Neuroscience
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Comparative Study
Hypoxia/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone.
Neurons and oligodendrocyte progenitors are highly sensitive to perinatal hypoxic-ischemic injury. As accumulating evidence suggests that many insults to the human infant occur in utero, and preventing brain damage to infants in utero will prove difficult, there is strong rationale to pursue regenerative strategies to reduce the morbidity associated with developmental brain injuries. The purpose of this study was to determine whether a hypoxic-ischemic insult stimulates the neural stem/progenitor cells in the subventricular zone to generate new neurons and oligodendrocytes. ⋯ Hypoxia-ischemia also increases neurogenesis in vivo. Doublecortin positive cells with migratory profiles were observed streaming from the ipsilateral subventricular zone to the striatum and neocortex, whereas, few doublecortin positive cells were found in the contralateral hemisphere after hypoxia-ischemia. These observations provide evidence that the somatic neural progenitors of the subventricular zone participate in the production of new brain cells lost after hypoxia-ischemia.
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Comparative Study
Cellular and subcellular localization of PDE10A, a striatum-enriched phosphodiesterase.
PDE10A is a recently identified phosphodiesterase that is highly expressed by the GABAergic medium spiny projection neurons of the mammalian striatum. Inhibition of PDE10A results in striatal activation and behavioral suppression, suggesting that PDE10A inhibitors represent a novel class of antipsychotic agents. In the present studies we further elucidate the localization of this enzyme in striatum of rat and cynomolgus monkey. ⋯ Immuno-electron microscopy of striatum confirms that PDE10A is most often associated with membranes in dendrites and spines. Immuno-gold particles are observed on the edge of the postsynaptic density but not within this structure. Our studies indicate that PDE10A is associated with post-synaptic membranes of the medium spiny neurons, suggesting that the specialized compartmentation of PDE10A enables the regulation of intracellular signaling from glutamatergic and dopaminergic inputs to these neurons.
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Comparative Study
Presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors modulate release of inhibitory amino acids in rat spinal cord dorsal horn.
Local inhibition within the spinal cord dorsal horn is mediated by the neurotransmitters GABA and glycine and strongly influences nociceptive and temperature signaling. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are expressed by inhibitory interneurons and have been shown to modulate GABA release in other regions of the CNS. In the spinal cord, there is morphological evidence for presynaptic AMPA receptor subunits in GABAergic dorsal horn neurons, but functional data are lacking. ⋯ In addition, we have observed AMPA-induced depression of evoked release of GABA and glycine onto lamina I NK1R+ neurons. Taken together these data support a role for presynaptic AMPA receptors in modulating release of GABA and glycine in the superficial dorsal horn. Because inhibition in the dorsal horn is important for controlling pain signaling, presynaptic AMPA receptors acting to modulate the inhibitory inputs onto dorsal horn neurons would be expected to impact upon pain signaling in the spinal cord dorsal horn.
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Comparative Study
Characterization of neurons that express preprotachykinin B in the dorsal horn of the rat spinal cord.
Although it is established that neurokinin B is expressed by some neurons in laminae I-III of the rat spinal dorsal horn, little is known about the proportions of cells in these laminae that express neurokinin B, or whether these are excitatory or inhibitory neurons. Neurokinin B is derived from preprotachykinin B, and we have used an antibody against preprotachykinin B to address these issues. We found that preprotachykinin B-immunoreactive neurons were present throughout laminae I-III, constituting 10-11% of the neuronal population in laminae I-II, and 4% of that in lamina III. ⋯ However, there was little or no overlap between preprotachykinin B and three other markers associated with excitatory neurons in these laminae: the mu opioid receptor MOR-1, the neurokinin 1 receptor and neurotensin. These results suggest that neurokinin B is expressed by specific populations of excitatory neurons in the superficial dorsal horn. By examining expression of Fos protein in response to intraplantar injection of formaldehyde we provide evidence that many of the preprotachykinin B cells in lamina I and the outer part of lamina II respond to noxious stimulation.
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Insulin peptide, acting through tyrosine kinase receptor pathways, contributes to nerve development or repair. In this work, we examined the direction, impact and repertoire of insulin signaling in vivo during peripheral nerve regeneration in rats. First, we demonstrated that insulin receptor is expressed on lumbar dorsal root ganglia neuronal perikarya using immunohistochemistry. ⋯ Intrathecal insulin delivery was associated with greater recovery of thermal sensation and longer distances to stimulus response with the pinch test following sural nerve crush. Insulin signaling at neuron perikarya can drive distal sensory axon regrowth, rescue retrograde alterations of axons and alter axon peptide expression. Moreover, such actions are associated with upregulation of its own receptor.