Spongy Degeneration Research Articles

Neuropathology of mitochondrial diseases

The term "mitochondrial diseases" (MD) refers to a group of disorders related to respiratory chain dysfunction. Clinical features are usually extremely heterogeneous because MD may involve several tissues with different degrees of severity. Muscle and brain are mostly affected, probably because of their high dependence on oxidative metabolism. Muscle can be the only affected tissue or involved as a part of a multi-system disease; ragged red fibers, accumulation of structurally altered mitochondria and cytochrome-c-oxidase (COX) negative fibers are the main pathological features. In mitochondrial encephalopathies, central nervous system (CNS) structures are affected according to different patterns of distribution and severity. Characteristic lesions are neuronal loss, vasculo-necrotic changes, gliosis, demyelination and spongy degeneration. In accordance with either grey matter or white matter involvement two main groups of diseases may be distinguished. Neuronal loss and vasculo-necrotic multifocal lesions are the common features of grey matter involvement; demyelination and spongy degeneration occur when white matter is affected, often associated with less severe lesions of the grey structures. Grey matter lesions are prevalent in MERRF, MELAS, Alpers and Leigh syndromes. White matter involvement is always seen in Kearns-Sayre syndrome and was recently described in mtDNA depletion syndrome linked to dGK mutations and in the rare conditions associated with complex I and II deficiency. In this review we describe the main histopathological features of muscle and CNS lesions in mitochondrial diseases.

N-Acetylaspartic acid promotes oxidative stress in cerebral cortex of rats

N-Acetylaspartic acid accumulates in Canavan Disease, a severe leukodystrophy characterized by swelling and spongy degeneration of the white matter of the brain. This inherited metabolic disease, caused by deficiency of the enzyme aspartoacylase, is clinically characterized by severe mental retardation, hypotonia and macrocephaly, and also generalized tonic and clonic type seizures in about half of the patients. Considering that the mechanisms of brain damage in this disease remain not fully understood, in the present study we investigated whether oxidative stress is elicited by N-acetylaspartic acid. The in vitro effect of N-acetylaspartic acid (10–80mM) was studied on oxidative stress parameters: total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR), chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), reduced glutathione content, sufhydryl content and carbonyl content in the cerebral cortex of 14-day-old rats. The effect of the acute administration of N-acetylaspartic acid (0.1–0.6mmol/g body weight) was studied on TRAP, TAR, carbonyl content, chemiluminescence and TBA-RS. TRAP, TAR, reduced glutathione content and sulfhydryl content were significantly reduced, while chemiluminescence, TBA-RS and carbonyl content were significantly enhanced by N-acetylaspartic acid in vitro. The enhancement in TBA-RS promoted by N-acetylaspartic acid was completely prevented by ascorbic acid plus Trolox, and partially prevented by glutathione and dithiothreitol. The acute administration of N-acetylaspartic acid also significantly reduced TRAP and TAR, and significantly enhanced carbonyl content, chemiluminescence and TBA-RS. Our results indicate that N-acetylaspartic acid promotes oxidative stress by stimulating lipid peroxidation, protein oxidation and by decreasing non-enzymatic antioxidant defenses in rat brain. This could be another pathophysiological mechanism involved in Canavan Disease.

La maladie de Canavan ou acidurie N-acétyl aspartique : à propos de 1 cas

Canavan disease or N-acetyl aspartic aciduria, is an autosomal recessive leukodystrophy characterized by spongy degeneration of brain. The disease is an inborn error of metabolism caused by aspartoacylase deficiency resulting from accumulation of N-acetyl aspartic acid in the brain. The authors report a case in a 10-month-old boy who presented with developmental delay and megalencephaly noticeable after 4 months of age. Magnetic resonance imaging of the brain showed diffuse white matter degeneration. The diagnosis of Canavan disease was confirmed by nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry.

Chronic cardiomyopathy and encephalic spongy changes in sheep experimentally fed Ateleia glazioviana

Fifteen mature crossbred sheep were fed different daily amounts (2.5-35g kg-1 bw) of the fresh green leaves of Ateleia glazioviana for different periods of time (1-24 days). One sheep was not fed the plant and served as a control. All 16 sheep were euthanatized at different stages of the experiment, necropsied, and several organs, including heart and brain were evaluated histologically. Samples of five brain regions from three affected sheep were evaluated by electron microscopy. Clinical signs observed in three sheep included depression, anorexia, general weakness, staggering gait and prolonged recumbency. One sheep had signs of congestive heart failure. Necropsy findings included subcutaneous dependent edema and edema of the body cavities in two sheep and nutmeg liver in one. Histopathological findings included degeneration, necrosis and interstitial fibrosis in the myocardium of four sheep and vacuolation of cerebral white matter (spongy degeneration, status spongiosus) in 10 sheep, although this latter change were marked only in two of those 10. The ultrastructure of the brain lesion was morphologically consistent with that found in diseases grouped as spongiform myelinopathies in which vacuolation of the myelin occurs in the absence of significant myelin breakdown or phagocytosis. The morphology and pathogenesis of the chronic cardiomyopathy and of the cerebral spongy degeneration in affected sheep in this experiment are discussed and compared with other similar conditions in domestic ruminants.

Expression of Iba1 protein in microglial cells of zitter mutant rat

Microglial activation has been associated with the pathogenesis of neurodegenerative disease. To characterize microglial responses in the zitter mutant rat, which shows progressive spongy degeneration, the development of microglial cells was investigated using ionized calcium-binding adaptor molecule (Iba1) antibody as a specific marker of microglial cells. Neurochemical analysis showed transiently increased Iba1 protein levels in the brains of developing Sprague–Dawley (SD) rats. However, high Iba1 protein readings continued in aged zitter rats. Immunohistochemical analysis revealed time-course differences in the transformation of microglia between SD and zitter rats and prolonged activation of microglial cells in the zitter rat. In the zitter rat, activated microglial cells characterized by swollen cell bodies and shorter, thicker processes were distributed throughout the brain from 2-weeks- to 2-months-old. After 2-months-old, numbers of activated microglial cells gradually decreased. However, these cells were not observed in SD rats. Iba1-immunoreactive cell-clusters organized by at least five activated microglial cells were also prominent in the zitter brain. These differences reflect the neuropathology of this mutant rat triggered by deletion of the attractin gene. The present data may thus suggest that microglial cells directly or indirectly contribute to progressive spongy degeneration in zitter mutant rats.

Mice with mutations in Mahogunin ring finger‐1 (Mgrn1) exhibit abnormal patterning of the left–right axis

Mahogunin Ring Finger 1 (Mgrn1) encodes a RING-containing protein with ubiquitin ligase activity that has been implicated in pigment-type switching. In addition to having dark fur, mice lacking MGRN1 develop adult-onset spongy degeneration of the central nervous system and have reduced embryonic viability. Observation of complete situs inversus in a small proportion of adult Mgrn1 mutant mice suggested that embryonic lethality resulted from congenital heart defects due to defective establishment and/or maintenance of the left-right (LR) axis. Here we report that Mgrn1 is expressed in a pattern consistent with a role in LR patterning during early development and that many Mgrn1 mutant embryos show abnormal expression of asymmetrically expressed genes involved in LR patterning. A range of complex heart defects was observed in 20-25% of mid-to-late gestation Mgrn1 mutant embryos and another 20% were dead. This finding was consistent with 46-60% mortality of mutants by weaning age. Our results indicate that Mgrn1 acts early in the LR signaling cascade and is likely to provide new insight into this developmental process as Nodal expression was uncoupled from expression of other Nodal-responsive genes in Mgrn1 mutant embryos. Our work identifies a novel role for MGRN1 in embryonic patterning and suggests that the ubiquitination of MGRN1 target genes is essential for the proper establishment and/or maintenance of the LR axis.

Intoxicação de bovinos por Tetrapterys multiglandulosa (Malpighiaceae) em Mato Grosso do Sul

São descritos dois surtos da intoxicação espontânea por Tetrapterys multiglandulosa em bovinos e a reprodução experimental da toxicose em ovinos. Os dois surtos espontâneos ocorreram na mesma fazenda localizada no município de Bataiporã, Mato Grosso do Sul. O primeiro surto ocorreu em julho-outubro de 2004 e envolveu uma população bovina sob risco de 290 vacas prenhes que haviam sido introduzidas em um pasto de 60 hectares onde havia uma área de reserva legal, altamente infestada por T. multiglandulosa. Dessas, 230 vacas (79,3%) abortaram, pariram natimortos ou bezerros fracos que morreram alguns dias após o nascimento. Sete vacas adultas morreram. Uma vaca e um bezerro de 10 dias foram necropsiados. O segundo surto ocorreu em setembro-outubro de 2005, 40 dias após 285 novilhas de dois anos de idade terem sido introduzidas no mesmo pasto infestado por T. multiglandulosa onde ocorrera o primeiro surto no ano anterior. Nove novilhas adoeceram e morreram; três foram necropsiadas. Os sinais clínicos dos bovinos afetados, incluindo um bezerro de 10 dias de idade, consistiam de acentuada letargia, emagrecimento com distensão do abdômen (ascite), edema subcutâneo de declive, ingurgitamento e pulso venoso da jugular, dispnéia e arritmia cardíaca. Os achados de necropsia incluíam corações globosos e com câmaras cardíacas dilatadas, áreas brancas e firmes no miocárdio e alterações relacionadas a insuficiência cardíaca como edemas cavitários, fígado de noz-moscada, edema pulmonar e grande coágulo no ventrículo esquerdo. As alterações histopatológicas incluíam necrose e fibrose do miocárdio, congestão centrolobular passiva crônica do fígado, edema pulmonar e degeneração esponjosa da substância branca do encéfalo. Os ovinos do experimento morreram 29 (Ovino 1) e 35 (Ovino 2) dias após terem recebido as folhas de T. multiglandulosa nas doses médias diárias de 14 g/kg (Ovino 1) e 7,5 g/kg (Ovino 2). O aparecimento dos sinais clínicos ocorreu a partir do 7º dia (Ovino 1) e do 4º dia (Ovino 2) de experimento e incluíam taquicardia e arritmia, letargia e pressão da cabeça contra objetos. Os achados de necropsia e histopatologia em ambos os ovinos experimentais foram estreitamente semelhantes aos observados nos bovinos afetados nos dois surtos espontâneos.

Degeneração esponjosa no sistema nervoso central de bezerros da raça Sindhi

Degeneração esponjosa (status spongiosus) agrupa várias alterações histológicas caracterizadas pela formação de vacúolos no neurópilo em diferentes regiões do sistema nervoso central (SNC). Essa vacuolização pode ser por edema intramielínico, como na doença da urina com odor de xarope de bordo (maple syrup urine disease) e algumas doenças tóxicas, ou por edema de astrócitos, como na citrulinemia. Este trabalho descreve degeneração esponjosa do SNC em dois bezerros, um macho e uma fêmea, da raça Sindhi. Ambos são filhos de um mesmo touro, de um rebanho que apresentava alto grau de consangüinidade. Uma fêmea nasceu normal e aos 2 meses apresentou sinais nervosos progressivos. Um macho apresentou sinais nervosos progressivos desde o nascimento. Os dois foram eutanasiados aos 4 meses de idade com acentuadas alterações do sistema nervoso central. Na necropsia o fígado de bezerro macho estava pálido. Histologicamente havia, em ambos os bezerros, discreta a acentuada vacuolização difusa do SNC, sendo mais acentuada nas camadas profundas do córtex cerebral, cápsula interna, substância branca da medula cerebelar, tronco encefálico e substância cinzenta da medula. No fígado dos dois animais havia degeneração gordurosa nos hepatócitos da região centrolobular. Na microscopia eletrônica observou-se que o status spongiosus era devido a edema astrocitário. Sugere-se que a doença é causada por um erro metabólico hereditário, diferente da doença da urina com odor de xarope de bordo.

Effect of Dietary Restriction on Learning and Memory Impairment and Histologic Alterations of Brain Stem in Senescence‐Accelerated Mouse (SAM) P8 Strain

The age-associated spontaneous spongy degeneration in the brain stem of senescence-accelerated mouse (SAM) P8 strain has been suggested to be closely associated with the ability to learn and memorize. In this study, we investigated the effects of dietary restriction (DR) initiated from weaning on learning and memory and histologic changes of the brain stem in P8 and control R1 mice. Although no effect of DR was observed in the retention of the passive-avoidance response in both the P8 and R1 mice, the acquisition of the task was significantly improved by DR in P8 mice. On the other hand, the total area and number of vacuoles in the brain stem was significantly higher in ad libitum-fed (AD)-P8 mice than in AD-R1 mice. However, no significant effect was observed on the vacuole formation in the brain stem of P8 mice by DR. These observations suggest that the improvement of the acquisition of the task by DR in P8 mice is possibly due to changes in neuronal function rather than histologic alteration in brain stem.

Favorable Effects of Tea on Reducing the Cognitive Deficits and Brain Morphological Changes in Senescence-Accelerated Mice

The present study was carried out to explore the effects of oolong and green teas on improving the memory deficits and brain pathological changes in senescence accelerated-prone mice P8 (SAMP8). Six-month-old mice were supplied with oolong tea, green tea or water as the sole drinking fluid for 16 wk. The memory ability of mice was evaluated by passive and active avoidance tests, while the extent of the brain degeneration was measured by the spongiosis grades and the lipofuscin percentage in the hippocampus. The total grading score and serum biochemical levels were also measured. The results indicated that the mice supplemented with the oolong and green tea drinks reversed the cognitive impairment, lessened the spongy degeneration and lipofuscin, and increased the serum Trolox equivalent antioxidant capacity more than the control group. The total grading score of the oolong tea group was lower than that of the control group in male mice, whereas it did not differ among female groups. No differentiations in the concentrations of total cholesterol. triglyceride, glucose, iron or hemoglobin were observed among three drink groups. In conclusion, oolong and green teas could reduce the deteriorations of cognitive ability, brain degenerative changes and aging process in SAMP8, probably through the potent antioxidative activity of the tea.

Application of ultrasonic examination by color Doppler's method in portal vein disease

目的 探讨彩色多普勒对门静脉疾病的诊断价值.方法将28例门静脉疾病患者行彩色多普勒超声检查并行手术及造影证实.结果 28例中确诊17例为门静脉血栓,5例为门静脉内癌栓,1例胰腺炎,2例假性胰腺囊肿,2例为先天性门静脉发育畸形,1例门静脉血管癌.结论彩色多普勒能确诊门静脉疾患。

Aspartoacylase gene knockout results in severe vacuolation in the white matter and gray matter of the spinal cord in the mouse

Canavan disease (CD) is a neurodegenerative disorder characterized by the spongy degeneration of the white matter of the brain. Aspartoacylase (ASPA) gene mutation resulting enzyme deficiency is the basic cause of CD. Whether the ASPA defect in CD affects the spinal cord has been investigated using the ASPA gene knockout mouse. Luxol fast blue-hematoxylin and eosin staining in the spinal cord of the knockout mouse showed vacuolation in both white matter and gray matter areas of cervical, thoracic, lumbar, and sacral segments of the spinal cord. However, more vacuoles were seen in the gray matter than the white matter of the spinal cord. ASPA activity in the cervical, thoracic, lumbar, and sacrococcygeal regions of the spinal cord was significantly lower in the knockout mouse compared to the wild type. The enzyme defect in the knockout mouse was also confirmed using the Western blot method. These observations suggest that the ASPA gene defect in the mouse leads to spinal cord pathology, and that these changes may be partly involved in the cause of the physiological/behavioral abnormalities seen in the knockout mouse, if documented also in patients with CD.

A Neurological Disease with Spongy Degeneration in a Newborn Japanese Black Calf

A Japanese Black calf, 3 day-old male, showed severe ataxia, lateral recumbency, and opisthotonos at the birth. Histopathological examinations revealed severe status spongiosis throughout the central nervous system. Numerous vacuoles within the neuropile varying in size and shape were observed in both formalin-fixed paraffin and cryostat sections. In the lesions, a limited number of spheroids and macrophages were observed within the myelin sheaths with very mild astrogliosis. These vacuoles were negative for both periodic acid Schiff and Sudan black stains. The clinical and histopathological features were almost in conformity with those of bovine maple syrup urine disease (MSUD). Although we could not confirm completely the etiology, congenital hereditary neurological diseases including MSUD are considerable as the possible disease entry in the present case.

Aspectos epidemiológicos da seneciose na região sul do Rio Grande do Sul

Seneciose é a principal intoxicação por planta no sul do Rio Grande do Sul, Brasil. Neste trabalho apresentam-se os dados de 24 surtos de seneciose em bovinos e de um em eqüinos, diagnosticados pelo Laboratório Regional de Diagnóstico (LRD) da Universidade Federal de Pelotas, no período de 1998 a 2000. Adicionalmente são avaliados os dados epidemiológicos de 54 surtos ocorridos no período 1978-1997. Os dados epidemiológicos e clínicos do período 1998-2000 foram coletados em visitas às propriedades onde estavam ocorrendo os surtos. Em 11 (45,83%) surtos os animais tinham até 3 anos de idade e, em 13 (54,16%), 3 anos ou mais. Quanto ao sexo, 9 (37,5%) surtos atingiram fêmeas e 15 (62,5%) afetaram machos. Em relação à época de ocorrência, 10 (41,66%) surtos ocorreram na primavera, 4 (16,66%) no verão, 5 (20,83%) no outono, e 5 (20,83%) no inverno. A morbidade foi estimada em 4,92% e a letalidade em 95,59%. As espécies de Senecio que predominaram nas propriedades visitadas foram S. brasiliensis em 12 (57,14%), S. selloi em 10 (47,61%), S. oxyphyllus em 6 (28,57%), S. heterotrichius em 3 (14,28%), e S. leptolobus em 1 (4,76%) propriedade. Os sinais clínicos mais freqüentes foram emagrecimento progressivo, incoordenação, diarréia, tenesmo, prolapso retal e agressividade. O curso clínico da intoxicação, levando em consideração somente os animais necropsiados ou os observados durante as visitas às fazendas, foi de 24 a 96 horas em 4 (16,66%) surtos, de 4 a 7 dias em 7 (29,16%), de 1 a 2 semanas em 4 (16,66%), de 2 a 3 semanas em 2 (8,33%), de 1 a 2 meses em 2 (8,33%), e de 2 a 3 meses em 1 (4,16%) surto. Em quatro (16,66%) surtos o período de manifestação clínica não foi observado. Nos surtos em que o curso clínico foi mais prolongado, alguns animais apresentaram fotossensibilização. Os achados de necropsia mais comuns foram fígado aumentado de tamanho e endurecido, vesícula biliar aumentada, edema no mesentério e abomaso e líquido nas cavidades. No fígado, a histopatologia revelou fibroplasia, megalocitose e proliferação de células dos ductos biliares e, no cérebro, degeneração da substância branca. Em amostras das diferentes espécies de Senecio, coletadas em diferentes épocas do ano, foi determinada a concentração de alcalóides pirrolizidínicos (APs) e seus N-óxidos através de cromatografia de camada delgada e espectrofotometria. Retrorsina foi encontrada em Senecio brasiliensis, S. heterotrichius, S. selloi e S. oxyphyllus. Além deste, S. brasiliensis e S. heterotrichius registraram mais um e dois alcalóides não identificados, respectivamente. A maior concentração de AP reduzido (AP livre + N-óxido) foi encontrada em S. brasiliensis no inverno (0,25%). Nessa mesma época quantidades decrescentes de AP reduzidos foram encontradas em S. heterotrichius (0,19%), S. oxyphyllus (0,03%) e S. selloi (0,03%). Em S. leptolobus não foram detectados alcalóides. Esses dados demonstraram que S. brasiliensis é a espécie mais importante como causa de seneciose no sul do Rio Grande do Sul. Adicionalmente, foram analisados dados de arquivo do LRD sobre 54 surtos de intoxicação por AP no período 1978-1997. Nesse período, 7 (12,96%) surtos afetaram bovinos menores de 3 anos, 39 (72,22%) afetaram bovinos de 3 anos ou mais, 3 (5,55%) afetaram bovinos de várias idades e, em 5 (9,25%) surtos a idade não foi informada. Trinta e nove (72,22%) surtos afetaram fêmeas, 7 (12,96%) afetaram machos, 3 (5,55%) afetaram ambos os sexos e, em 5 (9,25%), o sexo não foi informado. Vinte e três (42,59%) surtos ocorreram na primavera, 9 (16,66%) no verão, 9 (16,66%) no outono, e 13 (24,07%) no inverno. O maior número de surtos da intoxicação no período 1998-2000 (24 surtos em 3 anos) em relação ao período 1978-1997 (54 surtos em 20 anos) pode estar relacionado à diminuição em mais de 50% da população ovina no Estado.

Staging of argyrophilic grains: an age-associated tauopathy.

We have reported that the ambient gyrus is the site with the greatest accumulation of argyrophilic grains (AGs) and that the degeneration of the ambient gyrus is responsible for dementia with grains. Here we analyzed 1,405 serial autopsy cases from 2 hospitals and detected AGs only in cases older than 56 years of age. The distribution of AGs followed a stereotypic regional pattern. Thus, we propose the following staging paradigm: stage I: AGs restricted to the ambient gyrus and its vicinity; stage II: AGs more apparent in the anterior and posterior medial temporal lobe, including the temporal pole, as well as the subiculum and entorhinal cortex; and stage III: abundant AGs in the septum, insular cortex, and anterior cingulate gyrus, accompanying spongy degeneration of the ambient gyrus. Sixty-three of 65 (96.9%) argyrophilic grain stage III cases without other dementing pathology were classified as 0.5 or higher in the clinical dementia rating. Forty-seven of 50 dementia with grains cases (94%) were stage III and 3 were stage II. No association with apoE genotyping was detected. Our study further confirms that dementia with grains is an age-associated tauopathy with relatively uniform distribution and may independently contribute to cognitive decline in the elderly.

Mouse neural progenitor cells differentiate into oligodendrocytes in the brain of a knockout mouse model of Canavan disease

Canavan disease (CD) is an autosomal recessive disorder that leads to spongy degeneration in the white matter of the brain. Aspartoacylase (ASPA) synthesizing cells, oligodendrocytes, are lost in CD. Transplantation of neural progenitor cells (NPCs) offers an interesting therapeutic approach for treating neurodegenerative diseases by replacing the lost cells. Therefore, the NPCs transplantation to the brain of the CD mouse was studied. Injection of mouse NPCs to the striatum and cerebellum of juvenile CD mouse showed numerous BrdU positive cells at 1 month after injection. The same result was also observed in the adult CD mouse brain after 5 weeks of post-transplantation period. The implanted cells differentiated into oligodendrocytes and fibrous astrocytes, as observed using glial cell marker. This is the first report to describe the survival, distribution and differentiation of NPCs within the brain of CD mouse and a first step toward the potential clinical use of cell therapy to treat CD.

Protection against malonate-induced ischemic brain injury in rat by a cell-permeable peptidic c-Jun N-terminal kinase inhibitor, (L)-HIV-TAT 48-57-PP-JBD 20, observed by the apparent diffusion coefficient mapping magnetic resonance imaging method

The present experiments were carried out to provide direct in vivo evidence for the involvement of c-Jun N-terminal kinase (JNK) in the induction of ischemic brain injury. Malonate, which produces lesions similar to those of focal ischemia-reperfusion by a reversible inhibition of succinate dehydrogenase in mitochondria, was injected into the left striatum in the rat brain without or with the simultaneous injection of a cell permeable peptidic JNK inhibitor, (L)-HIV-TAT 48-57-PP-JBD 20. Two regions of malonate-induced brain injury were visualized as a hyperintense region with surrounding hypointense regions by apparent diffusion coefficient mapping magnetic resonance imaging. The JNK inhibitor significantly counteracted both hyper- and hypointense regions at the early stage of brain injury. Histological examination clarified that the inhibitor suppressed the induction of coagulation necrosis and spongy degeneration at early and late stages.

Therapeutic Options in Prevention and Treatment of Aspartoacylase Gene Mutation Resulting Abnormalities in Canavan Disease

Canavan disease (CD) is an autosomal recessive disorder, caused by mutations in the aspartoacylase gene resulting enzyme deficiency. Patients with CD have accumulation of NAAG and NAA in the brain resulting elevated urinary NAAG and NAA. Aspartoacylase gene mutation in the mouse led to multiple genomic abnormalities. Pathophysiological processes implicated in CD include spongy degeneration of the brain possibly by the abnormal genes expression / metabolic levels of NAAG, NAA, aspartate, glutamate, glutamate transporter-EAAT4, GABA receptor-GABRA6 and GABA. In addition, high expression of cell death inducing agents includes serine proteinase inhibitor 2, caspase 11 and interleukin 1- beta. Osteoporosis is also an important consequence in the CD mouse. Each of these pathways offers potential therapeutic targets and pharmacological manipulation.

Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency

Canavan disease (CD) is an autosomal recessive disorder caused by aspartoacylase deficiency leading to accumulation of N-acetylaspartic acid and spongy degeneration of the brain. The mouse model for CD showed low levels of glutamate and γ-aminobutyric acid (GABA) in the brain. Whether the low levels of glutamate and GABA observed in the CD mouse brain lead to abnormal production of glutamate-GABA associated enzymes and resulting succinate production is not obvious. While glutamate dehydrogenase and α-ketoglutarate dehydrogenase complex activities are lower in the cerebellum and brain stem of the CD mouse, alanine aminotransferase and succinate semialdehyde dehydrogenase (SSADH) activities and succinate level are similar to the levels observed in the wild type. Deficiency of SSADH has been suggested to be associated with mental retardation and hypotonia, similar to the clinical features of CD. The normal SSADH activity in the CD mouse brain suggests that mental retardation and hypotonia seen in the CD mouse is not due to SSADH activity and if documented also in patients with CD.

A diet containing yam reduces the cognitive deterioration and brain lipid peroxidation in mice with senescence accelerated

SummaryThe aim of this study was to evaluate the effect of a diet rich in yam tuber material [Dioscorea alata L. Var. purpurea (M.) Pouch.] on the learning and memory ability of 2‐month‐old male senescence accelerated mice (SAMP8). The mice were fed with three different diets for 12 weeks; a casein diet (control group) and either a casein diet supplemented with 10% lyophilized or with hot‐air dried yam. Results of passive and active shuttle avoidance tests showed the mice fed with the diet containing yam had significantly better learning and memory ability than the control group. The thiobarbituric acid‐reactive substances (TBARS) in the hippocampus of the group fed lyophilized yam were significantly lower than the control and also the group fed a diet containing hot‐air dried yam, whereas the spongy degeneration and the lipofuscin percentage tended to be lower but not significantly different. It was suggested that lyophilized yam was more effective than hot‐air dried yam in reducing the lipid peroxidation, brain pathological changes and the deterioration in the learning and memory ability in mice possibly because lyophilized yam contains more antioxidant compounds.