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H Kametani

Publications and source records attributed to H Kametani.

At least 19 recordsLinked to original sources
PubMed1998

Age-associated memory impairment. Assessing the role of nitric oxide.

Several neurotransmitter systems have been investigated to assess hypothesized mechanisms underlying the decline in recent memory abilities in normal aging and in Alzheimer's disease. Examining the performance of F344 rats in a 14-unit T-maze (Stone maze), we have focused on the muscarinic cholinergic (mACh) and the N-methyl-D-aspartate (NMDA) glutamate (Glu) systems and their interactions. Maze learning is impaired by antagonists to mACh or NMDA receptors. We have also shown that stimulation of mACh receptors can overcome a maze learning deficit induced by NMDA blockade, and stimulation of the NMDA receptor can overcome a similar blockade of mACh receptors. No consistent evidence in rats has been produced from our laboratory to reveal significant age-related declines in mACh or NMDA receptor binding in the hippocampus (HC), a brain region that is greatly involved in processing of recent memory. Thus, we have directed attention to the possibility of a common signal transduction pathway, the nitric oxide (NO) system. Activated by calcium influx through the NMDA receptor, NO is hypothesized to be a retrograde messenger that enhances presynaptic Glu release. Maze learning can be impaired by inhibiting the synthetic enzyme for NO, nitric oxide synthase (NOS), or enhanced by stimulating NO release. However, we have found no age-related loss of NOS-containing HC neurons or fibers in rats. Additionally, other laboratories have reported no evidence of an age-related loss of HC NOS activity. In a microdialysis study we have found preliminary evidence of reduced NO production following NMDA stimulation. We are currently working to identify the parameters of this phenomenon as well as testing various strategies for safely stimulating the NO system to improve memory function in aged rats.

Aging↗
PubMed1998

Intracerebroventricular injection of N omega-nitro-L-arginine in rats impairs learning in a 14-unit T-maze.

We investigated whether intracerebroventricular (i.c.v.) infusion of the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine (N-Arg), impairs learning in male Sprague-Dawley rats (2-3 months old) in a 14-unit T-maze. Rats were pretrained in one-way active avoidance to a criterion of 13/15 avoidances of foot shock in a straight runway. The next day, rats received i.c.v. injections of either artificial cerebrospinal fluid (aCSF) as controls or N-Arg (12 microg or 15 microg) 30 min before training in the 14-unit T-maze. The learning contingency was to negotiate each of 5 segments within 10 s to avoid footshock during 15 trials. Performance variables included errors (deviations from the correct pathway), runtime from start to goal, and shock frequency and duration. Compared to controls, the number of errors over the last 10 trials was higher in rats receiving 15 microg N-Arg and over the last 5 trials for those given 12 microg. Runtime, shock frequency and duration were increased in both N-Arg groups. The N-Arg-induced (15 microg i.c.v.) impairment could be attenuated when the nitric oxide donor, sodium nitroprusside (1 mg/kg), was administered intraperitoneally 1 min prior to maze learning. In a retention test, rats were treated with either aCSF or 15 microg N-Arg i.c.v. 30 min before being retested in the maze 7-10 d following acquisition training. Under these conditions, maze performance was not significantly affected. These results confirmed previous findings that inhibition of nitric oxide synthase impairs acquisition but not retention. Moreover, the N-Arg-induced learning impairment does not appear to be related to noncognitive aspects of performance.

Analysis of Variance↗
PubMed1993

Impaired acquisition in a 14-unit T-maze following medial septal lesions in rats is correlated with lesion size and hippocampal acetylcholinesterase staining.

Septohippocampal cholinergic system involvement in acquisition of an aversively motivated 14-unit T-maze was evaluated in 4-month-old male Fischer-344 rats. Each rat was assigned to one of two groups that received either a bilateral electrolytic lesion to the medial septal area (MSA) or a sham operation. One week after surgery, each rat began pretraining in one-way active avoidance (footshock = 0.8 mA) consisting of 10 trials per day on each of 3 consecutive days. Criterion for successful completion of pretraining was 8/10 avoidances on the third day. On the day following completion of pretraining, each rat received 10 trials in a shock-motivated 14-unit T-maze. The performance requirement was to move through each of five maze segments within 10 s to avoid footshock (0.8 mA). A second 10-trial session was provided 24 h later. Performance measures included errors, alternation errors, runtime, shock frequency, and duration. Following maze training, each rat was sacrificed, and formalin-fixed brains were frozen for histology, which included procedures for thionin Nissl and acetylcholinesterase (AChE) staining. MSA-lesioned rats were observed to be significantly impaired on all measures of maze performance compared to sham-operated controls. Densitometric analysis of hippocampal AChE staining revealed a 30% reduction in relative AChE staining of MSA-lesioned rats compared to sham-operated controls. Lesion size was observed to be highly positively correlated with maze errors. A negative correlation of mean error score with density of AChE staining was observed for MSA-lesioned rats, but not for sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1991

Circadian rhythm of cortical acetylcholine release as measured by in vivo microdialysis in freely moving rats.

Circadian changes in cortical acetylcholine (ACh) release were examined in freely moving rats using long-term in vivo microdialysis and high performance liquid chromatography with electrochemical detection. A microdialysis probe was implanted into the frontal cortex and a dialysate was collected every 30 min for two or three days under a 12 h light/dark (LD 12:12) cycle and for the succeeding 2 or 3 days under constant dark (DD) conditions. When animals were exposed to the LD cycle, dialysate concentrations of ACh showed a clear circadian rhythmicity with the highest peak in the dark phase and the lowest peak in the light phase. The mean cortical ACh release during the dark phase under the LD cycle was approximately 33% higher than that during the light phase. Under DD conditions, circadian changes in ACh release persisted with similar amplitudes as observed in the LD condition. These results suggest that cortical ACh release is under the control of a circadian oscillator.

Acetylcholine↗
PubMed1990

Alterations in acetylcholine release in the rat hippocampus during sleep-wakefulness detected by intracerebral dialysis.

Acetylcholine (ACh) release from the dorsal hippocampus was continuously monitored in freely moving rats during a light period using an intracerebral dialysis technique. A dialysate was collected every 6 min and polygraph recordings including cortical and hippocampal electroencephalograms, electromyogram, and electrooculogram were simultaneously made to determine the stage of sleep-wakefulness. The content of ACh was measured by high-performance liquid chromatography with electrochemical detection. ACh output showed profound and state-dependent fluctuations. ACh levels during waking increased approximately 300% compared to slow wave sleep. In contrast, the rate of ACh release during paradoxical sleep was as high as during waking and appeared to be even higher. These results revealed that the intracerebral dialysis technique provides a useful method to monitor changes in spontaneous neurotransmitter release during the sleep-waking cycle.

Acetylcholine↗
PubMed1990

Parietal cortex lesions do not impair retention performance of rats in a 14-unit T-maze unless hippocampal damage is present.

Young male F-344 rats, pretrained in a straight runway to avoid shock, were then trained in a shock-motivated 14-unit T-maze. One day after maze acquisition, extensive parietal cortex lesions (PC) or sham operations (CON) were performed to assess possible involvement of parietal cortex in the age-related impairment previously observed in this task. Twelve days after surgery, a first 10-trial retention session in the 14-unit T-maze was conducted. One day later the vibrissae of half the rats in each group were clipped to examine involvement of the damaged barrel cortex field in maze performance of rats with PC lesions. The following day a second 10-trial retention session occurred. Finally, retention of the straight runway avoidance response was tested. Histological verification revealed a group with consistent parietal damage but also a subgroup with relatively small lesions to dorsal or lateral hippocampus in addition to parietal damage (PC + HIP). Behavioral results revealed virtually perfect maze retention for CON and PC rats. In contrast, PC + HIP rats were severely impaired in maze retention performance. Retention of the straight runway avoidance response was perfect in CON and PC rats but was impaired in PC + HIP rats. Vibrissae clipping did not affect error performance in the maze but led to a transitory increase in runtime. Overall, the results indicate that parietal lobe damage shortly after acquisition does not impair retention performance of young rats in the 14-unit T-maze, unless hippocampal damage is also evident. Thus, parietal lobe dysfunction alone would not appear to be involved in the age-related retention impairment previously observed in this task.

Aging↗
PubMed1989

Comparison of retention performance between young rats with fimbria-fornix lesions and aged rats in a 14-unit T-maze.

Young (3-months) and aged (24-months) male F-344 rats were pretrained in one-way active avoidance in a straight runway for 3 days. Then two 10-trial daily sessions were given in a 14-unit T-maze in which the response requirement was to negotiate each of 5 maze segments within 10 s to avoid footshock. One day or one week after acquisition, bilateral electrolytic lesions were made in the fimbria-fornix of young rats (1-day lesion or 1-week lesion). Corresponding sham operations were made for remaining young rats (1-day sham or 1-week sham). Aged animals did not receive any surgical treatment. One week after surgery, a 10-trial retention test was conducted to assess the lesion effects on retention and to manipulate the interval between acquisition and lesions. Aged animals were tested in the maze 1 week after acquisition. Results revealed that rats with fimbria-fornix lesions exhibited significant impairment compared to sham-operated groups on all retention performance measures including errors, runtime, number of shocks, duration of shock, and alternation errors. The number of errors and alternation errors of lesioned animals were still higher than those of sham-operated animals at the second half of the retention test, whereas other non-cognitive measures for lesioned animals recovered to control levels. The interval between acquisition training and lesions had no influence on retention performance. Although performance of aged rats during acquisition and retention trials was significantly worse than that of young controls and lesioned animals, a similar recovery pattern during retention testing was found for young rats with fimbria-fornix lesions and aged rats, i.e. both groups showed significant declines in non-cognitive measures with less decline in cognitive measures. These results suggest that the fimbria-fornix is partially involved in retention of 14-unit T-maze performance and that the age-related retention deficit observed in this task may be related to impaired transmission through this pathway.

Aging↗
PubMed1989

Retrospective and prospective coding of information: dissociation of parietal cortex and hippocampal formation.

Animals with sham operations, hippocampal formation, or small and large parietal cortex lesions were trained in a task that required memory for short or long lists of items (spatial locations). More specifically, on any one trial, a rat is presented with 2, 4, 6, 8, or 10 items (spatial locations) on a 12-arm radial maze followed 15 min later by a win-shift test that required the animal to choose between a place previously visited and a novel place. Sham-operated animals showed an increase in errors as a function of set size (2 to 8 items) followed by a decrease in errors with a set size of 10 items, suggesting the use of both retrospective and prospective memory codes. In contrast, animals with hippocampal formation lesions made errors for all set sizes, reflecting an inability to use a retrospective and prospective memory code. The failure to use a prospective code is probably a function of the inability to use a retrospective code (i.e., the animal needs to remember first what has occurred before it can determine what information lies ahead). Animals with small or large parietal cortex lesions made most of their errors for the longest list length, reflecting an inability to shift from a retrospective to prospective memory code. This dissociation between the hippocampal formation and parietal cortex might reflect mediation of different memory operations. The hippocampal formation might mediate new incoming information (data-based memory processing) and thus accentuate the importance of a retrospective memory code. The parietal cortex might mediate existing knowledge (expectancy-based memory processing) and thus facilitate the utilization of a prospective memory code.

Animals↗
PubMed1988

Peripheral neuropathy with predominantly motor manifestations in a patient with carcinoma of the uterus.

An autopsy case of a 56-year-old woman who had carcinoma of the corpus uteri and peripheral neuropathy with predominantly motor manifestations is described. The neurological abnormalities included subacute weakness of the limbs and loss of deep reflexes, which improved after the surgical removal of the uterine carcinoma. Neuropathologically, peripheral nerves mainly presented features of axonal degeneration with a mild loss of myelinated fibres. Anterior horns of the spinal cord showed central chromatolysis of the motor nerve cells and many spheroids without neuronal loss. Axonopathy of peripheral nerves was considered to be the main pathological process in this paraneoplastic syndrome.

Carcinoma↗
PubMed1988

Age difference of response strategy in radial maze performance of Fischer-344 rats.

Age and sex differences in learning performance in an 8-arm radial maze were examined in Fischer-344 rats (aged: 22-27 months; young: 3-4 months). Results of total responses and initial correct responses showed impaired performance in aged rats. There was a sex difference only in initial correct responses of the aged group. In agreement with findings of previous studies, these results demonstrated deficits of spatial learning performance in aged rats. A response strategy was examined as a factor which may affect radial maze performance. Our results revealed that age groups utilized different response strategies to solve the task and appeared similar to reports of maze performance of young animals with experimentally impaired cholinergic function. The results suggest that age difference in a response strategy is due to deterioration of cholinergic system in aged rats, and factors which may have a relationship with the impaired performance in aged rats were discussed, including alteration of response strategy.

Aging↗
PubMed1987

Delayed memory dysfunction by transient hypoxia, and its prevention with forskolin.

Rats exposed to 40 min hypoxia 3 h before a one-trial learning passive avoidance task showed impaired memory retention 24 h later. this model was used to assess the ability of forskolin to restore the delayed memory dysfunction. Significant amelioration of memory retention was observed when forskolin (500 micrograms/kg, i.p.) was injected just after hypoxia. Forskolin is suggested to enhance cerebral blood flow and to facilitate memory function through the action of increased cyclic adenosine monophosphate (cAMP).

Animals↗
PubMed1984

Increased novelty-induced grooming in aged rats: a preliminary observation.

Age-related changes in grooming activity in female Fischer-344 rats were observed in a home cage and in a novel testing chamber for 50 min. Compared to the home cage condition with brief handling treatment, excessive grooming was found in the novel situation. The amount of novelty-induced grooming of aged rats (26-28 months) was about two times that of young animals (6-8 months). This increase in novelty-induced grooming of aged animals was attributable to an increase in the number of grooming bouts, prolongation of each grooming bout, and a slight increase in the duration of licking elements. However, there were no age differences in the percentage of face washing and the duration of face-washing elements. These results are discussed in terms of behavioral aging and age-related changes in peptidergic pathways in the brain.

Aging↗
PubMed1983

The reversal effect of antidepressants on the escape deficit induced by inescapable shock in rats.

This experiment investigated the effect of antidepressants on the escape deficit induced by inescapable shock. Following exposure to escapable shock, rats received a single injection of either tricyclic antidepressants (imipramine, desipramine), an atypical antidepressant (nomifensine), or saline. In a subsequent two-way shuttle test, treatments with these antidepressants reversed the escape deficit of the "inescapable-shock" groups without affecting performance of the "escapable-shock" groups. It is suggested that catecholamine re-uptake inhibition of the acute actions of antidepressants contributed to this reversal effect. The findings are discussed in relation to the neurochemical hypothesis of the escape deficit induced by inescapable shock and to an animal model of depression.

Animals↗
PubMed1982

A new behavioral test for antidepressant drugs.

In 1977 Porsolt proposed a new behavioral test, using mice, for screening antidepressants. He stated that antidepressants selectively reduce the immobility of mice in a forced swimming situation. The test is useful, but lacks objectivity in its evaluation of immobility and does not successfully screen 'false positive' drugs. A new 'behavioral despair' test was thus designed involving a small water wheel set in a water tank. Mice placed on this apparatus turned the wheel vigorously but, when they abandoned attempts to escape from the water the wheel stopped turning. The number of rotations of the water wheel were counted. All antidepressants tested increased the number of rotations. However, tranquillizers, anticholinergics and antihistaminics were not effective. We suggest that this water wheel test is more appropriate as screening test for antidepressants than Porsolt's test with regard to both objectivity and specificity.

Animals↗
PubMed1982

[Psychobiological study of habituation to stress--observation of behavioral and neurochemical changes].

The effect of acute and chronic stress on escape behavior, brain norepinephrine (NE) concentration and beta-receptor binding was examined, and the mechanism of adaptation to chronic stress was discussed in terms of both behavioral and neurochemical standpoint. The rats were divided into an acute stress group (AS), chronic stress group (CS) and control group (C). The rats of AS experienced a single stress session. The rats of CS received 5 separate sessions. The rats of each group were examined by escape test, or killed for the purpose of measurement of beta-receptor binding and NE concentration 30 min after the final shock. The latency of escape test of AS was significantly greater than that of C. On the other hand, the latency of CS, and cortex beta-receptor binding of CS was significantly lower than that of C. However, beta-receptor binding of hypothalamus of AS and CS was not different from that of C. These results indicate that adaptation to chronic stress occurs with respect to escape behavior, and its neurochemical background relates with the acceleration of NE turnover and down regulation of beta-receptor sensitivity of cerebral cortex.

Animals↗
PubMed1979

Neural mechanisms of reflex facilitation and inhibition of gastric motility to stimulation of various skin areas in rats.

1. Experiments were performed on chloralose-urethane anaesthetized rats to determine the involvement of extrinsic gastric autonomic nerves in reflex facilitation and inhibition of gastric motility when mechanical nociceptive stimulation was delivered to either hind paw or abdominal skin, respectively. 2. After bilaterally sectioning the splanchnic nerves in vagal intact animals, the reflex facilitation of gastric motility produced by hind paw stimulation persisted, but the reflex inhibition previously produced by abdominal skin stimulation disappeared. 3. Hind paw stimulation increased efferent activity of the gastric branch of the vagus nerve, but stimulation of abdominal skin had little influence. 4. Bilateral vagotomy in splanchnic nerve intact animals did not influence the gastric reflex inhibition by abdominal skin stimulation, but either abolished gastric reflex facilitation produced by hind paw stimulation or reversed the reflex facilitation response to slight reflex inhibition. 5. Efferent activity of the gastric sympathetic nerve was greatly increased by abdominal skin stimulation, and was either slightly increased or not influenced by hind paw stimulation. 6. It was concluded that reflex increase of efferent activity of the gastric vagi was responsible for the gastric motility facilitation produced by hind paw stimulation, and also that reflexly increased efferent activity of the gastric sympathetic nerves resulted in gastric motility inhibition produced by abdominal skin stimulation. It is suggested efferents are inhibitory. 7. After spinal transection at the cervical level, the reflex facilitation of gastric motility previously produced by stimulation of a hind paw was completely abolished, or reversed to slight reflex inhibition, while reflex inhibition of gastric motility produced by stimulation of abdominal skin remained. It was concluded that the gastric reflex inhibition was a spinal reflex. 8. Interaction between reflex facilitation and inhibition of gastric motility during simultaneous stimulation of both hind paws and abdominal skin was observed as partial cancellation of each effect by the other. However, sympathetic reflex inhibition of gastric motility seemed to be much stronger than the vagal reflex facilitatory effect.

Animals↗