Maternal Immune Activation Affects Hippocampal Excitatory and Inhibitory Synaptic Transmission in Offspring From an Early Developmental Period to Adulthood.

One of the risk factors for schizophrenia is maternal infection. We have previously shown that Polyriboinosinic-polyribocytidylic acid (poly I:C) induced maternal immune activation in mice caused histological changes in the hippocampal CA1 area of offspring during the developmental period and impaired sensorimotor gating in offspring during adulthood, resulting in behavioral changes. However, it remains unclear how maternal immune activation functionally impacts the hippocampal neuronal activity of offspring. We studied the effect of prenatal poly I:C treatment on synaptic transmission of hippocampal CA1 pyramidal cells in postnatal and adult offspring. Treatment with poly I:C diminished excitatory and enhanced inhibitory (GABAergic) synaptic transmission on pyramidal cells in adult offspring. During the early developmental period, we still observed that treatment with poly I:C decreased excitatory synaptic transmission and potentially increased GABAergic synaptic transmission, which was uncovered under a condition of high extracellular potassium-activated neurons. In conclusion, we demonstrate that maternal immune activation decreased excitatory and increased inhibitory synaptic transmission on hippocampal pyramidal cells from an early developmental period to adulthood, which could result in net inhibition in conjunction with poor functional organization and integration of hippocampal circuits.

Tai Chi exercise versus rehabilitation for the elderly with cerebral vascular disorder: a single-blinded randomized controlled trial.

BACKGROUND: Cerebral vascular disorder (CVD) might result in a quantifiable decrease in quality of life, which is determined not only by the neurological deficits but also by impairment of cognitive functions. There are few studies that report on the cognitive effect of Tai Chi exercise (Tai Chi) on the elderly with CVD. The purpose of the present study was to examine the cognitive effect of Tai Chi on the elderly with CVD using P300 measurement, in addition to the General Health Questionnaire (GHQ) and Pittsburgh Sleep Quality Index (PSQI). METHODS: A total of 34 patients with CVD were recruited from outpatient Akistu-Kounoike Hospital and randomly assigned to receive Tai Chi (n= 17) or rehabilitation (n= 17) in group sessions once a week for 12 weeks. To examine the time courses of each score (P300 amplitude, P300 latency, GHQ score and PSQI score), repeated-measures analysis of variance was carried out with groups and time as factors. RESULTS: For the time courses of P300 amplitudes and latencies, there were no significant effects of interaction between group and time. However, significant time-by-group interactions were found for Sleep Quality (P= 0.006), GHQ total score (P= 0.005), anxiety/insomnia score (P= 0.034), and severe depression score (P= 0.020). CONCLUSIONS: Tai Chi might therefore be considered a useful non-pharmacological approach, along with rehabilitation, for the maintenance of cognitive function in the elderly with CVD and might be a more useful non-pharmacological approach for the improvement of sleep quality and depressive symptoms in the elderly with CVD than rehabilitation.

Yi-gan san restores behavioral alterations and a decrease of brain glutathione level in a mouse model of schizophrenia.

The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.

Type d syndrome of inappropriate antidiuretic hormone secretion in a schizophrenia patient with polydipsia.

A 55-year-old man with schizophrenia developed water intoxication due to primary polydipsia. His manner of antidiuretic hormone secretion was investigated by water loading and infusion of hypertonic saline to clarify the form of the syndrome of inappropriate antidiuretic hormone secretion. The plasma antidiuretic hormone level, which may be involved in the occurrence of water intoxication, was consistently low in this patient, and linked to type D syndrome of inappropriate antidiuretic hormone secretion, designated "hypovasopressinemic antidiuresis". Although this type is not common, it should be considered as a pathophysiology for water intoxication in schizophrenia patients.

Lysophosphatidylcholine induces delayed myelination in the juvenile ventral hippocampus and behavioral alterations in adulthood.

Maternal virus infection or maternal polyinosinic-polycytidilic acid injection confers behavioral alterations including deficit in prepulse inhibition on the offspring. We previously found delayed myelination specifically in the early postnatal hippocampus in the polyinosinic-polycytidilic acid-injection model. To test whether the transient delay in myelination in the juvenile hippocampus leads to abnormal behaviors after adolescence, we injected lysophosphatidylcholine, a potent demyelinating agent, into the ventral hippocampus of the 10-day-old rat. The lysophosphatidylcholine treatment yielded hypomyelination at postnatal day 16, but myelination reverted to normal level in the adult rat. Neuronal arrays and morphology were not disturbed in this model. We then performed a battery of behavioral tests on the lysophosphatidylcholine-treated and control PBS-injected rats. The lysophosphatidylcholine-treated rats showed deficit in prepulse inhibition, motor hyperactivity in response to methamphetamine and anxiety-related behaviors, all of which are typical behaviors observed in the maternal infection models. These findings suggest that the timing of myelination in the early postnatal hippocampus is crucial for the proper development of sensorimotor and emotional functions. The lysophosphatidylcholine-treated rat without a gross anatomical defect is useful as a model for psychotic disorders.

Maternal immune activation in mice delays myelination and axonal development in the hippocampus of the offspring.

Epidemiological data suggest a relationship between maternal infection and a high incidence of schizophrenia in offspring. An animal model based on this hypothesis was made by injecting double-stranded RNA, polyinosinic-polycytidylic acid (poly-I:C), into early pregnant mice, and their offspring were examined for biochemical and histological abnormalities. Mouse brains were examined with special reference to oligodendrocytes, which have been implicated in several neurodevelopmental disorders. We detected a significant decrease of myelin basic protein (MBP) mRNA and protein at early postnatal periods in poly-I:C mice. MBP immunocytochemistry and electron microscopy revealed that the hippocampus of juvenile poly-I:C mice was less myelinated than in PBS mice, with no significant loss of oligodendrocytes. In addition, axonal diameters were significantly smaller in juvenile poly-I:C mice than in control mice. These abnormalities reverted to normal levels when the animals reached the adult stage. These findings suggest that retarded myelination and axonal abnormalities in early postnatal stages caused by maternal immune activation could be related to schizophrenia-related behaviors in adulthood.

Chemical preconditioning prevents paradoxical increase in glutamate release during ischemia by activating ATP-dependent potassium channels in gerbil hippocampus.

Ischemic tolerance induced by pretreatment with a low dose of 3-nitropropionic acid (3-NPA), called chemical preconditioning, prolongs the delay to hypoxic depolarization and improves the recovery of synaptic transmission (Exp. Neurol. 166 (2000), 385-391). We studied the effect of chemical preconditioning on the presynaptic site by analyzing spontaneous excitatory postsynaptic currents (sEPSCs) and miniature EPSCs (mEPSCs) with a whole cell patch-clamp technique in gerbil hippocampal slices. The frequency of sEPSCs decreased first and then dramatically increased during ischemia (10 min in duration, low pO(2), and deprivation of glucose) up to 200-300%. This increase was apparently a paradox, since synaptic transmission evoked by electrical stimulation diminished when the sEPSC frequency started to increase. The frequency of mEPSCs also increased in the same time course. Increases in sEPSC and mEPSC frequencies were prevented by chemical preconditioning with 3-NPA (4 mg/kg) administered intraperitoneally 3 h before the preparation of brain slices. These effects of chemical preconditioning were abolished by glibenclamide (5 microM), a blocker of ATP-dependent potassium (K(ATP)) channels, applied in vitro before the ischemic insult. The application of diazoxide (500 microM), an opener of K(ATP) channels, produced the same preventive effects on sEPSC and mEPSC frequencies. These results suggested that chemical preconditioning acted on presynaptic terminals to prevent the paradoxical increase in glutamate release during ischemia through the activation of K(ATP) channels.