damages in both cases. Since neopterin serves both as an antioxidant and as an oxidant depending on its redox state, these findings indicate that neopterin attenuates the ischemic neuronal injury by scavenging oxygen free radicals and/or by inhibiting their generation.

Animals↗
PubMed1994

Delayed expression of c-fos protein in rat hippocampus and cerebral cortex following transient in vivo exposure to hypoxia.

The time course of c-fos protein expression after hypoxia was examined in rat hippocampus and cerebral cortex using an immunohistochemical method. The rats were exposed to in vivo hypoxia for 30 min in a chamber containing 5% O2 and 95% N2. Immediately after the treatment, c-fos protein-like immunoreactivity was observed in the granule cell layer of the dentate gyrus. The change was transient, and the density of immunoreactive cells returned quickly to a control level 3 h after the exposure. However, the density of positive cells was again increased 1 day after hypoxia and reached the maximum 7 days after. In the cerebral cortex, on the other hand, no change was detected in the pattern of staining at any time, with an exception on 21 days after hypoxia. At this period, positively stained neurons were significantly increased in both density and intensity throughout the entire extent of the cerebral cortex including the cingulate gyrus. These results clearly indicate that hypoxia induces different patterns of c-fos protein expression among various regions of the brain. The biphasic pattern seen in the dentate gyrus as well as the delayed expression in the cerebral cortex may be related to delayed neuronal damages induced by hypoxia.

Animals↗
PubMed1994

Early response of brain resident microglia to kainic acid-induced hippocampal lesions.

We investigated the early response of microglia with complement and other proteins in well controlled rat central nervous system lesions. A selective neuronal degeneration in the hippocampal CA3 region was induced without direct tissue damage by an intraventricular injection of a small amount of kainic acid. As early as 1 h post injection, complement proteins C1q, C4, and C3 and immunoglobulin(Ig)G were found in the lesioned area. After 2 h, non-specific leakage of other plasma proteins occurred. By 3 h, reactive microglia gathered around the injured pyramidal neurons. Areas surrounding the lesions were depleted, on the other hand, indicating that these reactive microglia had originally resided in and migrated from such vacant areas. Upregulation of ICAM-1 expression by vascular endothelial cells commenced after 6 h. LFA-1-positive leucocytes were, then, accumulated in the vasculature, which was followed by an infiltration of leucocytes into the lesioned brain parenchyma. These results indicate that, following an acute neuronal injury, the response of the humoral factors such as complement proteins and IgG precedes the microglial reaction. Activation of vascular endothelial cells and subsequent infiltration of blood leucocytes occurs much later than the activation and migration of brain resident microglia. The origin of complement proteins and IgG in the lesioned brain parenchyma remains to be determined, although the production of complement proteins by microglia is suggested.

Animals↗
PubMed1994

Phylogenetic and ontogenetic study of neuropeptide Y-containing nerves in the liver.

The distribution of neuropeptide Y was investigated by light and electron microscopic immunohistochemistry in the liver of various vertebrates including the eel, carp, bullfrog, turtle, chicken, mouse, rat, guinea-pig, dog, monkey and human. The ontogenetic development of neuropeptide Y was also studied in the mouse liver. In all species examined except the eel, neuropeptide Y-like immunoreactivity was detected in nerve fibres. In the carp, bullfrog, turtle, chicken, mouse and rat, positive fibres were distributed around the wall of hepatic vessels and the bile duct of the Glisson's sheath. The density of the positive fibres increased with evolution. On the other hand, in the guinea-pig, dog monkey and human, numerous neuropeptide Y-positive fibres were observed not only in the Glisson's sheath but also in the liver parenchyma. Positive fibres formed a dense network to surround hepatocytes. The present immunoelectron microscopic study has confirmed that neuropeptide Y-positive terminals are closely apposing to hepatocytes. Ontogenetically, neuropeptide Y-positive fibres were first found in embryonic liver of 19-day-old mice. Positive fibres increased with age and the highest peak was seen one week after birth. This ontogenetic pattern has suggested that neuropeptide Y plays a certain role in developing liver.

Animals↗
PubMed1994

Loss of insulin receptor immunoreactivity from the substantia nigra pars compacta neurons in Parkinson's disease.

Immunohistochemistry using both a newly developed polyclonal, and a commercially available monoclonal, anti-insulin receptor antibody was done on the midbrain from cases of idiopathic Parkinson's disease (PD), Alzheimer's disease, amyotrophic lateral sclerosis, vascular parkinsonism and non-neurological controls. Both antibodies gave identical patterns of neuronal staining. The neurons of the oculomotor nucleus were immunopositive in all the brains. However, the neurons in the pars compacta of the substantia nigra, paranigral nucleus, parabrachial pigmental nucleus, tegmental pedunculopontine nucleus, supratrocheal nucleus, cuneiform nucleus, subcuneiform nucleus and lemniscus medialis, which were positive in other diseases and in non-neurological controls, were not stained by these antibodies in PD brains. These results suggest that, in PD, a dysfunction of the insulin/insulin receptor system may precede death of the dopaminergic neurons.

Adult↗
PubMed1994

Effects of fibroblast growth factors and related peptides on food intake by rats.

The effects of acidic fibroblast growth factor (aFGF), basic FGF (bFGF), and related peptides, such as aFGF fragments, on food and water intake were investigated. Infusion of aFGF and bFGF into the third cerebral ventricle significantly suppressed food intake. The potency of aFGF was 1.5 that of bFGF in food intake inhibition. Both FGFs also suppressed water intake. Infusion of a carboxyl-terminal fragment of aFGF, aFGF-(114-140), did not affect food intake, whereas an amino-terminal fragment of aFGF, aFGF-(1-15), was significantly inhibitory. Other amino-terminal fragments, aFGF-(1-20) and aFGF-(1-29), did not affect food intake. However, [Ala16]aFGF-(1-29), in which the cysteine residue at position 16 was replaced with alanine, significantly suppressed food intake. Infusions of functional antagonists for FGFs, anti-aFGF, anti-bFGF, and anti-aFGF-(1-15) IgGs, into the lateral hypothalamus significantly increased food intake. The results suggest that: aFGF, bFGF, and some amino-terminal peptides of aFGF participate in the central regulation of food intake; the lateral hypothalamus is involved in their feeding suppression actions; and these peptides may function as physiologically relevant substances in the adult central nervous system, other than as neurotrophic factors.

Animals↗
PubMed1994

Immunohistochemical demonstration of [D-Ala2]deltorphin-I in amacrine cells of rat retina.

In an immunohistochemical study, a specific antiserum raised against [D-Ala2]deltorphin-I (DADTI), a highly selective ligand for delta opioid receptors, was used to demonstrate immunoreactive structures in the rat retina. [D-Ala2]Deltorphin-I immunoreactivity occurred in a subpopulation of the retinal amacrine cells situated in the inner nuclear layer. Their stained processes were mainly distributed in the sublaminae 1 and 3 of the inner plexiform layer. A few positive cells, probably displaced amacrine cells, were also seen in the ganglion cell layer. Double immunostaining revealed that 12.8% of DADTI-immunoreactive cells costored GABA and 27.7% costored neuropeptide Y, whereas only few DADTI-positive cells colocalized tyrosine hydroxylase (0.3%) and almost no other peptides. These findings suggest that some retinal amacrine cells possess DADTI-like molecule(s), possibly acting as neurotransmitter(s) or neuromodulator(s).

Amino Acid Sequence↗
PubMed1994

Immunohistochemical localization in the rat brain of an epitope corresponding to the fibroblast growth factor receptor-1.

The localization of fibroblast growth factor receptor-1 was investigated in rat brain by immunohistochemistry using a polyclonal antibody against an acidic peptide sequence of chicken fibroblast growth factor receptor-1. For raising the antisera in rabbits, we synthesized the oligopeptide EDDDDEDDSSSEEKEAD which is a highly acidic region of chicken fibroblast growth factor receptor-1. The oligopeptide was used as a haptenic antigen by conjugating with poly-L-glutamate as a carrier protein. On immunospot assay, the best antiserum was capable of detecting 15.7 pmols of both the chicken and its analogous human oligopeptides but failed to react even with up to 1 nmol of poly-L-glutamate. When rat brain homogenate was examined by Western blots, the antiserum revealed two bands with molecular weights of 145,000 and 75,000 corresponding to known sizes of the membrane-bound and secreted forms of the rat receptor, respectively. Immunohistochemistry in rat brain demonstrated that putative fibroblast growth factor receptor-1 immunoreactivity sites were present mainly in neurons but also in tanycytes and ependymal cells. Positive neurons were distributed widely in various brain regions, but were particularly abundant in such regions as the lateral hypothalamus, substantia nigra, locus coeruleus and raphe nuclei. The present study suggests that fibroblast growth factor receptor-1 is expressed preferentially in certain neuronal systems that appear to be under the influence of fibroblast growth factors in the normal brain. The result should facilitate study of the functional significance of fibroblast growth factors in these brain neurons.

Amino Acid Sequence↗
PubMed1994

Lignocaine-induced convulsion does not induce c-fos protein (c-Fos) in rat hippocampus.

Recent studies have shown that proto-oncogene c-fos mRNA is induced in the central nervous system by a variety of stimuli including generalised convulsions. In this study, the expression of c-fos protein (c-Fos) following lignocaine-induced convulsions was examined and compared with that following convulsions induced by non-anesthetic convulsants, such as pentylenetetrazol, kainic acid and electroconvulsive shocks, in rat brain. Administration of 120 mg.kg-1 lignocaine by the intraperitoneal route induced generalised convulsions in all rats examined within 10 min. C-Fos was markedly induced in the piriform cortex and amygdala, and slightly induced in the neocortex and thalamus, while no c-Fos expression was observed in the hippocampus. In contrast, c-Fos expression following generalised convulsions induced by non-anaesthetic convulsants was very marked in the hippocampal region, piriform cortex and amygdala, and extended to the thalamus and neocortex. These results contradict those of previously reported local cerebral metabolic studies using 2-deoxyglucose as a metabolic marker, and suggest that lignocaine-induced convulsions, unlike those induced by non-anaesthetic convulsants, may not cause severe sequelae (plastic changes) in the hippocampus.

Animals↗
PubMed1994

Acidic FGF expression in the surroundings of senile plaques.

Immunohistochemical examination of postmortem brain tissue of Alzheimer's disease revealed that acidic fibroblast growth factor (aFGF) was specifically expressed in a subpopulation of reactive astrocytes which were congregated at the margin of the senile plaque. Double immunostaining indicated that such upregulation of aFGF expression might be related to the presence of reactive microglia rather than beta-amyloid protein deposits. Although, on the other hand, immunohistochemical staining for fibroblast growth factor receptor-1 occurred in some cortical neurons of Alzheimer's disease, the staining pattern did not differ from that in age-matched controls. Possible significance of aFGF-positive astrocytes in the surroundings of the senile plaque will be discussed in relation to receptor mediated or non-mediated mechanisms.

Aged↗