Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia.

BACKGROUND: Maternal viral infection is associated with increased risk for schizophrenia. It is hypothesized that the maternal immune response to viruses may influence fetal brain development and lead to schizophrenia. METHODS: To mimic a viral infection, the synthetic double strand RNA polyriboinosinic-polyribocytidilic acid (poly I:C) was administered into pregnant mice. Behavioral evaluations (thigmotaxis, methamphetamine [MAP]-induced hyperactivity, novel-object recognition test [NORT]), sensorimotor gating (prepulse inhibition [PPI]), and biochemical evaluation of the dopaminergic function of the offspring of phosphate-buffered saline (PBS)-treated dams (PBS-mice) and that of poly I:C-treated dams (poly I:C-mice) were examined. RESULTS: In juveniles, no difference was found between the poly I:C-mice and PBS-mice. However, in adults, the poly I:C-mice exhibited attenuated thigmotaxis, greater response in MAP-induced (2 mg/kg) hyperlocomotion, deficits in PPI, and cognitive impairment in NORT compared with the PBS-mice. Cognitive impairment in the adult poly I:C-mice could be improved by subchronic administration of clozapine (5.0 mg/kg) but not haloperidol (.1 mg/kg). Increased dopamine (DA) turnover and decreased receptor binding of D2-like receptors, but not D1-like receptors, in the striatum were found in adult poly I:C-mice. CONCLUSIONS: Prenatal poly I:C administration causes maturation-dependent increased subcortical DA function and cognitive impairment in the offspring, indicating a neurodevelopmental animal model of schizophrenia.     

Dopamine transporter imaging with novel, selective cocaine analogs.

RTI-121 and RTI-122 are 3 beta-substituted phenyltropane analogs of cocaine that have high, selective binding affinity for dopamine transporters. [123I]RTI-121 and [123I]RTI-122 bind to dopamine transporters in vivo after intravenous administration and permit imaging of the transporters.     

11C-glucose metabolism in manic and depressed patients

The authors used positron emission tomography (PET) and 11C-labeled glucose to study 15 unmedicated patients with affective disorders and 7 control subjects. Diagnoses of affective disorders were based on DSM-III criteria, and symptomatology was evaluated by the Hamilton Rating Scale for Depression. Blood counts of 11C in both unipolar and bipolar patients did not differ from those in controls after oral administration of 11C-glucose. By contrast, brain counts of 11C in unipolar depressed patients were significantly lower, whereas those in bipolar manic patients were significantly higher, than in normal controls.     

Iron deposition in the brain of a case of the special type of hepatocerebral encephalopathy

The histochemical demonstration of iron and the iron content was examined in the brain of a case of the special type of hepatocerebral encephalopathy (HCE). The patient had suffered from a liver disease since 36 years old. At 44 years old, she experienced the first attack of twilight state with flapping tremor. She had predilection for eating beans. Her personality gradually became euphoric with the recurrent episodes of unconsciousness. At 54 years old, she died of the complication of melena, renal insufficiency and pneumonia. The liver showed cirrhotic changes and iron content of liver was 0 or 1 after MacDonald's criterion scale. The histopathological findings of the brain showed the characteristic changes of HCE, which were incomplete softening and spongy state pseudolaminarilly extending in the deep layer of the cerebral cortex, the proliferation of the severely changed Alzheimer 2 type glia with or without intranuclear carmine positive substance. The deparaffinized sections, 20 mu in thickness, which were not fastened on slides were used for the histochemical study of iron, because iron deposits displaced inside of the brain tissues when the paraffin sections were fastened on slide glasses in the constant-temperature bath. The iron deposition was found in the central gyrus, superior temporal gyrus, medial and lateral occipito-temporal gyrus and middle temporal gyrus of occipital lobe. The iron accumulated in the ground substance, glia cell bodies, glia nuclei and unknown bodies in the 3-6 layers of cerebral cortex of these gyri. The iron accumulation demonstrated histochemically in other parts of the brain were group 1, 2 by Spatz, mammillary body, glia cell bodies in cerebellar white matter and pons.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gerstmann-Sträussler syndrome — A variant type: amyloid plaques and Alzheimer's neurofibrillary tangles in cerebral cortex

Summary This report presents a variant of Gerstmann-Sträussler syndrome (GSS). A 53-year-old female had developed slowly progressive dementia and atactic gait since the age of 45. No myoclonic jerks and periodic synchronous discharges were observed throughout the illness. The neuropathological study revealed that many amyloid plaques and widespread Alzheimer's neurofibrillary tangles (NFTs) appeared in the cerebral cortex. Characteristically, the plaques reacted with anti-prion protein and none of them reacted with anti- protein, and they were made of many components, including amyloid cores, macrophages laden with lipid granules and/or degenerated neurites. Neuropil threads were seen mainly in amyloid plaques. Moreover, plaques appeared which were confluent and laminar in arrangement in the fifth and sixth cortical layers and had a close relationship to the neuronal loss. There was no spongiform change in the cerebral cortex or cerebellum. The cerebellum was almost intact except for a few amyloid plaques. Ultrastructurally, some of the plaques simulated kuru plaques and others had many degenerated neurites possessing paired helical filaments and other accumulated organelles. GSS has been proposed to include cases with progressive ataxia, dementia and massive multifocal plaques in the brain with or without cerebral spongiform changes. The case presented here is a very peculiar case of GSS. Recently, similar cases have been reported in some large families, diagnosed as familial Alzheimer's disease. These cases may be a telencephalic form with numerous NFTs of GSS.