Hisae Matsuo

Analgesic effect of milnacipran is associated with c-Fos expression in the anterior cingulate cortex in the rat neuropathic pain model

The objective of the present study was to examine whether milnacipran, a serotonin-noradrenaline reuptake inhibitor, has an analgesic effect in rats with neuropathic pain. In addition, the c-Fos expression was investigated in the supraspinal sites of the brain and in the spinal dorsal horn in association with the nociceptive processing in rats with neuropathic pain produced by chronic constriction injury (CCI) in the sciatic nerve. In the CCI-induced neuropathic rats, behavioral testing for determining the change in the withdrawal threshold to mechanical stimulation and immunohistochemical detection of c-Fos were both performed. The anti-allodynic effect derived from milnacipran gradually increased over the observation period, indicating that the delayed-onset analgesia might be elicited by the continuous administration of milnacipran. The increased level of c-Fos expression in the anterior cingulate cortex (ACC) induced by noxious mechanical stimulation was significantly inhibited by the continuous administration of milnacipran, indicating that milnacipran might cause a functional modification in the nociceptive processing in the ACC.

Psychological prenatal stress reduced the number of BrdU immunopositive cells in the dorsal hippocampus without affecting the open field behavior of male and female rats at one month of age.

We examined whether prenatal psychological stress with little physical stress causes changes in the behavior and neurogenesis of the offspring of Sprague-Dawley rats at one month. Dams in the last trimester of gestation were psychologically stressed by placing them in a social communication box and shocking a rat on the other side of a transparent wall. They suffered little physical stress. Male and female offspring from the dams showed little change in an open field test at postnatal day (PND) 30. To evaluate neurogenesis in the brain, BrdU was intraperitoneally injected at PND 35 into offspring not used in the open field test. Immunohistochemical examinations of BrdU in their dorsal hippocampus at PNDs 42 and 112 revealed that the number of BrdU immunopositive cells in the offspring of prenatally stressed rats was significantly smaller than in the offspring of unstressed ones. These results together with our previous finding that prenatal psychological stress can alter specific behaviors suggest that prenatal psychological stress can suppress neurogenesis in the dorsal hippocampus of rats of both sexes at PND 35 even though impairment in the behavioral task has not yet appeared.

Development of the Psychiatric Nurse Job Stressor Scale (PNJSS)

Aims:  The aim of the present study was to develop a tool, the Psychiatric Nurse Job Stressor Scale (PNJSS), for measuring the stress of psychiatric nurses, and to evaluate the reliability and validity of the PNJSS.

Differential expression of FosB, c-Fos, and Zif268 in forebrain regions after acute or chronic l-DOPA treatment in a rat model of Parkinson's disease

A study was carried out to examine the effects of acute and chronic L-DOPA treatment on the distribution of the immediate-early gene (IEG) proteins (FosB, c-Fos, and Zif268) in forebrain regions in a unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinsons disease. During a course of chronic L-DOPA treatment (15 mg/day, 15 days), rats with a 6-OHDA lesion developed abnormal involuntary movements. Compared with the rats in the acute L-DOPA treatment group, those in the chronic treatment group had significantly more FosB-immunopositive cells in the anterior cingulate (Cg) and the dorsolateral caudate-putamen ipsilateral to the lesion and significantly fewer c-Fos-immunopositive cells in the Cg, the nucleus accumbens shell, and the basolateral nucleus of amygdala ipsilateral to the lesion. No significant difference was observed in the number of Zif268-immunopositive cells between the acute and chronic L-DOPA groups. In summary, differential expression of three IEG proteins was observed in the forebrain regions during a course of chronic L-DOPA treatment of 6-OHDA-treated hemiparkinsonian rats.

Burnout in Japanese residents and its associations with temperament and character

AIM High risk of burnout in healthcare workers has long been recognized. However, there are no methods to predict vulnerability to burnout. METHODS We examined whether temperament and character are associated with burnout and depressive state in residents by using the Temperament and Character Inventory (TCI). The TCI was used for residents at the beginning of clinical training and then the Maslach Burnout Inventory-General Survey (MBI-GS) and the Self-Rating Depression Scale (SDS) were administered at the beginning of clinical training and after four and ten months. Participants were 85 residents who started clinical training after graduating from the University of Miyazaki Hospital in April 2012 and 2013. RESULTS After ten months, 23.5% of participants were newly identified with burnout using the MBI-GS and 15.3% of participants were newly diagnosed with depressive state using the SDS. We found that residents with high Cooperativeness were significantly more prone to burnout and that residents with high Harm Avoidance and low Self-Directedness were significantly more prone to depressive states. CONCLUSIONS Our results suggest that the TCI can predict not only the risk for future depressive state but also the risk for future burnout. We feel it is important for the resident education system to identify residents with these temperament and character traits and to help high-risk residents avoid burnout and depressive state.

Effects of cabergoline and rotigotine on tacrine-induced tremulous jaw movements in rats.

OBJECTIVES We examined the effects of two dopamine agonists, cabergoline and rotigotine, on tacrine-induced tremor and c-Fos expression in rats. METHODS Rats received intraperitoneal injection of cabergoline (0.5, 1.0, or 5.0mg/kg), rotigotine (1.0, 2.5, or 10.0mg/kg), or vehicle 30min before intraperitoneal injection of tacrine (5.0mg/kg). The number of tremulous jaw movements (TJMs) after tacrine administration was counted for 5min. Animals were sacrificed 2h later under deep anesthesia, and the brain sections were immunostained in order to evaluate the c-Fos expression. RESULTS Induction of TJMs by tacrine was dose-dependently reduced by pretreatment with cabergoline and rotigotine. The number of c-Fos-positive cells was significantly enhanced in the medial striatum, nucleus accumbens core, and nucleus accumbens shell after tacrine administration, and the enhanced expression of c-Fos in these three regions was significantly attenuated by cabergoline, while rotigotine suppressed c-Fos expression in two regions except the nucleus accumbens core. CONCLUSIONS These results suggest that tacrine-induced TJMs would be relieved by either cabergoline or rotigotine and that anticholinesterase-induced TJMs and the ameliorating effects of dopamine agonists would relate to neuronal activation in the striatum and nucleus accumbens.

Differential expression of Fos and Zif268 in the nigrostriatal system after methamphetamine administration in a rat model of Parkinson's disease

The goal of this study was to examine the topological specificity of methamphetamine‐induced activation of the immediate‐early gene proteins, Fos and Zif268, in the nigrostriatal system in a unilateral 6‐hydroxydopamine (6‐OHDA) rat model of Parkinsons disease with or without intrastriatal grafts of fetal ventral mesencephalon. Methamphetamine (3 mg/kg, i.p.) induced Fos‐like immunoreactivity (FLI) dominantly in the striatum and the globus pallidus (GP) on the intact side as well as in the substantia nigra pars reticulata (SNr) on the lesioned side in the 6‐OHDA rats. Lower levels of methamphetamine‐induced FLI in the striatum and GP on the lesioned side were restored by intrastriatal grafts which could completely suppress the methamphetamine‐induced rotation. In the striatum, a similar tendency could be observed between Fos and Zif268 immunoreactivity following methamphetamine. However, sparse immunoreactivity of Zif268 could be detected in the GP and SNr on both sides in the 6‐OHDA rats. Intrastriatal grafts had little influence on Zif268 expression in these two regions. The differential expression of Fos and Zif268 was observed among the three regions of the nigrostriatal system following methamphetamine in the 6‐OHDA rats. This may suggest that Fos and Zif268 therefore possess gene‐specific and region‐specific functions in the basal ganglia nuclei. Synapse 62:920–926, 2008.

Distribution of hemokinin-1 in the rat trigeminal ganglion and trigeminal sensory nuclear complex

OBJECTIVE A new mammalian tachykinin peptide encoded in a TAC4 gene was identified and designated as hemokinin-1 (HK-1). A representative of the tachykinin peptide family is substance P (SP), and the function of SP has been well characterized as a pain transmitter or modulator, while it is possible that HK-1 is involved in pruriceptive processing, but, as yet, the distribution of HK-1 peptide in the trigeminal sensory system is still unknown. Thus, the aim of the present study was to elucidate the distribution of HK-1, while comparing the expression of SP, in the trigeminal ganglion and trigeminal sensory nuclear complex. DESIGN The trigeminal ganglion and the brain stem of male SD rats were used in the immunohistochemical study. Since the amino acid sequence in the carboxyl-terminal regions of HK-1 and SP is common, polyclonal antibodies of HK-1 and SP derived from 6 amino acids consisting of amino-terminal regions of these peptides were produced in guinea pig and rabbit, respectively. The immunohistochemical staining of HK-1 and SP was conducted using frozen sections of the trigeminal ganglion and brain stem in rats. RESULTS Immunohistochemical studies revealed the expression of HK-1 in small- and medium-sized trigeminal ganglion neurons, in the paratrigeminal nucleus, and in lamina I of the trigeminal nucleus caudalis, while there was no immunoreactivity of HK-1 in the trigeminal nucleus principalis, trigeminal nucleus oralis, and trigeminal nucleus interpolaris. CONCLUSION These findings indicate that HK-1 is a target molecule for treatment of itch in the orofaicial regions.

Intrastriatal grafts of fetal ventral mesencephalon improve allodynia-like withdrawal response to mechanical stimulation in a rat model of Parkinson's disease.

We previously reported that a unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinsons disease showed allodynia-like withdrawal response to mechanical stimulation of the ipsilateral side of the rat hindpaw. The goal of this study was to investigate the effect of intrastriatal grafts of fetal ventral mesencephalon (VM) on the withdrawal response in 6-OHDA rats. The withdrawal threshold in response to the mechanical stimulation of the rat hindpaw was measured using von Frey filaments. In the ipsilateral side of the 6-OHDA lesions, the withdrawal threshold in response to mechanical stimulation significantly increased in 6-OHDA rats with VM grafts compared with those with sham grafts, but did not change in the contralateral side at 5 weeks after transplantation. The present results suggest that the intrastriatal grafts of fetal VM may relieve pain sensation induced by mechanical stimulation in 6-OHDA rats.

Job-related stress in psychiatric nurses in Japan caring for elderly patients with dementia

ObjectivesWe investigated the specificity and structures of job-related stress in psychiatric dementia nurses (PDNs) caring for elderly patients with serious behavioral and psychological symptoms of dementia who required substantial assistance with activities of daily living, in order to obtain fundamental knowledge toward providing mental health care for these nurses.MethodsSubjects were 244 nurses [63 PDNs and 181 other psychiatric nurses (OPNs)]ResultsAnalysis of covariance to examine the specificity of job-related stress in PDNs revealed physical workload and work environment to be more significant stressors, and irritability and anxiety to be more significant stress reactions in PDNs than in OPNs. An examination of PDNs’ job-related stress structures established in a structural equation model with two stress reactions confirmed as specific outcomes for PDNs revealed a significant positive influence of work environment on irritability; utilization of techniques for anxiety and physical workload influenced both stress reactions.ConclusionsOur findings highlight the importance of reducing physical workload and environment and establishing a structure for nursing techniques in psychiatric dementia wards to improve the mental health of PDNs.