Neuroscience
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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.
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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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Huntington's disease is a fatal neurodegenerative disorder caused by a mutation of the huntingtin gene and involves progressive motor abnormalities (including chorea), cognitive deficits (dementia) as well as psychiatric symptoms. We have previously demonstrated that environmental enrichment slows the onset and progression of Huntington's disease in transgenic mice. Here, we investigated the effects of enhanced physical exercise on disease progression and brain-derived neurotrophic factor expression. ⋯ Brain-derived neurotrophic factor mRNA levels were reduced in the anterior cortex, striatum and hippocampus of Huntington's disease mice, and only striatal deficits were ameliorated by running. Overall, we show that voluntary physical exercise delays the onset of Huntington's disease and the decline in cognitive ability. In addition, our results reveal that some aspects of hippocampal dependent memory are not entirely reliant on sustained hippocampal brain-derived neurotrophic factor expression.
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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
Corticotropin-releasing factor in the dorsal raphe elicits temporally distinct serotonergic responses in the limbic system in relation to fear behavior.
The neurotransmitters serotonin and corticotrophin-releasing factor are thought to play an important role in fear and anxiety behaviors. This study aimed to determine the relationship between corticotrophin-releasing factor-evoked changes in serotonin levels within discrete regions of the limbic system and the expression of fear behavior in rats. ⋯ In contrast, cessation of freezing behavior correlated with a delayed and prolonged increase in serotonin release within the medial prefrontal cortex. Our findings suggest that corticotrophin-releasing factor-induced freezing behavior is associated with regionally and temporally distinct serotonergic responses in the limbic system that may reflect differing roles for these regions in the expression of fear/anxiety behavior.