We studied the ability of four non-conjugated alpha7-subunit fragments of the nicotinic acetylcholine receptor to induce an immune response and to protect memory in olfactory bulbectomized mice which demonstrate abnormalities similar to Alzheimer's disease (AD). Vaccination only with the alpha7-subunit fragment 173-193 was shown to rescue spatial memory, to restore the level of alpha7 acetylcholine receptors in the cortex, and to prevent an increase in the amyloid-beta (Abeta) level in brain tissue in these animals. Antibodies against the peptide 173-193 were revealed in blood serum and cerebrospinal liquid in the bulbectomized mice. Passive immunization with mouse blood sera containing antibodies to the peptide 173-193 also restored memory in bulbectomized animals. The observed positive effect of both active and passive immunization with the fragment of alpha7-subunit on memory of bulbectomized mice provides a new insight into an anti-AD drug design.
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http://dx.doi.org/10.3233/JAD-2010-091474 | DOI Listing |
Prog Neuropsychopharmacol Biol Psychiatry
November 2024
Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
The brain's Renin-Angiotensin System plays an important role in the modulation of mental state. Previously we demonstrated that activated angiotensin (Ang) converting enzyme (ACE) 2, which converts Ang II into Ang (1-7), or the intracerebroventricular administration of Ang (1-7) produced an antidepressant-like effect in mice via Mas receptors (MasR). Since the ACE inhibitor Captopril (Cap) increases Ang (1-7) in the brain, it remains unknown whether Cap affects the depressive-like behavior of olfactory bulbectomized (OBX) mice, an animal model of depression.
View Article and Find Full Text PDFHippocampus
December 2024
Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
The hippocampus is important for social behavior and exhibits unusual structural plasticity in the form of continued production of new granule neurons throughout adulthood, but it is unclear how adult neurogenesis contributes to social interactions. In the present study, we suppressed neurogenesis using a pharmacogenetic mouse model and examined social investigation and aggression in adult male mice to investigate the role of hippocampal adult-born neurons in the expression of aggressive behavior. In simultaneous choice tests with stimulus mice placed in corrals, mice with complete suppression of adult neurogenesis in adulthood (TK mice) exhibited normal social investigation behaviors, indicating that new neurons are not required for social interest, social memory, or detection of and response to social olfactory signals.
View Article and Find Full Text PDFMol Neurobiol
July 2024
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia.
After olfactory bulbectomy, animals are often used as a model of major depression or sporadic Alzheimer's disease and, hence, the status of this model is still disputable. To elucidate the nature of alterations in the expression of the genome after the operation, we analyzed transcriptomes of the cortex, hippocampus, and cerebellum of the olfactory bulbectomized (OBX) mice. Analysis of the functional significance of genes in the brain of OBX mice indicates that the balance of the GABA/glutamatergic systems is disturbed with hyperactivation of the latter in the hippocampus, leading to the development of excitotoxicity and induction of apoptosis in the background of severe mitochondrial dysfunction and astrogliosis.
View Article and Find Full Text PDFPLoS One
February 2024
Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Alzheimer's disease (AD) is a complex neurodegenerative disorder with both genetic and non-genetic causes. Animal research models are available for a multitude of diseases and conditions affecting the central nervous system (CNS), and large-scale CNS gene expression data exist for many of these. Although there are several models specifically for AD, each recapitulates different aspects of the human disease.
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