Neuroscience
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Comparative Study
Caspase-3 cleaved spectrin colocalizes with neurofilament-immunoreactive neurons in Alzheimer's disease.
Corticocortical disconnection in Alzheimer's disease occurs by the progressive impairment and eventual loss of a small subset of pyramidal neurons in layers III and V of association areas of the neocortex. These neurons exhibit large somatic size, extensive dendritic arborization and high levels of nonphosphorylated neurofilaments of medium and high molecular weight that can be identified using a monoclonal SMI-32 antibody. It is thought that the accumulation of amyloid Abeta and neurofibrillary tangles may provoke metabolic disturbances that result in the loss of these SMI-32 immunoreactive neurons. ⋯ In the present study, we utilized an antibody that selectively recognizes the 120 kDa breakdown product of alphaIIspectrin (fodrin) generated by caspase-3 to determine whether this protease is activated in vulnerable pyramidal neurons located in layers III and V of Alzheimer's disease brains. Neurons immunoreactive for caspase-3 cleaved alphaIIspectrin were located predominantly in layers III and V of the inferior frontal and superior temporal cortices of patients with Alzheimer's disease but not age-matched controls. Pyramidal neurons immunoreactive for caspase-3 cleaved alphaIIspectrin invariably displayed SMI-32 immunoreactivity suggesting that caspase-3 activation is a pathological event that may be responsible for the loss of a subset of pyramidal neurons that comprise corticocortical projections.
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Comparative Study
Volatile female odors activate the accessory olfactory system of male mice without physical contact.
We previously reported that male mice are more attracted to volatile odors from intact female mice than from ovariectomized female mice. In the present study, we investigated male attraction to volatile odors from soiled bedding collected from the cages of estrous or ovariectomized female mice. There was no difference in the total time spent sniffing volatile odors from estrous and ovariectomized female mice, suggesting that female mice emit volatile odors which are not excreted into bedding. ⋯ To characterize the female-specific volatile odors, we conducted habituation-dishabituation tests. Whereas sham-operated male mice discriminated between volatile odors of estrous and ovariectomized female mice, vomeronasal organ-removed male mice did not. These results suggest that male mice discriminated whether or not female mice were ovariectomized, by volatile odors via the accessory olfactory system, and that the female-specific volatile odors are involved in reproduction.
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Comparative Study
Regions of alpha-amino-5-methyl-3-hydroxy-4-isoxazole propionic acid receptor subunits that are permissive for the insertion of green fluorescent protein.
The green fluorescent protein can be fused to the ends of a mature glutamate receptor subunit to produce functional, fluorescent receptors. However, there are good reasons to search for internal regions of receptor subunits that can tolerate green fluorescent protein insertion. First, internal insertions of green fluorescent protein may produce functional, fluorescent subunits that traffic more correctly. ⋯ Finally, internal green fluorescent protein insertions could potentially produce subunits capable of signaling conformational changes through intrinsic changes in fluorescence intensity. To identify regions of receptor subunits that are permissive for green fluorescent protein insertion, we used a series of recombinant transposons to create fluorescent protein insertions in three alpha-amino-5-methyl-3-hydroxy-4-isoxazole propionic acid receptor subunits. A combined analysis of the relative fluorescence intensity and glutamate-gated ion channel function of 69 different green fluorescent protein fusion proteins identified permissive zones for the creation of bright and fully functional receptor subunits in the C-terminal portion of the amino terminal domain, the intracellular tail of the carboxy terminal domain, and within the pore-forming regions of the channel.
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Comparative Study
Activation and retrograde transport of protein kinase G in rat nociceptive neurons after nerve injury and inflammation.
Nerve injury elicits both universal and limited responses. Among the former is regenerative growth, which occurs in most peripheral neurons, and among the latter is the long-term hyperexcitability that appears selectively in nociceptive sensory neurons. Since positive injury signals communicate information from the site of an injury to the cell body, we hypothesize that a nerve injury activates both universal and limited positive injury signals. ⋯ In contrast, the extracellular signal-related kinases in the sensory axons were not activated by the complete Freund's adjuvant. These studies support the idea that the extracellular signal-related kinases are universal positive axonal signals and that protein kinase G is a limited positive axonal signal. They also establish the association between protein kinase G, the induction of long-term hyperexcitability, and chronic pain in rodents.
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Comparative Study
A role for glutamate and glia in the fast network oscillations preceding spreading depression.
The mechanism of the propagation of spreading depression is unclear. Classical theories proposed a self-maintained cycle fed by elevated potassium and/or glutamate in the extracellular space. Earlier we found in vivo a characteristic oscillatory field activity that is synchronous in a strip of tissue ahead of the oncoming wave of neuron depolarization and that occurs before the extracellular potassium level begins to rise [Herreras O, Largo C, Ibarz JM, Somjen GG, Marrín del Río R (1994) Role of neuronal synchronizing mechanisms in the propagation of spreading depression in the in vivo hippocampus. ⋯ Also, the amplitude of the population spikes within the burst diminished as individual cells fired fewer action potentials, although still phase-locked with population spikes. The effects of glial metabolic impairment were observed within the period when neuron electrical properties were still normal, and were blocked by glutamate receptor antagonists. These data suggest that glutamate released from glial cells and possibly also from neurons has a role in the generation of oscillations and neuron firing synchronization that precede the spreading depression-related depolarization, but additional mechanisms are required to fully explain the onset and propagation of spreading depression.