Arachidonic Acid Drives Postnatal Neurogenesis and Elicits a Beneficial Effect on Prepulse Inhibition, a Biological Trait of Psychiatric Illnesses

Prepulse inhibition (PPI) is a compelling endophenotype (biological markers) for mental disorders including schizophrenia. In a previous study, we identified Fabp7, a fatty acid binding protein 7 as one of the genes controlling PPI in mice and showed that this gene was associated with schizophrenia. We also demonstrated that disrupting Fabp7 dampened hippocampal neurogenesis. In this study, we examined a link between neurogenesis and PPI using different animal models and exploring the possibility of postnatal manipulation of neurogenesis affecting PPI, since gene-deficient mice show biological disturbances from prenatal stages. In parallel, we tested the potential for dietary polyunsaturated fatty acids (PUFAs), arachidonic acid (ARA) and/or docosahexaenoic acid (DHA), to promote neurogenesis and improve PPI. PUFAs are ligands for Fabp members and are abundantly expressed in neural stem/progenitor cells in the hippocampus. Our results are: (1) an independent model animal, Pax6 (+/−) rats, exhibited PPI deficits along with impaired postnatal neurogenesis; (2) methylazoxymethanol acetate (an anti-proliferative drug) elicited decreased neurogenesis even in postnatal period, and PPI defects in young adult rats (10 weeks) when the drug was given at the juvenile stage (4–5 weeks); (3) administering ARA for 4 weeks after birth promoted neurogenesis in wild type rats; (4) raising Pax6 (+/−) pups on an ARA-containing diet enhanced neurogenesis and partially improved PPI in adult animals. These results suggest the potential benefit of ARA in ameliorating PPI deficits relevant to psychiatric disorders and suggest that the effect may be correlated with augmented postnatal neurogenesis

Case report: Mitochondrial trifunctional protein deficiency caused by HADHB gene mutation (c.1175C>T) characterized by higher brain dysfunction followed by neuropathy, presented gadolinium enhancement on brain imaging in an adult patient

Mitochondrial trifunctional protein (MTP) deficiency is an autosomal recessive disorder caused by impaired metabolism of long-chain fatty acids (LCFAs). Childhood and late-onset MTP deficiency is characterized by myopathy/rhabdomyolysis and peripheral neuropathy; however, the features are unclear. A 44-year-old woman was clinically diagnosed with Charcot-Marie-Tooth disease at 3 years of age due to gait disturbance. Her activity and voluntary speech gradually decreased in her 40s. Cognitive function was evaluated and brain imaging tests were performed. The Mini-Mental State Examination and frontal assessment battery scores were 25/30 and 10/18, respectively, suggesting higher brain dysfunction. Peripheral nerve conduction studies revealed axonal impairments. Brain computed tomography showed significant calcification. Magnetic resonance imaging revealed an increased gadolinium contrast-enhanced signal in the white matter, suggesting demyelination of the central nervous system (CNS) due to LCFAs. The diagnosis of MTP deficiency was confirmed through genetic examination. Administration of L-carnitine and a medium-chain fatty triglyceride diet was initiated, and the progression of higher brain dysfunction was retarded within 1 year. This patient's presentation was suggestive of CNS demyelination. The presence of brain calcification, higher brain dysfunction, or gadolinium enhancement in the white matter in patients with peripheral neuropathy may be suggestive of MTP deficiency

A Phthalimide Derivative That Inhibits Centrosomal Clustering Is Effective on Multiple Myeloma

Despite the introduction of newly developed drugs such as lenalidomide and bortezomib, patients with multiple myeloma are still difficult to treat and have a poor prognosis. In order to find novel drugs that are effective for multiple myeloma, we tested the antitumor activity of 29 phthalimide derivatives against several multiple myeloma cell lines. Among these derivatives, 2-(2,6-diisopropylphenyl)-5-amino-1H-isoindole-1,3- dione (TC11) was found to be a potent inhibitor of tumor cell proliferation and an inducer of apoptosis via activation of caspase-3, 8 and 9. This compound also showed in vivo activity against multiple myeloma cell line KMS34 tumor xenografts in ICR/SCID mice. By means of mRNA display selection on a microfluidic chip, the target protein of TC11 was identified as nucleophosmin 1 (NPM). Binding of TC11 and NPM monomer was confirmed by surface plasmon resonance. Immunofluorescence and NPM knockdown studies in HeLa cells suggested that TC11 inhibits centrosomal clustering by inhibiting the centrosomal-regulatory function of NPM, thereby inducing multipolar mitotic cells, which undergo apoptosis. NPM may become a novel target for development of antitumor drugs active against multiple myeloma

南瓜属種間に於ける差異に関する研究 : 第四報 土壤反應が種子発芽並生育に及ぼす影響

蔬菜の生育に影響を及ぼす環境要素の中で, 土壤反應と云ふ事は見遁す事の出來ない要素であり, 多くの学者に依り種々の作物により実驗報告されてゐるが, 今日迄南瓜属に係る此の様な実驗は見ないのである。故に筆者は種間の差違を調査檢討する目的と, 現在迄に施行された植物生育と土壤酸度との関係を調査するに当り, 土壤酸度により種子発芽に影響があり其の後の生育にも相当の影響を與へる事を考慮しないで論ずるのは無理と云ふ考へのもとに, 先づ発芽適温を調べ, 酸度の差違が発芽に及ぼす影響, 土壤反應が生育に及ぼす影響の差違を檢し, 土壤反應と葉部組織酸度との関係を調査し生育に於ける土壤反應の限界点を試べたものである。結果I. [table] II. 種間に於ける植物体葉部組織酸度の相違は極めて少いが, 土壤反應がアルカリ性(酸性)になるにともなひ, 植物体内の酸度もアルカリ性(酸性)を呈する。Among many environmental elements which act upon the growth of vegetables, the soil reaction would be the factor not to be disregarded. And so the investigators have conducted experiments on various crops and have given reports of them. But we have not found yet such an experiment of Cucurbita species. Now, if we are to investigate and argue on the intraspecific differences of Cucurbita, and relations between the growth of plant and soil acidity, hither explained, we arrive at the conclusion as follows Results I. [table] II. The intraspeciffc difference between the leave\u27s pH is quite insignificant, but keeping pace with alkarine (acidic) of the soil reaction, the acidity in the plant body itself also shows alkarine (acidic)

第八報 気孔並花粉粒の種間的差異(南瓜属に於ける形態学的差異に関する研究)

1. 本実験は第3報告の続きとして, 気孔並花粉粒の種間的差異を調査した。2. 気孔は3種とも形は略同様であるが, 大さ及一定面積内の数に於ては maxima Pepo, moschata と云う順位を示す。3. 気孔の数及大さが栽培過程に於ける露菌病罹病の多少に影響を及す。4. 花粉粒は種間に於て明確に差異を生ずる。色は maxima 種のみ稍黄緑色を呈するが他の2種は黄色を呈する。(之は種間に於ける花瓣の色と同様の傾向を示す)花粉粒の大さ及突起の大さは moschata 種, Pepo 種, maxima 種の順位を示す。5. 花粉粒はオシロイ花と共に最も大きい方に属する。(112∿148μ) 6. 花粉粒の種間的差異により種の分類が可能である。1. This experiment follows the report III in the examination of the interspecific differences of stomata and pollen. 2. The three species are similar in shape of stomata, but the gradation in size and number of stomata is as follows : i) maxima ii) Pepo iii) moschata 3. In the process of cultivation the rate of incidence of Pseudoperonospora is influenced by the size and number of stomata. 4. Their pollons as well as those of Mirabillis, are the biggest of their kind (112∿148μ). 5. Pollens have an apparent interspecific differences. Those of maxima are pale yellow-green while those of the other two species are yellow. (The same inclination is to be found in the color of petals.) The gradation in the size of pollens and protuberances is as follows : i) moschata ii) Pepo iii) maxima 6. The classification of those species is made possible by the interspecific differences of their pollens