Hippocampal astrocytes are necessary for antidepressant treatment of learned helplessness rats.

The astrocyte is a major component of the neural network and plays a role in brain function. Previous studies demonstrated changes in the number of astrocytes in depression. In this study, we examined alterations in the number of astrocytes in the learned helplessness (LH) rat, an animal model of depression. The numbers of activated and nonactivated astrocytes in the dentate gyrus (molecular layer, subgranular zone, and hilus), and CA1 and CA3 regions of the hippocampus were significantly increased 2 and 8 days after attainment of LH. Subchronic treatment with imipramine showed a tendency (although not statistically significant) to decrease the LH-induced increment of activated astrocytes in the CA3 region and dentate gyrus. Furthermore, subchronic treatment of naïve rats with imipramine did not alter the numbers of activated and nonactivated astrocytes. However, the antidepressant-like effects of imipramine in the LH paradigm were blocked when fluorocitrate (a reversible inhibitor of astrocyte function) was injected into the dentate gyrus or CA3 region. Injection of fluorocitrate into naive rats failed to induce behavioral deficits in the conditioned avoidance test. These results indicate that astrocytes are responsive to the antidepressant-like effect of imipramine in the dentate gyrus and CA3 region of the hippocampus.

The prevalence of probable delayed-sleep-phase syndrome in students from junior high school to university in Tottori, Japan.

Delayed sleep phase syndrome (DSPS) is a circadian rhythm sleep disorder with a typical onset in the second decade of life. DSPS is characterized by the sleep-onset insomnia and the difficulty in waking at the desired time in the morning. Although DSPS is associated with inability to attend school, the prevalence has been controversial. To elucidate a change in the prevalence of DSPS among young population, epidemiological survey was conducted on Japanese students. A total of 4,971 students of junior high school, senior high school, and university were enrolled in this cross sectional study in Tottori Prefecture. They answered anonymous screening questionnaire regarding school schedule, sleep hygiene and symptomatic items of sleep disorders. The prevalence of probable DSPS was estimated at 0.48% among the total subject students without gender difference. In university, the prevalence of the last year students showed the highest value (1.66%), while that of the first year students showed the lowest value (0.09%) among all school years from junior high school to university. The prevalence increased with advancing university school years. Thus, a considerable number of Japanese students are affected with DSPS. Senior students of university are more vulnerable to the disorder than younger students. Appropriate school schedule may decrease the mismatch between the individual's sleep-wake cycle and the school schedule. Promotion of a regular sleep habit is necessary to prevent DSPS among this population.

Mouse brain IgG-like immunoreactivity: strain-specific occurrence in microglia and biochemical identification of IgG.

Unlike the brains of most mammals, the mouse brain appears unique in the massive appearance of cells showing IgG-like immunoreactivity, which has repeatedly been shown via immunohistochemistry. In the present study, we first examined possible species differences in IgG-like immunohistochemical staining in the brains of various rodents, including mice. In four of six mouse strains examined (ICR, Balb/c, C57BL/6, and AKR/J), antibodies against mouse IgG revealed positive staining in many brain microglia. However, no such positive staining was detected in brains of the rat, hamster, guinea pig, or two other mouse strains (CBA/N and CBA/J). We purified IgG-like-immunoreactive molecule(s) biochemically from brain of the ICR mouse as a representative mouse strain. Our amino-acid-sequence analysis proved that the purified protein was identical to serum IgG. The possibility of IgG synthesis by brain microglia in the ICR mouse was denied by our RT-PCR experiments and in situ hybridization histochemistry. In addition, Fcgamma-receptor-deficient double-knockout mice of the C57BL/6 genetic background contained no IgG-immunoreactive microglia in the brain. These results clearly indicate that microglial IgG staining is due to the uptake of serum IgG through Fcgamma receptors. However, the strain-specific mechanisms resulting in microglial IgG uptake remain to be elucidated, in that Fcgamma receptors are omnipresent in microglia of all rodents examined here.

Effects of acute administration of methamphetamine on Narp mRNA in rat brain.

Narp (neuronal activity-regulated pentraxin) is a secreted immediate early gene product functioning as a cluster factor for the AMPA receptor subtype of glutamate receptors. This study was designed to examine the effects of acute administration of methamphetamine (MAP) on the Narp gene in rat brain using reverse transcription - polymerase chain reaction (RT-PCR). Acute administration of MAP [4.6 mg/kg, intraperitoneally (i.p.)] increased Narp mRNA in the prefrontal cortex, whereas the same treatment with MAP decreased Narp mRNA in the hippocampus. Therefore, Narp gene could be involved in the MAP-induced effects.

[A case of Addison's disease presented with depression as a first symptom].

This report describes a 52-year-old male patient with idiopathic Addison's disease presenting depression as a first symptom. His psychomotor inhibition, depressive mood, sleep disturbances, general fatigue, muscular pain, and arthralgia were considered to be due to intense work in a stressful environment. Neither his physician nor his orthopedist found any physical disease. Therefore, he was diagnosed with endogenous depression by a psychiatric clinic, and antidepressants were prescribed. Antidepressants were not sufficient for improving his symptoms, and he was admitted to our hospital. Endocrine blood examination revealed primary adrenocortical insufficiency. Treatment with glucocorticoid induced rapid improvement in both the psychiatric and physical symptoms. It is well known that psychiatric symptoms occur in the progressive stage of Addison's disease. At present, however, the occurrence of psychiatric symptoms is very rare, mainly because of a decrease in the incidence of this disease or an increase in mild cases. In addition, Addison's disease presenting with psychiatric features in the early stage has the tendency to be overlooked and misdiagnosed. Thus, we suggest the necessity of blood work for ACTH and cortisol in the field of psychiatry.

Stress increases dynorphin immunoreactivity in limbic brain regions and dynorphin antagonism produces antidepressant-like effects.

Rats exposed to learned helplessness (LH), an animal model of depression, showed a recovery following an intracerebroventricular injection of nor-binaltorphimine dihydrochloride (norBNI; a kappa-opioid antagonist). To investigate the potential role of dynorphin A and dynorphin B, we examined the effects of different stress/depression models on dynorphin A and dynorphin B immunoreactivity in hippocampus and nucleus accumbens (NAc). Immobilization stress (3 h) caused an increase in levels of dynorphin A and dynorphin B immunoreactivity in the hippocampus and the NAc. Forced swim stress also temporally increased dynorphin A levels in the hippocampus. Furthermore, exposure to LH produced a similar increase in dynorphin A and dynorphin B in the hippocampus and NAc. Infusions of norBNI into the dentate gyrus or CA3 regions of hippocampus and into the shell or core regions of NAc produced antidepressant-like effects in the LH paradigm. The degrees of norBNI's effects were stronger in the CA3 region and NAc shell and less effective in the dentate gyrus of hippocampus and NAc core. These results indicate that both dynorphin A and dynorphin B contribute to the effects of stress, and suggest that blockade of kappa-opioid receptors may have therapeutic potential for the treatment of depression.