المؤلفون: Toshitaka Nabeshima, Tursun Alkam

مصطلحات موضوعية: Hallucinogen, medicine.medical_specialty, Schizophrenia (object-oriented programming), Behavioral methods, Disease, 030227 psychiatry, 03 medical and health sciences, 0302 clinical medicine, Delusion, Neuroimaging, mental disorders, medicine, Disorganized speech, medicine.symptom, Psychology, Psychiatry, Dopamine hypothesis of schizophrenia, 030217 neurology & neurosurgery

الوصف: The positive symptoms of schizophrenia such as disorganized speech, delusions, and hallucinations seem to unique to humans. Current research on schizophrenia in general has remained very challenging, thanks to growing numbers in theories about the cause and progression of the disease. A lack of behavioral methods to selectively study positive symptom-like behaviors or alternative behaviors has made it even more challenging to develop animal models with rational pathology of schizophrenia. However, emerging neuroimaging findings and rich information obtained from several decades of hallucinogen studies are encouraging to establish animal models to explore various causative theories for positive symptoms in schizophrenia. In this chapter, we review neuroimaging and pharmacological findings related to delusions and hallucinations and briefly introduce behavioral methods to investigate positive symptom-related behaviors in animal models of schizophrenia.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::635934b04edef8dbd97544779e9e5ed1Test
https://doi.org/10.1016/b978-0-12-800981-9.00004-3Test

المؤلفون: Hiroko Tsunekawa, Tursun Alkam, Eiichi Someya, Kiyofumi Yamada, Emiko Fukuzaki, Akihiro Mouri, Hiroyuki Mizoguchi, Toshitaka Nabeshima, Daisuke Ibi, Kazuhiro Takuma, Ko Hei Akazawa, Yukihiro Noda

المصدر: Journal of Pharmacology and Experimental Therapeutics. 331:14-22

مصطلحات موضوعية: Male, Amyloid beta, Matrix metalloproteinase inhibitor, Hippocampus, Matrix Metalloproteinase Inhibitors, Pharmacology, Matrix metalloproteinase, Mice, In vivo, mental disorders, medicine, Animals, Protease Inhibitors, Cells, Cultured, Mice, Knockout, Mice, Inbred ICR, Amyloid beta-Peptides, biology, Chemistry, Neurotoxicity, medicine.disease, In vitro, Matrix Metalloproteinase 9, nervous system, Knockout mouse, biology.protein, Molecular Medicine, Cognition Disorders, Neuroscience

الوصف: In Alzheimer's disease (AD), the expression of matrix metalloproteases (MMPs), which are capable of degrading extracellular matrix proteins, is increased in the brain. Previous studies with cultured glial cells have demonstrated that amyloid beta (Abeta) protein can induce the expression of MMPs, which could be involved in the degradation of Abeta. In the present study, we investigated the role of MMP-2 and MMP-9 in cognitive impairment induced by the injection of Abeta in mice. The intracerebroventricular injection of Abeta25-35, Abeta1-40, and Abeta1-42, but not Abeta40-1, transiently increased MMP-9, but not MMP-2, activity and protein expression in the hippocampus. Immunohistochemistry revealed the expression of MMP-9 to be increased in both neurons and glial cells in the hippocampus after Abeta treatment. The Abeta-induced cognitive impairment in vivo as well as neurotoxicity in vitro was significantly alleviated in MMP-9 homozygous knockout mice and by treatment with MMP inhibitors. These results suggest the increase in MMP-9 expression in the hippocampus to be involved in the development of cognitive impairment induced by Abeta1-40. Thus, specific inhibitors of MMP-9 may have therapeutic potential for the treatment of AD. Our findings suggest that, as opposed to expectations based on previous findings, MMP-9 plays a causal role in Abeta-induced cognitive impairment and neurotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee073a2f30c4a86ff025e45bc33c4989Test
https://doi.org/10.1124/jpet.109.154724Test

المؤلفون: Atsumi Nitta, Mitsuru Seshima, Toshitaka Nabeshima, Kuniaki Saito, Kiyofumi Yamada, Hiroyuki Mizoguchi, Tursun Alkam, Akio Itoh

المصدر: Behavioural Brain Research. 189:100-106

مصطلحات موضوعية: Male, medicine.medical_specialty, Amyloid beta, medicine.medical_treatment, Neurotoxins, Nitric Oxide Synthase Type II, Hippocampus, Hippocampal formation, Mice, Behavioral Neuroscience, Species Specificity, Alzheimer Disease, Internal medicine, mental disorders, medicine, Animals, RNA, Messenger, Injections, Intraventricular, Antibacterial agent, Mice, Knockout, Mice, Inbred ICR, Amyloid beta-Peptides, biology, Tumor Necrosis Factor-alpha, business.industry, Recognition, Psychology, Peptide Fragments, Thalidomide, Mice, Inbred C57BL, Nitric oxide synthase, Endocrinology, Cytokine, Toxicity, biology.protein, Tumor necrosis factor alpha, business, Immunosuppressive Agents

الوصف: No effective remedy has currently been realized to prevent the cognitive impairments of Alzheimer's disease (AD). The interruption of the toxic pathways of amyloid beta peptide (Abeta) still remains promising for the treatment. The involvement of tumor necrosis factor-alpha (TNF-alpha) in the toxicity of Abeta(1-40) in recent reports provide a fresh target for the interruption. In the current study, we evaluated the feasibility of a strategy that target TNF-alpha to prevent the impairment of memory induced by Abeta. The i.c.v-injection of Abeta(25-35) increased the hippocampal mRNA expression of both TNF-alpha and inducible nitric oxide synthase (iNOS), of which the former was stronger. The knock-out of TNF-alpha (TNF-alpha (-/-)) in mouse prevented the increase of iNOS mRNA induced by Abeta(25-35). Not only the inhibition of iNOS activity but also TNF-alpha (-/-) prevented the nitration of proteins in the hippocampus and the impairment of recognition memory in mice induced by Abeta(25-35). Daily treatment with thalidomide (20 mg/kg), a preferential degrader of TNF-alpha mRNA, or i.c.v.-injection of an anti-TNF-alpha antibody (10 etag/mouse) prevented the nitration of proteins in the hippocampus and the impairment of recognition memory induced by Abeta(25-35) or Abeta(1-40) in mice. These results suggested the practicability of targeting TNF-alpha as a preventive strategy against Abeta-mediated cognitive impairments.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4bf4a1d219cd14592b99fcc5ff77d22Test
https://doi.org/10.1016/j.bbr.2007.12.014Test

المؤلفون: Hiroyuki Mizoguchi, Toshitaka Nabeshima, Akio Itoh, Atsumi Nitta, Tursun Alkam

المصدر: Behavioural Brain Research. 180:139-145

مصطلحات موضوعية: Male, inorganic chemicals, Amyloid beta, Blotting, Western, Hippocampus, Neuropsychological Tests, Pharmacology, Depsides, Mice, Behavioral Neuroscience, chemistry.chemical_compound, Peroxynitrous Acid, mental disorders, medicine, Animals, Memory impairment, Drug Interactions, Memory disorder, Maze Learning, Analysis of Variance, Memory Disorders, Mice, Inbred ICR, Amyloid beta-Peptides, Behavior, Animal, Dose-Response Relationship, Drug, biology, Chemistry, Rosmarinic acid, Neurotoxicity, medicine.disease, Dose–response relationship, Neuroprotective Agents, Cinnamates, biology.protein, Neuroscience, Peroxynitrite

الوصف: Peroxynitrite (ONOO(-))-mediated damage is regarded to be responsible for the cognitive dysfunction induced by amyloid beta protein (Abeta) in Alzheimer's disease (AD). In the present study, we examined the protective effects of rosmarinic acid (RA), a natural scavenger of ONOO(-), on the memory impairment in a mouse model induced by acute i.c.v. injection of Abeta(25-35). Mice daily received i.p. several doses of RA after the injection of Abeta(25-35). RA prevented the memory impairments induced by Abeta(25-35) in the Y maze test and novel object recognition task. RA, at the effective lowest dose (0.25mg/kg), prevented Abeta(25-35)-induced nitration of proteins, an indirect indicator of ONOO(-) damage, in the hippocampus. At this dose, RA also prevented nitration of proteins and impairment of recognition memory induced by ONOO(-)-i.c.v.-injection. Co-injection of the non-memory-impairing dose of ONOO(-) with Abeta(25-35) blocked the protective effects of RA (0.25mg/kg). These results demonstrated that the memory protective effects of RA in the neurotoxicity of Abeta(25-35) is due to its scavenging of ONOO(-), and that daily consumption of RA may protect against memory impairments observed in AD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a508d522dcb66094e087335a59f7d873Test
https://doi.org/10.1016/j.bbr.2007.03.001Test