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N Karasawa

Publications and source records attributed to N Karasawa.

At least 19 recordsLinked to original sources
PubMed2002

Differential subcellular location of mitochondria in rat serotonergic neurons depends on the presence and the absence of monoamine oxidase type B.

Monoamine oxidase type A and type B are major neurotransmitter-degrading enzymes in the CNS. The type A is present on mitochondrial outer membranes in the whole extent of noradrenergic and dopaminergic neurons, including their axon terminals. The type B is present in serotonergic neurons, but its subcellular localization has not been elucidated. In the present study, we used both a double-labeling immunofluorescence method and electron microscopic immunohistochemistry to examine the subcellular localization of monoamine oxidase type B in serotonergic neurons projecting from the dorsal raphe nucleus to the suprachiasmatic nucleus in the rat brain. In the dorsal raphe nucleus, serotonin-positive neuronal cell bodies were clustered, and virtually all of these cell bodies were also positive for monoamine oxidase type B. By contrast, serotonin-negative neuronal cell bodies were mostly free of this enzyme. Within the neuronal cell bodies and dendrites that were positive for monoamine oxidase type B, most mitochondria contained this enzyme on their outer membranes, but a substantial proportion of mitochondria lacked this enzyme. In the suprachiasmatic nucleus, serotonin-positive varicosities were concentrated, but none of these varicosities exhibited monoamine oxidase type B. In this nucleus, mitochondria were found in almost all serotonin-positive axon terminals, but monoamine oxidase type B was not observed in any axon terminal that contained mitochondria. Our results show that there are two kinds of mitochondria in serotonergic neuronal cell bodies and dendrites: one containing monoamine oxidase type B on their outer membranes, and the other lacking this enzyme. In addition, mitochondria in serotonergic axon terminals do not possess monoamine oxidase type B. It is suggested in serotonergic neurons that only mitochondria lacking monoamine oxidase type B are transported by axonal flow up to axon terminals. It is also probable that mitochondria containing monoamine oxidase type B are transported along the axons, but that this enzyme undergoes a change, for example, conformational change, decomposition or removal from the membranes.

Animals↗
PubMed2001

Evidence for involvement of dysfunctional teeth in the senile process in the hippocampus of SAMP8 mice.

In order to evaluate the involvement of dysfunctional teeth in age-related deficits in hippocampal function, we examined the effect of removal of molar teeth (molarless condition) on neuronal degeneration and glial fibrous acidic protein (GFAP) expression in the hippocampus and on learning ability in a water maze test in young, middle-aged, and aged accelerated senescence-prone mice (SAMP8). The molarless condition enhanced an age-dependent decrease in both learning ability and the number of neurons in the hippocampal CA1 subfield and the age-dependent increase in the number and hypertrophy of GFAP-labeled astrocytes in the same subfield. These observations suggest that the molarless condition may be involved in the senile process in the hippocampus in SAMP8 mice.

Aging, Premature↗
PubMed2000

Impairment of spatial memory and changes in astroglial responsiveness following loss of molar teeth in aged SAMP8 mice.

In order to evaluate the mechanism(s) responsible for senile impairment of cognitive function as a result of reduced mastication, the effects of the loss of the molar teeth (molarless condition) on the hippocampal expression of glial fibrous acidic protein (GFAP) and on spatial memory in young adult and aged SAMP8 mice were studied using immunohistochemical and behavioral techniques. Aged molarless mice showed a significantly reduced learning ability in a water maze test compared with age-matched control mice, while there was no difference between control and molarless young adult mice. Immunohistochemical analysis showed that the molarless condition enhanced the age-dependent increase in the density and hypertrophy of GFAP-labeled astrocytes in the CA1 region of the hippocampus. These effects increased the longer the molarless condition persisted. When the extracellular K+ concentration ([K+]o) was increased from 4 to 40 mM for hippocampal slices in vitro, the mean increase in the membrane potential was about 57 mV for fine, delicate astrocytes, the most frequently observed type of GFAP-positive cell in the young adult mice, and about 44 mV for the hypertrophic astrocytes of aged mice. However, there was no significant difference in resting membrane potential between these cell types. The data suggest that an impairment of spatial memory and changes in astroglial responsiveness occur following the loss of molar teeth in aged SAMP8 mice.

Aging↗
PubMed1999

Two types of aggregate in the cerebral cortex of a seizure-sensitive strain of the Mongolian gerbil.

A 70-kDa protein, P70, found mostly in the pyramidal cells of the cerebral cortex of cobalt-induced epileptogenic rats, has been implicated in epileptogenesis. The presence of a P70-like substance was searched for immunohistochemically in the cerebral cortex of MGS/ldr, a seizure-sensitive strain of the Mongolian gerbil (Meriones unguiculatus) that we previously established. Immunoreactive aggregates were observed in the pyramidal neurons of the motor cortex and the primary somatosensory cortex. Analysis using confocal laser scanning microscopy revealed that the aggregates were often colocalized with a second type of aggregate with red autofluorescence at the marginal zone of the cell somata. Both aggregates appeared and increased before the appearance of generalized tonic-clonic convulsion. These may be involved in some change of physiological function of the cerebral cortex but their presence itself is not enough to determine the occurrence of epileptic seizure because the gerbils that showed no such seizure had both aggregates.

Animals↗
PubMed1999

Reduced mastication stimulates impairment of spatial memory and degeneration of hippocampal neurons in aged SAMP8 mice.

The involvement of reduced mastication in senile dementia was evaluated by examining the effect of cutting off the upper molars (molarless) on spatial memory and numbers of hippocampal neurons in aged SAMP8 mice. Molarless mice showed a decrease in both learning ability in a water maze and neuron density in the hippocampal CA1 region compared with control mice. These changes increased the longer the molarless condition persisted. The data suggest a possible link between reduced mastication and hippocampal neuron loss that may be one risk factor for senile impairment of spatial memory.

Aging↗
PubMed1999

Age-associated changes in the dopamine synthesis as determined by GTP cyclohydrolase I inhibitor in the brain of senescence-accelerated mouse-prone inbred strains (SAMP8).

Our objective in this study was to elucidate the mechanism underlying the decrease in dopamine (DA) levels in the brain with ageing We administered 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I to senescence-accelerated mouse-prones (SAMP8), to inhibit DA and serotonin syntheses, and following immunohistochemical staining, analyzed the immunoreactive intensities (IR-Is) for DA in the nigrostriatal dopaminergic neurons by microphotometry. The DA-IR-Is in the substantia nigra pars compacta and neostriatum of young mice (2 months old) reached a minimal value 3 h after DAHP administration and returned to the control value 12 h after the administration. However, in aged mice (10 months old), the minimal value was reached 6 h after the administration and the value remained at approximately 70 and 80% of the control value at 24 and 72 h, respectively, after DAHP administration. The results suggest that DA turnover is lower in aged mice than in young mice.

Aging↗
PubMed1998

Phenylethanolamine-N-methyltransferase - immunoreactive nerve terminals afferent to the mouse substantia nigra.

In the substantia nigra pars compacta, many phenylethanolamine-N-methyltransferase immunoreactive (PNMT-ir) terminals as well as serotonin-ir terminals were observed for the first time to be very closely situated to the tyrosine hydroxylase (TH)-ir, aromatic L-amino acid decarboxylase-ir, and GTP cyclohydrolase I (GCH)-ir dopaminergic cells [Nagatsu, I., Arai, R., Sakai, M., Yamawaki, Y., Takeuchi, T., Karasawa, N. and Nagatsu, T., Neurosci. Lett., 224 (1997) 185-188]. Immunohistochemical colocalization of TH with GCH or PNMT in the somata and dendrites of TH-positive neurons in the rostral ventrolateral reticular formation of the medulla oblongata (C1 region, [Hokfelt, T., Fuxe, K., Goldstein, M. and Johansson, O., Brain Res., 66 (1974) 235-251]) was proved by a double-labeling immunofluorescence method with a confocal laser-scanning microscope, indicating that the neurons are adrenergic. These results suggest that dopaminergic neurons in the substantia nigra receive PNMT-ir, adrenergic afferents from the C1 region of the medulla oblongata.

Animals↗
PubMed1997

Tyrosine hydroxylase (TH)-only-immunoreactive non-catecholaminergic neurons in the brain of wild mice or the human TH transgenic mice do not contain GTP cyclohydrolase I.

We previously reported the presence of transiently tyrosine hydroxylase (TH)-only-immunoreactive (ir), non-catecholaminergic (non-CAnergic) neurons in some brain regions of postnatal mice; anterior olfactory nucleus, medial geniculate nucleus, and spinal trigeminal nucleus, where CAnergic terminals but not cell bodies are present in the adult wild mouse. These transiently TH-ir brain regions of the postnatal wild mouse showed stable TH-immunoreactivity in the adult brain of the human TH transgenic (hTHTg) mice. TH expression was also observed in the nucleus parabigeminalis of the hTHTg mice. Using the antiserum against GTP cyclohydrolase I (GCH), first rate-limiting enzyme of the biosynthesis of tetrahydrobiopterin (BH4), the cofactor for TH, we proved that these TH-only-ir neurons in the wild mice and in the hTHTg mice were not stained with the antiserum against GCH. The results indicate that these TH-only-ir neurons which do not synthesize the BH4 cofactor do not produce dihydroxyphenylalanine, suggesting a new unknown function of TH in these neurons.

Adult↗
PubMed1997

Immunohistochemical colocalization of GTP cyclohydrolase I in the nigrostriatal system with tyrosine hydroxylase.

Immunohistochemical colocalization of GTP cyclohydrolase I (GCH) in the mouse nigrostriatal system with tyrosine hydroxylase or aromatic L-amino acid decarboxylase in the somata and terminals of GCH-positive catecholaminergic neurons are proved for the first time by a double-labeling immunofluorescence method with a confocal laser-scanning microscope. GCH-immunoreactive somata in the mouse substantia nigra have synaptic contacts with monoaminergic and non-monoaminergic terminals.

Animals↗
PubMed1997

Coexistence of tyrosine hydroxylase and serotonin in the raphe nucleus of the laboratory shrew (Suncus murinus) during postnatal life.

Immunoreactivity (IR) of tyrosine hydoroxylase (TH), which is the rate-limiting enzyme of catecholamine (CA) synthesis, was observed in the serotonergic neurons of the raphe nucleus (RN) of the newborn laboratory shrew from postnatal day (P) 0 to P14. Using an immunohistochemical method involving highly specific antibodies produced in our laboratory, we found that these RN neurons were TH-, GTP cyclohydrolase I-, aromatic L-amino acid decarboxylase-immunoreactive, but DOPA- and dopamine-immunonegative. In addition, they were tryptophan-, 5-hydroxytryptophan- and serotonin-immunoreactive. These results suggest that TH in serotonergic neurons of RN of laboratory shrew has no function as a CA-synthesizing enzyme but may play some role as a regulator or a subsidiary factor in the postnatal development of serotonergic neurons.

Animals↗
PubMed1997

Immunocytochemical study of catecholaminergic neurons in the senescence-accelerated mouse (SAM-P8) brain.

The catecholaminergic neurons of senescence-accelerated mice (SAM-P8) were analyzed by immunohistochemical microphotometry in terms of immunoreactivities to aromatic L-amino acid decarboxylase (AADC), dopamine (DA), or noradrenaline (NA). Accelerated senescence-resistant mice (SAM-R1) were used as control mice. The immunoreactivities to AADC, DA, and NA of the catecholaminergic neurons of the SAM-P8 mice were weaker than those of the SAM-R1 mice in all the brain regions. Immunoelectron microscopy revealed progressive degeneration of dopaminergic neurons and their terminal fibers in the substantia nigra as well as in noradrenergic neurons and their proximal dendrites in the locus coeruleus of the SAM-P8 mice. In contrast, there was no difference between the SAM-P8 and SAM-R1 mice in the distribution of AADC-only positive neurons (designated as D neurons in the rat brain by Jaeger et al.) nor in their immunoreactivities. These results may indicate that DA neurons in the substantia nigra and NA neurons in the locus coeruleus degenarate more rapidly during aging in SAM-P8 mice than in control SAM-R1 mice and that D neurons may function as a part of a compensatory system for the decreases in catecholaminergic neurons during aging.

Aging↗
PubMed1996

Transient appearance of GTP cyclohydrolase I--positive non-monoaminergic neurons in the ventral lateral geniculate nucleus of postnatal mice.

The transient appearance of GTP cyclohydrolase I (GCH)-immunoreactive (ir) cells in the ventral lateral geniculate nuclear region of mice was detected by use of an avidin-biotin peroxidase complex method with an antibody specific for an oligopeptide of rat GCH (residues from 12 to 23, GFPERELPRPGA). In this brain region, we found for the first time novel GCH-ir cells already at postnatal day 1 (P1). The numbers reached maximum at P14 and decreased until P29, and they had mostly disappeared by P56. These cells were tyrosine hydroxylase negative and aromatic L-amino acid decarboxylase negative, indicating a lack of dopamine or serotonin production, and thus do not belong to the monoaminergic neuron system.

Age Factors↗
PubMed1996

Transient appearance of tyrosine hydroxylase-immunoreactive non-catecholaminergic neurons in the medial geniculate nucleus of postnatal mice.

Tyrosine hydroxylase-immunoreactive (TH-ir) cells were found to appear transiently in the medial geniculate nuclear region of mice at postnatal day 7 (P7) by use of an avidin-biotin peroxidase complex (ABC) method for the first time. The numbers of TH-ir cells reached maximum between P14 and P21 and decreased until P29. These cells were GTP cyclohydrolase I-negative, aromatic L-amino acid decarboxylase-negative, and dopamine-negative. Thus, they do not belong to the catecholaminergic neuron system, because they lack dopamine production. The results suggest that TH in the cells in the medial geniculate nuclear region of mice has some new functions besides catecholamine biosynthesis.

Animals↗
PubMed1996

Dopamine produced from L-DOPA is degraded by endogenous monoamine oxidase in neurons of the dorsal raphe nucleus of the rat: an immunohistochemical study.

The aim of the present study is to examine by immunohistochemistry whether dopamine produced from L-DOPA in serotonin neurons of the rat brain is degraded by endogenous monoamine oxidase (MAO). In rats that received intraperitoneally L-DOPA plus a peripheral decarboxylase inhibitor, carbidopa, a cluster of dopamine-immunoreactive neurons was found in the dorsal raphe nucleus (DR). In L-DOPA/carbidopa-injected rats that were pretreated with an intraperitoneal injection of a MAO inhibitor, pargyline, when compared with the L-DOPA/carbidopa-injected rats without the pargyline pretreatment, neurons of the cluster of the DR became much darker in dopamine staining. The distribution of dopamine-stained neurons in the DR of these rats corresponded very closely to the previously reported distribution of serotonin-immunoreactive neurons of normal rats. In normal or only pargyline-injected rats, dopamine-stained neurons were scarcely observed in the DR. We previously showed that serotonin neurons of the rat DR were induced to contain dopamine by the injection of L-DOPA plus carbidopa. These findings suggest that the newly produced dopamine from L-DOPA in serotonin neurons of the rat DR is degraded by endogenous MAO.

Animals↗
PubMed1996

Aromatic L-amino acid decarboxylase is present in serotonergic fibers of the striatum of the rat. A double-labeling immunofluorescence study.

The aim of the present study is to examine whether serotonergic fibers of the striatum of the rat contain aromatic L-amino acid decarboxylase (AADC). By use of a double-labeling immunofluorescence method, we showed that AADC was localized in serotonergic fibers of the striatum and cerebral cortex as well as in serotonergic cell bodies of the midbrain raphe nuclei. We previously demonstrated that serotonergic fibers of the rat striatum contained dopamine after intraperitoneal injection of L-dopa. These findings suggest that dopamine is produced from the injected L-dopa in serotonergic fibers of the rat striatum.

Animals↗
PubMed1996

[The disputes in the Nippon Medical School Foundation and the coming into being of the Tokyo Medical School].

The Nippon Medical School Foundation was an institution that developed after the closing of the Saiseigakusha Medical School, inheriting the spirit of the latter. During the period extending from 1912 to May 1916, the Ministry of education remained reluctant to approve of the Foundation as a Ministry-designated institution. Actively lobbying the Ministry were people such as Tatsukichi Irisawa, a member of the "Meiji Society of Medicine", a partisan clique of the University of Tokyo Medical School. Meanwhile within the Foundation itself, an internal strife took place between the Directors Kenzo Isobe and Taketaro Takizawa, which brought about its disintegration and collapse from within. Some four hundred and fifty students lodged their petition for official approval, sealed with blood, to the School authorities and to the Ministry. Having their petition for approval rejected, all these four hundred and fifty odd students withdrew from the School and founded within the building of the Tokyo Physics School a 'Tokyo Medical Training School'. Some forty students who did not withdraw, in collaboration with members of the teaching staff, re-established the Nippon Medical School Foundation.

Foundations↗