Biomedical subjects

Takeshi Tadano

Publications and source records attributed to Takeshi Tadano.

At least 19 recordsLinked to original sources

PubMed2007

Preventive effect of kami-untan-to on performance in the forced swimming test in thiamine-deficient mice: relationship to functions of catecholaminergic neurons.

The kampo (Japanese herbal) medicine "kami-untan-to" (KUT) has been used for a long time in the treatment of neuropsychiatric disorders. We have recently reported that mice put on a thiamine-deficient (TD) diet exhibit a depressive behavior and impairment in avoidance learning after 20 days, and that this impairment was reversed by the chronic administration of KUT. In the present study, we investigated the effect of KUT on the depressive behavior observed in TD mice by using the forced swimming test. Our results show that oral administration of KUT from the 1st day of TD feeding prevented the increased duration of immobility in TD mice. Administration of KUT from the 10th day of TD feeding also had a beneficial effect on depressive behavior. To examine the relationship between the potential effects of KUT on monoaminergic neuronal functions and the depressive behavior observed in TD mice, we measured the immunohistochemical distribution of tyrosine hydroxylase (TH) in the brain using microphotometry. The fluorescence intensity of TH decreased in the limbic cortex and brainstem in TD mice compared with pair-fed mice as the control group, while KUT treatment protected against these decreases. These results suggest that KUT treatment may prevent a sign of depressive behavior, the animal immobility time, induced by TD feeding through a mechanism that involves the decrease of TH in some brain areas of TD mice.

Analysis of Variance↗

PubMed2006

S-(+)-fenfluramine-induced nociceptive behavior in mice: Involvement of interactions between spinal serotonin and substance P systems.

Intrathecal (i.t.) administration into mice of S-(+)-fenfluramine (0.01-0.1nmol), a serotonin (5-hydroxytryptamine, 5-HT) releaser, produced a behavioral response consisting of scratching, biting and licking. Here, we report the behavioral characteristics and the involvement of interactions between 5-HT and substance P (SP) systems in the S-(+)-fenfluramine-induced behavioral response. The S-(+)-fenfluramine-induced behavioral response peaked at 5-15min and almost disappeared at 20min after injection. The behavior induced by S-(+)-fenfluramine (0.1nmol) was dose-dependently inhibited by an intraperitoneal injection of morphine (0.02-0.5mg/kg), suggesting that the behavioral response is related to nociception. The S-(+)-fenfluramine-induced nociceptive behavior was significantly inhibited by pretreatment with 5-HT antiserum and co-administration of ketanserin, a selective 5-HT2 receptor antagonist. However, WAY-100635, a selective 5-HT1A receptor antagonist, and ramosetron, a selective 5-HT3 receptor antagonist, were not active. On the other hand, SP antiserum and RP67580, a selective neurokinin-1 (NK1) receptor antagonist, significantly inhibited S-(+)-fenfluramine-induced nociceptive behavior. These results suggest that i.t.-administered S-(+)-fenfluramine releases SP through the activation of 5-HT2 receptors subsequent to 5-HT release, and, as a result, produces nociceptive behavior.

Animals↗

PubMed2006

Decreased calcium/calmodulin-dependent protein kinase II and protein kinase C activities mediate impairment of hippocampal long-term potentiation in the olfactory bulbectomized mice.

Olfactory bulbectomized (OBX) mice showed significant impairment of learning and memory-related behaviors 14 days after olfactory bulbectomy, as measured by passive avoidance and Y-maze tasks. We here observed a large impairment of hippocampal long-term potentiation (LTP) in the OBX mice. Concomitant with decreased acetylcholinesterase expression, protein kinase C (PKC)alpha autophosphorylation and NR1(Ser-896) phosphorylation significantly decreased in the hippocampal CA1 region of OBX mice. Both PKCalpha and NR1(Ser-896) phosphorylation significantly increased following LTP in the control mice, whereas increases were not observed in OBX mice. Like PKC activities, calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation significantly decreased in the hippocampal CA1 region of OBX mice as compared with that of control mice. In addition, increased CaMKII autophosphorylation following LTP was not observed in OBX mice. Finally, the impairment of CaMKII autophosphorylation was closely associated with reduced pGluR1(Ser-831) phosphorylation, without change in synapsin I (site 3) phosphorylation in the hippocampal CA1 region of OBX mice. Taken together, in OBX mice NMDA receptor hypofunction, possibly through decreased PKCalpha activity, underlies decreased CaMKII activity in the post-synaptic regions, thereby impairing LTP induction in the hippocampal CA1 region. Both decreased PKC and CaMKII activities with concomitant LTP impairment account for the learning disability observed in OBX mice.

Acetylcholine↗

PubMed2006

Anti-inflammatory effect of propolis through inhibition of nitric oxide production on carrageenin-induced mouse paw edema.

The anti-inflammatory effect of propolis was compared with that of diclofenac, a non-steroidal anti-inflammatory drug, and L-N(G)-nitro arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, using carrageenin-induced mouse paw edema. When administered 10 min prior to carrageenin injection, propolis (1 : 1000, 1 : 100, p.o.), diclofenac (12.5, 50 mg/kg, p.o.) and L-NAME (10, 100 mg/kg, s.c.) showed a significant anti-inflammatory effect. The anti-inflammatory effects of propolis and L-NAME were significantly inhibited by L-arginine, a precursor of nitric oxide, but not by D-arginine. In contrast, the anti-inflammatory effect produced by diclofenac was not inhibited by either D-arginine or L-arginine. These results indicate that the anti-inflammatory effect of propolis on mouse paw edema acts via the inhibition of nitric oxide production, similar to that of L-NAME but not diclofenac.

Animals↗

PubMed2005

Differential effects of N-peptidyl-O-acyl hydroxylamines on dynorphin-induced antinociception in the mouse capsaicin test.

In the capsaicin test, intrathecal (i.t.) dynorphins are antinociceptive. Cysteine protease inhibitors such as p-hydroxymercuribenzoate (PHMB) given i.t. augment and prolong their activity. The effect of two novel cysteine protease inhibitors, N-peptidyl-O-acyl hydroxylamines, on the antinociception induced by i.t. administered dynorphin A or dynorphin B has been investigated. When administered i.t. 5 min before the injection of capsaicin (800 ng) into the plantar surface of the hindpaw, dynorphin A (62.5-1000 pmol) or dynorphin B (0.5-4 nmol) produced a dose-dependent and significant antinociceptive effect. The effect of dynorphin A (1 nmol) and dynorphin B (4 nmol) disappeared completely within 180 and 60 min, respectively. PHMB (2 nmol) and Boc-Tyr-Gly-NHO-Bz (BYG-Bz) (2 nmol) co-administered with dynorphin A or dynorphin B significantly prolonged antinociception induced by both. On the other hand, Z-Phe-Phe-NHO-Bz (ZFF-Bz) (1 and 2 nmol) only prolonged antinociception induced by dynorphin A. The results suggest that Z-Phe-Phe-NHO-Bz is an inhibitor of cysteine proteases preferring cleavage of dynorphin A, with less specificity towards dynorphin B in the mouse spinal cord.

Analgesics↗

PubMed2005

Alterations in cognitive function in prepubertal mice with protein malnutrition: relationship to changes in choline acetyltransferase.

We have found that protein malnutrition (PM) causes a significant impairment of memory-related behavior on the 15th and 20th day after the start of PM (5% casein) feeding in prepubertal mice but not in postpubertal mice, as measured by a passive-avoidance task. This impairment was almost completely reversed by merely switching to a standard protein (20% casein) diet on the 10th day after the start of PM. However, the reversal was not observed when the switching to a standard protein regimen was done on the 15th day of the PM diet. Interestingly, the impairment of memory-related behavior on the 20th day was improved by the chronic administration of physostigmine (0.1 mg/kg/day x last 10 days, i.p.), a cholinesterase inhibitor. To correlate brain cholinergic neuron function with the memory-related behavior impairment induced by PM, microphotometry was used to determine the histological distribution of the imunofluorescence intensity for choline acetyltransferase (ChAT), a functional marker of presynapse in cholinergic neurons. The change in the intensity of fluorescence indicated that ChAT protein was decreased in the hippocampus (CA1, CA3 and dentate gyrus) on the 20th day after PM feeding in comparison with controls. These results suggest the possibility that the memory-related behavior deficits observed in prepubertal mice with PM are caused by a dysfunction of the cholinergic neurons in the hippocampus.

Age Factors↗

PubMed2005

Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities.

cAMP response element (CRE) transcription is dysregulated in neurodegenerative disorders in the central nervous system (CNS), including polyglutamine diseases. As the first step to find natural compounds with protective action against neurodegeneration in the CNS, we here examined whether six citrus flavonoids, namely nobiletin, 5-demethylnobiletin, tangeretin, sinensetin, 6-demethoxytangeretin, and 6-demethoxynobiletin, stimulated CRE-dependent transcription and induced neurite outgrowth in PC12D cells. Among the compounds, nobiletin most potently enhanced CRE-dependent transcription and neurite outgrowth by activating ERK/MAP kinase-dependent signalling to increase CREB phosphorylation. The transcription and neurite outgrowth were stimulated by nobiletin in a concentration-dependent manner, with a strong correlation between them. Furthermore, a 11-day oral administration of nobiletin rescued impaired memory in olfactory-bulbectomized mice documented to be accompanied by a cholinergic neurodegeneration. These results suggest that nobiletin with the activity to improve impaired memory may become a potential leading compound for drug development for neurodegenerative disorders exhibiting the dysregulated CRE-dependent transcription.

Animals↗

PubMed2005

Pronociceptive role of dynorphins in uninjured animals: N-ethylmaleimide-induced nociceptive behavior mediated through inhibition of dynorphin degradation.

Intrathecal (i.t.) administration into mice of N-ethylmaleimide (NEM), a cysteine protease inhibitor, produced a characteristic behavioral response, the biting and/or licking of the hindpaw and the tail along with slight hindlimb scratching directed toward the flank. The behavior induced by NEM was inhibited by the intraperitoneal injection of morphine. We have recently reported that dynorphin A and, more potently big dynorphin, consisting of dynorphins A and B, produce the same type of nociceptive response whereas dynorphin B does not [Tan-No K, Esashi A, Nakagawasai O, Niijima F, Tadano T, Sakurada C, Sakurada T, Bakalkin G, Terenius L, Kisara K. Intrathecally administered big dynorphin, a prodynorphin-derived peptide, produces nociceptive behavior through an N-methyl-d-aspartate receptor mechanism. Brain Res 2002;952:7-14]. The NEM-induced nociceptive behavior was inhibited by pretreatment with dynorphin A- or dynorphin B-antiserum and each antiserum also reduced the nociceptive effects of i.t.-injected synthetic big dynorphin. The characteristic NEM-evoked response was not observed in prodynorphin knockout mice. Naloxone, an opioid receptor antagonist, had no effects on the NEM-induced behavior. Ifenprodil, arcaine and agmatine, antagonists at the polyamine recognition site on the N-methyl-D-aspartate (NMDA) receptor ion-channel complex, and MK-801, an NMDA ion-channel blocker inhibited the NEM-induced effects. Ro25-6981, an antagonist of the NMDA receptor subtype containing NR2B subunit was not active. NEM completely inhibited degradation of dynorphin A by soluble and particulate fractions of mouse spinal cord. Collectively, the results demonstrate that endogenous prodynorphin-derived peptides are pronociceptive in uninjured animals, and required for the NEM-induced behavior. The NEM effects may be mediated through inhibition of the degradation of endogenous dynorphins, presumably big dynorphin that in turn activates the NMDA receptor ion-channel complex by acting on the polyamine recognition site.

Agmatine↗

PubMed2005

Effect of a nutritive-tonic drink on scopolamine-induced memory impairment in mice.

The effects of a liquid nutritive and tonic drug (NTD) selected from a modification of the "Kai-xin-shou-yu-shen-qi-wan" prescription, on scopolamine-induced amnesia in mice were investigated using the passive avoidance and water-maze tasks. A popular NTD in Japan that contains 17 crude (natural) drug extracts together with synthetic drugs such as taurine, caffeine, various vitamins and ethanol, and the natural drug extracts is based on a prescription of "Kampo" origin in Chinese medicine. Scopolamine (0.4 mg/kg, i.p.) reduces the step-through latency of the passive avoidance test and fear reaction behavior at 24 and 48 h after treatment. A single oral administration of the NTD (10 ml/kg) increased the step-through latency and the fear reaction behavior score in scopolamine-treated mice. Administration of the natural drug extracts found in the NTD tended to extend the step-through latency in the retention test at 48 h, but not 24 h after the initial scopolamine trial. However, administration of the synthetic drugs found in the NTD did not improve either the step-through latency or the behavioral score. The NTD and the natural drug extracts also improved the scopolamine-induced spatial memory impairment as assessed using the Morris water-maze test. In contrast, the synthetic drugs did not affect the escape latencies. Both NTD and the synthetic drugs increased the locomotor activity in scopolamine-treated mice, whereas the natural drug extracts did not. These results suggest that NTD improves scopolamine-induced amnesia, and that this action is attributable to the natural drug extracts in the NTD.

Animals↗

PubMed2004

Antinociceptive effect of different types of calcium channel inhibitors and the distribution of various calcium channel alpha 1 subunits in the dorsal horn of spinal cord in mice.

To understand better which voltage-dependent calcium channels (VGCCs) are involved in nociceptive neurotransmission, we investigated the pharmacological properties and distribution of VGCCs in the mouse spinal cord. A behavioral assay revealed that intrathecal injections of omega-agatoxin TK, omega-agatoxin IVA, omega-conotoxin GVIA, and SNX-482, which block P/Q-, P/Q-, N-, and R-type calcium channels, respectively, produced analgesic effects, while an L-type channel blocker had no such effect. An electrophysiological study demonstrated the presence of various types of VGCCs within dorsal root ganglion (DRG) neurons. Immunohistochemistry revealed distinct localization of P/Q-, N-, L-, and R-type calcium channel subunits to the dorsal horn of the spinal cord. The results of this study revealed the localization and functions of several calcium channels that are involved in nociceptive neurotransmission within the dorsal horn of the mouse spinal cord.

Analgesics↗

PubMed2004

Inhibitory effect of pranidipine on N-type voltage-dependent Ca2+ channels in mice.

We investigated the N-type voltage-dependent calcium channel blocking action of pranidipine, a novel dihydropyridine (DHP) derivative. Pranidipine significantly suppressed KCl-induced intracellular calcium changes ([Ca(2+)](i)) in a dose-dependent fashion in dorsal root ganglion neurons. A patch-clamp investigation revealed a dose-dependent blocking effect on N-type currents. Intrathecal injection of pranidipine significantly shortened the licking time in the late phase of the formalin test, as occurs with cilnidipine and amlodipine, which act on L- and N-type channels. Conversely, nicardipine, which acts exclusively on L-type channels, had no antinociceptive effect. Our results indicate that pranidipine inhibits N-type calcium channels. Furthermore, it exerts an antinociceptive effect, which might be related to an attenuation of synaptic transmission by nociceptive neurons due to the blocking effect of pranidipine on N-type calcium channels in primary nociceptive afferent fibers.

Animals↗

PubMed2004

Nociceptive behavior induced by poly-L-lysine and other basic compounds involves the spinal NMDA receptors.

We have previously shown that spermine, a basic polyamine, and big dynorphin, a basic polypeptide, induce nociceptive behavior if injected intrathecally (i.t.) in mice (see [Pain 86 (2000) 55-61] and [Brain Res. 952 (2002) 7-14]). This suggests that other basic molecules might have the same effects. Here, i.t. administration of poly-L-lysine (12 and 36 pg) to mice was found to produce the same characteristic behavioral response, biting and/or licking of the hindpaw and the tail along with slight hindlimb scratching directed toward the flank, which peaked at 0-10 min after injection. The behavior induced by poly-L-lysine (12 pg) was dose-dependently inhibited by intraperitoneal injection of morphine (0.25-4 mg/kg) and also dose-dependently, by i.t. co-administration of D-(-)-2-amino-5-phosphonovaleric acid (D-APV) (1-4 nmol), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine hydrogen maleate (MK-801) (0.0156-4 nmol), an NMDA ion-channel blocker, and ifenprodil (2-8 nmol), an antagonist of the polyamine recognition site and the NR2B-containing NMDA receptor subtype. On the other hand, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA glutamate receptor antagonist, 7-chlorokynurenic acid, a competitive antagonist of the glycine recognition site on the NMDA receptor ion-channel complex, [D-Phe7, d-His9]-substance P (6-11), a specific antagonist for substance P (NK1) receptors, or MEN-10,376, a tachykinin NK2 receptor antagonist, had no effect. These results confirm the observations obtained with other basic molecules and suggest that the behavior induced by poly-l-lysine is mediated through the activation of the NMDA receptor ion-channel complex acting either on the polyamine recognition site or on the NR2B subunit.

Analysis of Variance↗

PubMed2004

Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha-methylated substrate derivatives.

It is well known that head-twitch response (HTR) in mice represents hallucinations, since administration of lysergic acid diethylamide (LSD) produces hallucinations in humans, and the HTR in mice is induced by administration of LSD as a hallucinogen. The HTR is produced by excitation of 5-hydroxytryptamine (5-HT)2A receptors. In this paper, we review the mechanisms of HTR induced by various drugs such as 5-HT precursor, 5-HT receptor agonist, 5-HT releaser, hallucinogenic compounds, benzodiazepins and cannabinoid. The response induced by HTR-inducers is significantly enhanced by combined treatment with a non-selective form of monoamine oxidase (MAO) inhibitor. Thus, the relationship between MAO activity and HTR caused by these drugs (especially, alpha-methylated analogous compounds which 5-fluoro-alpha-methyltryptamine, 6-fluoro-alpha-methyltryptamine and p-hydroxyamphetamine) is presented in detail.

Animals↗

PubMed2004

Effect of a nutritive-tonic drink on stress-induced serum glucocorticoid in the mouse.

We evaluated stress during "restraint with gnawing (R+G+)" and "restraint without gnawing (R+G-)" in a mouse system. R+G- induced a higher serum glucocorticoid level than R+G+. Zena F-III (a nutritive-tonic drink prescribed as "Kampo", a traditional Japanese medicine with its origin in Chinese medicine) reduced the glucocorticoid elevation in R+G+, but not in R+G-. These results support the hypotheses that (i) activity, such as gnawing, which potentially leading to escape from distress, reduces the severity of emotional distress and (ii) Zena F-III reduces the severity of mental or emotional fatigue, or increases motivation, in a stressful situation that the animal can manage itself.

Animals↗

PubMed2004

Inhibitory effect of propolis on the growth of human leukemia U937.

We have investigated the effect of propolis (CB Propolis) on the growth of human histiocytic lymphoma U937 cells. We found that propolis strongly inhibited the growth of the cells and macromolecular synthesis in a dose- and time-dependent manner by apoptosis. Propolis at 0.015-0.5 microl/ml showed antitumor activity with an IC(50) of 0.18 microl/ml for 3 d. It also inhibits DNA, RNA and protein synthesis with an IC(50) of 0.08, 0.17 and 4.3 microl/ml, respectively. The inhibitory effect on DNA synthesis was partially irreversible. Moreover, an apoptotic DNA ladder and chromatin condensation were observed in the same concentration range in which cell growth was inhibited. The caspase inhibitor, Z-Asp-CH(2)-DCB, prevented DNA fragmentation. These results suggest that the antitumor activity of propolis occurs through the induction of apoptosis. Propolis may be useful as a cancer chemopreventive and chemotherapeutic agent.

Antineoplastic Agents↗

PubMed2004

[Dysfunction of serotonergic systems in thiamine-deficient diet fed mice: effects of SSRI on abnormality induced by thiamine deficiency].

Mice fed a thiamine deficient (TD) diet, showed some abnormal behaviors such as amnesia and mood abnormality. It is known that several neurons, especially marked in serotonergic neuron, are damaged in humans and rodents in the earlier phase of TD. The symptoms derived from dysfunction of serotonergic neurons are observed in Wernicke-Korsakoff patients (WKS)-derived TD, and it is known that fluvoxamine is effective for WKS. However, the mechanism of this dysfunction is still unclear. For that reason, we studied the relative mechanism between abnormal behaviors and selective dysfunction of serotonergic neurons in TD animals. As a result, this dysfunction by TD is much affected by the brainstem region. But the effect of fluvoxamine on depressive symptoms in WKS patients is not reported; therefore we also studied the effects of fluvoxamine on the depressive behaviors in TD mice as a model of WKS. The increase of immobility time in a forced swimming test as depressive behavior in TD mice was significantly inhibited by fluvoxamine, suggesting an improvable effect on depressive symptoms. With those results of ours, the possible mechanisms between the abnormal behaviors derived from the dysfunction of serotonergic neurons and the role of serotonin in TD and WKS are reviewed here.

Animals↗

PubMed2003

Immunohistochemical fluorescence intensity reduction of brain somatostatin in the impairment of learning and memory-related behaviour induced by olfactory bulbectomy.

The role of brain somatostatin (SST) on memory function after olfactory bulbectomy (OBX) was investigated by using the passive-avoidance task and immunohistochemical analyses in mice. The present study indicated that the learning and memory-related behaviour was impaired on the 7th and 14th day, but not on the 1st day after OBX. The impairment of learning and memory-related behaviour on the 14th day after OBX was dose-dependently reversed by intracerebroventricularly administered SST (1 microg per mouse). To ascertain the correlation between SST in mouse brain and the impairment of learning and memory-related behaviour induced by OBX, the immunohistochemical distribution of brain SST was determined by fluorescence intensity using two-dimensional microphotometry. The intensity of SST fluorescence was low in the hippocampus on the 14th day after OBX in comparison with Sham controls. These results suggest that SST in the hippocampus is related to the impairment of learning and memory-related behaviour induced by OBX.

Animals↗

PubMed2003

Characteristics of changes in cholinergic function and impairment of learning and memory-related behavior induced by olfactory bulbectomy.

Memory function after olfactory bulbectomy (OBX) was examined in two tasks, namely, step-through passive avoidance task and elevated plus-maze task. OBX mice showed a significant impairment of learning and memory-related behavior on the 7th and 14th day, as measured by passive avoidance task but not elevated plus maze task. The impairment of learning and memory-related behavior on the 14th day was improved by administration of the cholinesterase inhibitor physostigmine (0.1 mg/kg, i.p.), the non-selective muscarinic agonist oxotremorine (0.1 mg/kg, i.p.) or the selective muscarinic M(1) agonist McN-A-343 (10 microg/mouse, i.c.v.). In contrast, administration of the nicotinic agonist lobeline (5-9.8 mg/kg, i.p.) or the selective muscarinic M(2) antagonist methoctramine (2.25-18 microg/mouse, i.c.v.) has no effect on the impairment of learning and memory-related behavior induced by OBX. In addition, we have demonstrated that the intensity of choline acetyltransferase (ChAT) fluorescence is significantly decreased in the cortex, hippocampus and amygdala on the 14th day after OBX. These results suggest that the impairment of learning and memory-related behavior induced by OBX may be caused by degeneration of cholinergic neurons and muscarinic M(1) receptors play an important role in the improvement process.

Amygdala↗