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Biomedical subjects

A Nitta

Publications and source records attributed to A Nitta.

At least 37 records · Page 2Linked to original sources
PubMed1999

Induction of a physiologically active brain-derived neurotrophic factor in the infant rat brain by peripheral administration of 4-methylcatechol.

Effects of 4-methylcatechol (4MC), a known potent stimulator of nerve growth factor (NGF) synthesis, on expression of brain-derived neurotrophic factor (BDNF) mRNA and BDNF-like immunoreactivity (BDNF-LI) was investigated in infant rat brains. A single intraperitoneal administration of 4MC caused transient increases in the levels of BDNF mRNA and BDNF-LI in neurons of the cerebral cortex from 1 to 3 h and 3 to 12 h, respectively, after the injection. Repetitive injections of 4MC to newborn rats (12-h intervals for 10 days) caused a marked and dose-dependent elevation of the level of BDNF mRNA in the whole brain besides elevating the number of cells containing calbindin D-28 and enhancing its immunoreactive intensity in the pyriform cortex and hippocampus. These findings demonstrate that 4MC stimulates de novo synthesis of BDNF in the infant rat brain, resulting in acceleration of the developmental expression of calbindin D-28.

Age Factors↗
PubMed1999

Impairments of long-term potentiation in hippocampal slices of beta-amyloid-infused rats.

In this study, we investigated the neuronal activity of hippocampal slices from the beta-amyloid protein-infused (300 pmol/day for 10-11 days) rats using the extracellular recording technique. Perfusion of nicotine (50 microM) reduced the amplitude of electrically evoked population spikes in the CA1 pyramidal cells of the vehicle control rats, but not in those of the beta-amyloid protein-infused rats, suggesting the impairment of nicotinic signaling in the beta-amyloid protein-infused rats. Long-term potentiation induced by tetanic stimulations in CA1 pyramidal cells, which was readily observed in the vehicle control rats, was also impaired in the beta-amyloid protein-infused rats. Nicotinic blockade by adding hexamethonium into the perfused solution inhibited long-term potentiation induction. Taken together, our previous and present results suggest that beta-amyloid protein infusion impairs the signal transduction mechanisms via nicotinic acetylcholine receptors. This dysfunction may be responsible, at least in part, for the impairment of long-term potentiation induction and may lead to learning deficits.

Amyloid beta-Peptides↗
PubMed1999

Brain-derived neurotrophic factor prevents neuronal cell death induced by corticosterone.

Corticosterone (CORT), one of the glucocorticoids, causes neuronal damage in the hippocampus, but the mechanism(s) of action underlying its effects remains unknown. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that belongs to the neurotrophin family, affects the survival and/or differentiation of various types of neurons in vitro, and is able to antagonize neuronal death induced by various brain insults or neurotoxins in vivo. In this study, the effects of CORT on BDNF protein contents and mRNA expression were investigated in relation to neuronal survival/death of cultured rat hippocampal neurons, because the colocalization of BDNF with its receptor, TrkB, suggests that BDNF may exert its putative protective and trophic effects through an autocrine mechanism in the hippocampus. Administration of CORT accelerated the neuronal death that proceeds after serum deprivation, and simultaneously reduced the levels of BDNF mRNA and intracellular BDNF content. Exogenously added BDNF actually attenuated CORT-induced neuronal death, but not in the presence of K252a, an inhibitor of the tyrosine kinase activity of Trk family receptors. These observations suggest that CORT induces damage to hippocampal neurons, at least partly, via reducing their BDNF synthesis.

Animals↗
PubMed1999

Microsphere embolism-induced elevation of nerve growth factor level and appearance of nerve growth factor immunoreactivity in activated T-lymphocytes in the rat brain.

Changes in nerve growth factor (NGF) level and type of cells producing NGF were investigated in the rat brain after sustained cerebral embolism. The NGF level was determined by a two-site enzyme immunoassay specific for NGF. The cerebral cortex, striatum, and hippocampus of the embolized hemisphere maximally contained 2.4-, 2.4-, and 1.7-times higher NGF levels than the corresponding regions of the nonembolized hemisphere. A significant increase was transiently observed for 1 week in the cerebral cortex and striatum, whereas the increase was longer lasting, at least of 4 weeks' duration, in the hippocampus. To examine the localization of NGF-like immunoreactivity (NGF-LI), we used a newly developed anti-NGF peptide antiserum that specifically recognized a 30-kDa molecule(s) in the hippocampal extracts or in NGF cDNA-transfected cells, suggesting that the antibody predominantly reacted with the putative NGF precursor protein(s). NGF-LI, which was localized in neurons of the normal or non-embolized hemisphere, was reduced, and on the embolized side new signals emerged in small non-neuronal cells having a round shape. These included cells with common leukocyte antigen CD45 and T-lymphocyte antigen CD3, which did not appear in the normal or non-embolized hemisphere. NGF-LI and CD3 were colocalized in a substantial number of the cells, suggesting that some activated T-lymphocytes produce NGF for neuronal regeneration after sustained cerebral embolism.

Animals↗
PubMed1999

Generalized peritonitis with pneumoperitoneum caused by the spontaneous perforation of pyometra without malignancy: report of a case.

Spontaneous perforation is a very rare complication of pyometra. We report herein the case of an 88-year-old woman who presented with muscular rigidity and free air on abdominal X-ray films. Perforation of the gastrointestinal tract was diagnosed preoperatively, and an emergency laparotomy was performed. A total hysterectomy with bilateral salpingo-oophorectomy was carried out under the diagnosis of generalized peritonitis caused by the spontaneous perforation of pyometra. The culture of purulent fluid from the abdominal cavity showed only Escherichia coli, with no anaerobic bacteria. Histological examination revealed pyometra with necrosis of the endometrium and no evidence of malignancy. The patient was discharged on postoperative day 68 without any major complications. Pyometra is an unusual cause of peritonitis, but it must be considered as a possible diagnosis in elderly women presenting with an acute abdomen. Following this case report, we discuss the problems associated with establishing a correct preoperative diagnosis of generalized peritonitis caused by the spontaneous perforation of pyometra.

Aged↗
PubMed1999

Endogenous neurotrophin-3 is retrogradely transported in the rat sciatic nerve.

To address the active transport of neurotrophins, nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 in the peripheral nerves, we examined the levels of proteins and messenger RNAs in the sciatic nerve of adult rats following transection, using enzyme immunoassays and reverse transcription polymerase chain reaction method, respectively. Neurotrophin-3 protein increased one day after transection only in the distal segment next to the transection site and returned to the original level two days later. This was considered to reflect accumulation of neurotrophin-3 transported from the periphery toward the neuronal cell bodies, because the neurotrophin-3 messenger RNA level was not changed in any sciatic segments during this experimental period. An increase in brain-derived neurotrophic factor protein was observed simultaneously in both the distal and proximal stumps three days after transection. Brain-derived neurotrophic factor messenger RNA was elevated in the same stumps two days after transection, suggesting that brain-derived neurotrophic factor was produced within the transected stumps. These observations demonstrate that neurotrophin-3, like nerve growth factor, is retrogradely transported in the sciatic nerve but that brain-derived neurotrophic factor is not. This suggests that neurotrophin-3 plays a role in the conveyance of trophic signals from target organs to neurons.

Animals↗
PubMed1999

[Neonatal transient hypothyroidism].

Neonatal screening for congenital hypothyroidism can detect permanent and transient hypothyroidism. The latter condition is called neonatal transient hypothyroidism. This may result from various causes, but, especially, it should be suspected whenever there is a history of maternal autoimmune thyroid disease, including Hashimoto thyroiditis, Graves disease, hypothyroidism on replacement therapy, or recurrent congenital hypothyroidism of a transient nature in subsequent siblings. Transplacental TSH-receptor antibodies may affect fetal or neonatal thyroid function. Although thyroid dysfunction may be transitory, long-term follow-up is desirable.

Congenital Hypothyroidism↗
PubMed1999

4-methylcatechol increases brain-derived neurotrophic factor content and mRNA expression in cultured brain cells and in rat brain in vivo.

Practical use of brain-derived neurotrophic factor (BDNF) as therapy is limited by two serious problems, i.e., its inability to cross the blood-brain barrier and its instability in the bloodstream. In the present study, we investigated the effects of 4-methylcatechol (4-MC), which stimulates nerve growth factor synthesis and protects against peripheral neuropathies in rats, on BDNF content and mRNA expression in cultured brain cells and in vivo in the rat brain. 4-MC elevated BDNF content in culture media of both rat astrocytes and neurons with different dose-response relations. The increase in BDNF mRNA level was correlated with the increase in BDNF content, demonstrating that 4-MC can stimulate BDNF synthesis of both neurons and astrocytes. Then we examined the in vivo effects of 4-MC. First, we found that ventricularly administered 4-MC facilitated an increase in the BDNF content in the cerebral cortex and hippocampus in association with its diffusion into the brain parenchyma. Second, i.p. administration of 4-MC enhanced BDNF mRNA expression in the infant rat brain, in which the blood-brain has not yet fully been established. These results demonstrate that 4-MC, once delivered into the brain, can stimulate BDNF synthesis.

Animals↗
PubMed1998

Brain-derived neurotrophic factor-like immunoreactivity in the adult rat central nervous system predominantly distributed in neurons with substantial amounts of brain-derived neurotrophic factor messenger RNA or responsiveness to brain-derived neurotrophic factor.

Distribution of brain-derived neurotrophic factor-like immunoreactivity was investigated in the adult rat brain using two types of antibodies against peptides, V2 and V4, unique to the brain-derived neurotrophic factor. Western blot analysis showed that both antibodies specifically bound brain-derived neurotrophic factor, but not other neurotrophins, and that they recognized identical molecules of 18,000 mol. wt, but not the 14,500 mol. wt mass of mature form, in extracts from the rat hippocampus. Both antibodies recognized an identical precursor form (30,000 mol. wt) in lysates of COS7 cells transfected with brain-derived neurotrophic factor gene. These indicated that both antibodies predominantly recognized identical precursor protein(s) or its derivative(s) probably because of their much higher amounts than the amount of mature protein. Immunochemical studies showed that anti-V2 predominantly stained the cytoplasm of cells; whereas the anti-V4 bound to the nucleus, suggesting that the tertiary structure of immunoreactive molecules changed depending on their location. Cell populations with the immunoreactivity were similar in most brain sections stained with either anti-V2 or anti-V4 antibodies. These results suggest that brain-derived neurotrophic factor-like immunoreactivity distributes, in most cases, in neurons responding to brain-derived neurotrophic factor and in neurons expressing abundant brain-derived neurotrophic factor messenger RNA. These, taken together with other results concerning distributions of messenger RNAs of brain-derived neurotrophic factor and TrkB, provide additional information to elucidate the function of brain-derived neurotrophic factor in the rat central nervous system.

Animals↗
PubMed1998

Simultaneous expression of brain-derived neurotrophic factor and neurotrophin-3 in Cajal-Retzius, subplate and ventricular progenitor cells during early development stages of the rat cerebral cortex.

To identify production sites and action targets of neurotrophins during neurogenesis, we investigated immunoreactivities of neurotrophins and their tyrosine kinase receptors in the cerebral cortex of rat embryos. Two sets of ligand-receptor systems, brain-derived neurotrophic factor/TrkB and neurotrophin-3/TrkC, were expressed simultaneously in Cajal-Retzius, subplate neurons and ventricular multipotent stem cells at embryonic days 13 and 15. Intraventricular administration of brain-derived neurotrophic factor or neurotrophin-3 at embryonic day 16 markedly modulated microtubule-associated protein II and/or Hu protein expression in different ways in the cortical plate cells by embryonic day 20. These observations indicate the involvement of autocrine and/or local paracrine action of brain-derived neurotrophic factor and/or neurotrophin-3 during formation of the cerebral cortex.

Aging↗
PubMed1998

Memory facilitation and stimulation of endogenous nerve growth factor synthesis by the acetylcholine releaser PG-9.

The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.

Acetylcholine↗
PubMed1997

BDNF and NT-3 modulate expression and threonine phosphorylation of microtubule-associated protein 2 analogues, and alter their distribution in the developing rat cerebral cortex.

Effects of brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3 on the expression of structural or synapse-associated proteins were examined in the developing rat cerebral cortex. Following ventricular administration of BDNF or NT-3 at embryonic day (E) 16, expression of microtubule-associated protein (MAP) 2 of 280 kDa was enhanced at E18 and/or E20, and threonine phosphorylation of MAP2 analogues of 120 and 66 kDa was modulated in different ways. NT-3 basically altered the distribution of MAP2 proteins at E20. These findings suggest that NT-3 and BDNF play a role in regulating production and phosphorylation of MAP2 analogues during development of the rat cerebral cortex.

Animals↗
PubMed1997

Administration of corticosterone alters intracellular localization of brain-derived neurotrophic factor-like immunoreactivity in the rat brain.

We investigated the distribution of immunoreactivity for brain-derived neurotrophic factor (BDNF) in rat brain after peripheral administration of corticosterone or vehicle. In the immunohistochemical study, BDNF-like immunoreactivity (LI) was observed predominantly in the nucleus of the cortical and hippocampal neurons in the brain of vehicle-treated rats. In corticosterone-treated rats, BDNF-LI was markedly reduced in the nucleus and concomitantly increased in cytoplasm. Western immunoblot study also demonstrated that corticosterone significantly reduced BDNF-LI in the nuclear fraction of the cerebral cortex and hippocampus. These results indicate that corticostrone regulates the intracellular localization of BDNF and/or its derivatives in the rat brain.

Animals↗
PubMed1997

Effects of metrifonate on memory impairment and cholinergic dysfunction in rats.

Metrifonate is an organophosphorous compound that has been used in the treatment of schistosomiasis. In this study, we investigated the effects of metrifonate on the impairment of learning and on central cholinergic dysfunction in scopolamine-treated and basal forebrain-lesioned rats. Oral administration of metrifonate (5.0-15.0 mg/kg) ameliorated the scopolamine- and basal forebrain. lesion-induced learning impairment in the water maze and passive avoidance tasks. Metrifonate (50 and 100 mg/kg) also significantly increased extracellular acetylcholine levels but decreased choline levels in the cerebral cortex of the basal forebrain-lesioned rats. The basal forebrain lesion decreased the cholinesterase activity in the cerebral cortex, and metrifonate (100 mg/kg) further reduced the cholinesterase activity. However, cholinesterase inhibition was not observed at the dose that ameliorated learning impairments. These results indicated that metrifonate ameliorated the impairment of learning in both scopolamine-treated and basal forebrain-lesioned rats by not only increasing extracellular acetylcholine levels by inhibiting cholinesterase, but also by undefined other mechanism(s). This finding suggests the usefulness of metrifonate for the therapy of Alzheimer's disease.

Acetylcholine↗
PubMed1997

Establishment of a cisplatin-resistant gastric carcinoma cell line OCUM-2M/DDP.

A cis-diamminedichloroplatinum (CDDP)-resistant scirrhous gastric cancer cell line, OCUM-2M/DDP, was established by chronic exposure of cells of the parent scirrhous gastric cancer cell line, OCUM-2M, to CDDP at progressively increasing concentrations. The OCUM-2M/DDP cell line had an 11.3-fold higher level of resistance relative to its parent cell line as determined by a succinate dehydrogenase inhibition test. The biological and biochemical characteristics of the resistant and parent cell line were compared. There were differences in the modal chromosome number and DNA index, suggesting that some alterations of the DNA in the CDDP-resistant cells had occurred. Neither the parent nor resistant cell line expressed mdr-1 mRNA. After exposure to CDDP for 4 h, the intracellular platinum content of OCUM-2M cells was significantly higher than that of OCUM-2M/DDP cells (51.9 +/- 1.8 vs 16.4 plus 1.0 ng/mg protein, mean +/- SD, respectively). The GSH levels in OCUM-2M cells and OCUM-2M/DDP cells were 3.5 +/- 1.0 micrograms/mg protein and 16.8 +/- 1.2 micrograms/mg protein, respectively. These levels were also significantly different. These findings suggest that the possible mechanisms of acquired resistance to CDDP in OCUM-2M/DDP cells may be a decrease in intracellular CDDP accumulation and detoxication by GSH. This OCUM-2M/DDP cell line could be used in further investigations of the mechanism of CDDP resistance in gastric cancer.

Antineoplastic Agents↗
PubMed1997

Orally active NGF synthesis stimulators: potential therapeutic agents in Alzheimer's disease.

The degeneration of cholinergic neurons may be responsible for cognitive impairment in patients with Alzheimer's disease (AD). Since nerve growth factor (NGF) plays an important role in the survival and maintenance of cholinergic neurons in the central nervous system, this factor may have some beneficial effects on the cognitive impairment observed in patients with AD. However, since NGF does not cross the blood-brain barrier and is easily metabolized when administered peripherally, it can only be used when directly injected into the brain. In this review, we show that repeated oral administration of the NGF synthesis stimulators, idebenone and propentofylline, partially restored the age-associated decrease of NGF in the frontal and parietal cortices. Furthermore, this treatment attenuated the impairment of performance in the water maze, passive avoidance, and habituation tasks in rats with bilateral forebrain lesions, and in rats which had received continuous infusion of anti-NGF antibody into the septum. The behavioral improvement induced by idebenone and propentofylline was accompanied by recovery of both the reduced activity of choline acetyltransferase and the changes in [3H]QNB binding. These results suggest that the use of NGF synthesis stimulators may provide a novel therapeutic approach to cholinergic dysfunction.

Alzheimer Disease↗
PubMed1997

Effects of metrifonate on impairment of learning and dysfunction of cholinergic neuronal system in basal forebrain-lesioned rats.

Several studies have indicated the possibility of using cholinesterase (ChE) inhibitors as therapeutic drugs for Alzheimer's disease. Metrifonate (MTF) is an organophosphorus compound that has been used in the treatment of schistosomiasis. In this study, we investigated the effects of MTF on the impairment of learning and memory, decreased ChE activity and extracellular acetylcholine (ACh) levels in basal forebrain (BF)-lesioned rats. The oral administration of MTF improved the BF-lesion-induced impairment of performance on passive avoidance task. Further, MTF reduced ChE activity in the cerebral cortex. In vivo brain microdialysis studies showed that MTF significantly increased the release of ACh, but decreased that of choline (Ch) in the cerebral cortex of BF-lesioned rats. These results indicated that MTF ameliorates the impairment of performance on passive avoidance task in BF-lesioned rats by increasing the extracellular ACh levels by inhibiting ChE. This suggested that MTF may be useful as a therapeutic drug for Alzheimer's disease.

Acetylcholine↗