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  • Changes in ventral respiratory column GABAaR ε- and δ-subunits during hibernation mediate resistance to depression by EtOH and pentobarbital. 21084677

    During hibernation in the 13-lined ground squirrel, Ictidomys tridecemlineatus, the cerebral cortex is electrically silent, yet the brainstem continues to regulate cardiorespiratory function. Previous work showed that neurons in slices through the medullary ventral respiratory column (VRC) but not the cortex are insensitive to high doses of pentobarbital during hibernation, leading to the hypothesis that GABA(A) receptors (GABA(A)R) in the VRC undergo a seasonal modification in subunit composition. To test whether alteration of GABA(A)R subunits are responsible for hibernation-associated pentobarbital insensitivity, we examined an array of subunits using RT-PCR and Western blots and identified changes in ε- and δ-subunits in the medulla but not the cortex. Using immunohistochemistry, we confirmed that during hibernation, the expression of ε-subunit-containing GABA(A)Rs nearly doubles in the VRC. We also identified a population of δ-subunit-containing GABA(A)Rs adjacent to the VRC that were differentially expressed during hibernation. As δ-subunit-containing GABA(A)Rs are particularly sensitive to ethanol (EtOH), multichannel electrodes were inserted in slices of medulla and cortex from hibernating squirrels and EtOH was applied. EtOH, which normally inhibits neuronal activity, excited VRC but not cortical neurons during hibernation. This excitation was prevented by bicuculline pretreatment, indicating the involvement of GABA(A)Rs. We propose that neuronal activity in the VRC during hibernation is unaffected by pentobarbital due to upregulation of ε-subunit-containing GABA(A)Rs on VRC neurons. Synaptic input from adjacent inhibitory interneurons that express δ-subunit-containing GABA(A)Rs is responsible for the excitatory effects of EtOH on VRC neurons during hibernation.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple

  • Postsynaptic dorsal column neurons express NK1 receptors following colon inflammation. 12559111

    Recent clinical and experimental studies have suggested that the dorsal column pathway and specifically postsynaptic dorsal column neurons play an important role in the transmission of visceral pain. In our study we have mapped the distribution of postsynaptic dorsal column neurons in thoracic, lumbar and sacral spinal cord segments. The presence of immunoreactivity for neurokinin 1 receptors on these postsynaptic dorsal column neurons was examined under control conditions and after colon inflammation. The largest number of postsynaptic dorsal column neurons was found in the lumbar enlargement. They were mostly located in laminae III-IV, but depending on the spinal segment, about 7-15% of them were in the deep medial dorsal horn and in the central canal area. Under control conditions none of the 1438 postsynaptic dorsal column neurons examined expressed neurokinin 1 receptors. However, after induction of colon inflammation about 1.4% of the 2015 postsynaptic dorsal column neurons observed in the experimental group showed immunoreactivity for neurokinin 1 receptors. These neurons were preferentially found in the lower thoracic and lumbosacral spinal segments where they represented about 3-4% of the total population of postsynaptic dorsal column neurons examined. The de novo expression of neurokinin1 receptors on postsynaptic dorsal column neurons after colon inflammation suggests that substance P released from visceral primary afferents under inflammatory conditions could help produce central sensitization of these neurons.
    Document Type:
    Reference
    Product Catalog Number:
    AB5060
    Product Catalog Name:
    Anti-Substance P Receptor Antibody, pain

  • Age-related intra-axonal accumulation of neurofilaments in the dorsal column nuclei of the cat brainstem: a light and electron microscopic immunohistochemical study. 9666164

    In the present study, we examined the age-related intra-axonal accumulation of neurofilaments in the dorsal column nuclei of the cat by using immunohistochemical techniques combined with light and electron microscopy. Light microscopic analysis revealed oval or circular immunostained structures in the dorsal column nuclei of old cats. These immunostained structures were not observed in the material obtained from adult controls. Under the electron microscope, it was discovered that the immunostained structures were greatly enlarged axons with disrupted myelin sheaths. These enlarged axons contained massive accumulations of neurofilaments, some mitochondria, vacuoles and dense granules. The abnormalities of the myelin sheaths included the breaking of myelin at several locations, a splitting and ballooning in the myelin lamellae of the sheath and a distended periaxonal space between the axon and myelin sheaths. These ultrastructural changes resembled the degenerative alterations that have been observed in the axons of human and animals suffering from a number of pathological conditions, including giant axonal neuropathy and toxic neuropathy. Therefore, severely altered axons with intra-axonal accumulation of neurofilaments appear to reflect chronic degenerative changes that are a component of the aging process.
    Document Type:
    Reference
    Product Catalog Number:
    AB1987
    Product Catalog Name:
    Anti-Neurofilament M (145 kDa) Antibody, CT