I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Thioflavine T (ThT) associates rapidly with aggregated fibrils of the synthetic beta/A4-derived peptides beta(1-28) and beta(1-40), giving rise to a new excitation (ex) (absorption) maximum at 450 nm and enhanced emission (em) at 482 nm, as opposed to the 385 nm (ex) and 445 nm (em) of the free dye. This change is dependent on the aggregated state as monomeric or dimeric peptides do not react, and guanidine dissociation of aggregates destroys the signal. There was no effect of high salt concentrations. Binding to the beta(1-40) is of lower affinity, Kd 2 microM, while it saturates with a Kd of 0.54 microM for beta(1-28). Insulin fibrils converted to a beta-sheet conformation fluoresce intensely with ThT. A variety of polyhydroxy, polyanionic, or polycationic materials fail to interact or impede interaction with the amyloid peptides. This fluorometric technique should allow the kinetic elucidation of the amyloid fibril assembly process as well as the testing of agents that might modulate their assembly or disassembly.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/pro.5560020312

Thioflavine T interaction with synthetic Alzheimer's disease beta-amyloid peptides: detection of amyloid aggregation in solution.

Molecular mechanism of Thioflavin-T binding to amyloid fibrils.

Publisher Summary Despite the presence of a significant amount of carbohydrate in these fibrils, the staining reaction was eventually shown to be because of the protein component. The histologic benzothiazole dyes thioflavin S (ThS) and thioflavin T (ThT) under the appropriate conditions selectively stain amyloid structures in a number of pathological settings, as does the diazobenzidine sulfonate dye, Congo red, which is also birefringent when bound to fibrils. Phorwhite BBU, Sirius Red, and several other fluorescent and nonfluorescent aromatic molecules also show this property. Investigation of the amyloid fibril formation process requires not only the ability to distinguish the characteristic amyloid B-sheet structure from amorphous aggregates of the monomer or nonamyloid fibril forms of the precursor protein, but quantitation of the amyloid form as well. Congo red and thioflavin T undergo characteristic spectral alterations on binding to a variety of amyloid fibrils that do not occur on binding to the precursor polypeptides, monomers, or amorphous aggregates of peptide. Both dyes have been adapted to in vitro measurements of amyloid fibril formation.

Quantification of beta -sheet amyloid fibril structures with thioflavin t

Neurotrophins have diverse functions in the CNS. Initially synthesized as precursors (proneurotrophins), they are cleaved to produce mature proteins, which promote neuronal survival and enhance synaptic plasticity by activating Trk receptor tyrosine kinases. Recent studies indicate that proneurotrophins serve as signalling molecules by interacting with the p75 neurotrophin receptor (p75NTR). Interestingly, proneurotrophins often have biological effects that oppose those of mature neurotrophins. Therefore, the proteolytic cleavage of proneurotrophins represents a mechanism that controls the direction of action of neurotrophins. New insights into the 'yin and yang' of neurotrophin activity have profound implications for our understanding of the role of neurotrophins in a wide range of cellular processes.

/pdf/the-yin-and-yang-of-neurotrophin-action-4q1o03a9lh.pdf

The yin and yang of neurotrophin action

Neurotrophins cooperate with neural activity to modulate CNS neuronal survival and dendritic differentiation. In a previous study, we demonstrated that a critical balance of neurotrophin and neural activity is required for Purkinje cell survival in cocultures of purified granule and Purkinje cells (Morrison and Mason, 1998). Here we investigate whether TrkB signaling regulates dendrite and spine development of Purkinje cells. BDNF treatment of purified Purkinje cells cultured alone did not elicit formation of mature dendrites or spines. In cocultures of granule and Purkinje cells, however, continuous treatment with BDNF over a 2 week postnatal culture period increased the density of Purkinje cell dendritic spines relative to controls without causing a shift in the proportions of headed and filopodia-like spines. The increase in spine number was blocked by adding TrkB-IgG to the medium together with BDNF. Although BDNF alone did not consistently modify the morphology of dendritic spines, treatment with TrkB-IgG alone yielded spines with longer necks than those in control cultures. None of these treatments altered Purkinje cell dendritic complexity. These analyses reveal a role for TrkB signaling in modulating spine development, consistent with recently reported effects of neurotrophins on synaptic function. Moreover, spine development can be uncoupled from dendrite outgrowth in this reductionist system of purified presynaptic and postsynaptic neurons.

https://www.jneurosci.org/content/jneuro/18/21/8559.full.pdf

TrkB Signaling Modulates Spine Density and Morphology Independent of Dendrite Structure in Cultured Neonatal Purkinje Cells

We developed a novel inbred strain of mouse with age-related brain atrophy and it was named "Senescence Accelerated Mouse (SAM)-P/10." Macroscopic morphometry indicated that the brains of SAM-P/10 showed age-dependent involutional changes mainly in the frontal portion of the cerebrum. The brain weight decreased by 8.6% throughout the life-span. There were no obvious defects in postnatal development. Semi-macroscopic morphometry revealed a prominent atrophy in the neocortex, olfactory cortex and amygdala. Microscopic morphometry showed that the neocortical neurons were lost with aging, with mostly the large neurons being affected which were lost by 35.6% throughout the life-span. Somata of the neocortical neurons shrank with advancing age. In a control SAM-R/1 strain with only a slight macroscopic involutional change in the brain without weight loss, neither loss of the neocortical large neurons nor shrinkage of the neocortical neurons was evident with aging. Learning and memory skills were evaluated using the one-trial passive avoidance task and conditional avoidance task. Young SAM-P/10 mice performed well in both tasks but older SAM-P/10 showed a poorer performance in both tasks, and this was even poorer than the performance of very old SAM-R/1 mice. Thus, SAM-P/10 can serve as a spontaneous animal model of brain atrophy for a variety of studies of aging of the brain. A better understanding of neurodegenerative diseases with dementia should be forthcoming.

Inbred SAM-P/10 as a mouse model of spontaneous, inherited brain atrophy.

Oxidative stress, an imbalance between endogenous levels of oxygen radicals and antioxidative defense, increases with aging. However, it is not clear which of these two factors is the more critical. To clarify the production of oxygen radicals increases with age, we examined oxygen radical-dependent chemiluminescent signals in ex vivo brain slices using a novel photonic imaging method. The chemiluminescent intensity was significantly decreased by the membrane permeable superoxide dismutase (SOD)/catalase mimic, but not by Cu,Zn-SOD. Inhibitors for complex I, III, and IV of the mitochondrial electron transport chain transiently enhanced the chemiluminescent signal. The superoxide-dependent chemiluminescent intensity in senescence accelerated mouse (SAM) brain tissues increases with age. Moreover, the slope of the age-dependent increase was steeper in SAMP10, a strain characterized by a short lifespan and atrophy in the frontal cerebral cortex, than the senescence-resistant strain SAMR1, which has a longer lifespan. An increase in chemiluminescence with age was also observed in C57/BL6 mice, Wistar rats, and pigeons, although levels of chemiluminescence were lower in the pigeons than murines. The rate of age-related increases of superoxide-dependent chemiluminescence was inversely related to the maximum lifespan of the animals. The activity of superoxide dismutase was unchanged during the aging process in the brain. This suggested that superoxide production itself may increase with age. We speculated that reactive oxygen may be a signal to determine the aging process.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1474-9726.2008.00394.x

Age-related increase of superoxide generation in the brains of mammals and birds

Methods in laboratory investigation : fluroremetric examination of tissue amyloid fibrils in murine senile amyloidosis : use of the fluorescent indicator, thioflavine T

Atsuyoshi Shimada

Papers

TrkB Signaling Modulates Spine Density and Morphology Independent of Dendrite Structure in Cultured Neonatal Purkinje Cells

Inbred SAM-P/10 as a mouse model of spontaneous, inherited brain atrophy.

Age-related increase of superoxide generation in the brains of mammals and birds

Methods in laboratory investigation : fluroremetric examination of tissue amyloid fibrils in murine senile amyloidosis : use of the fluorescent indicator, thioflavine T

Fluorometric Examination of Tissue Amyloid Fibrils in Murine Senile Amyloidosis: Use of the Fluorescent Indicator, Thioflavine T