Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma

Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca 2+ flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes. The inhibitors employed were the voltage gated Ca 2+ channel inhibitor Lomerizine (Lom), the Ca 2+ permeable AMPA receptor inhibitor YM872 and the P2X 7 receptor inhibitor oxATP. Results: Following partial optic nerve transection, hyper-phosphorylation of Tau and acetylated tubulin immunoreactivity were increased, and Nogo-A immunoreactivity was decreased, indicating that axonal changes occurred acutely. All combinations of ion channel inhibitors reduced hyper-phosphorylation of Tau and increased Nogo-A immunoreactivity at day 3 after injury. However, only Lom/oxATP or all three inhibitors in combination significantly reduced acetylated tubulin immunoreactivity. Most combinations of ion channel inhibitors were effective in restoring the lengths of the paranode and the paranodal gap, indicative of the length of the node of Ranvier, following injury. However, only all three inhibitors in combination restored to normal Ankyrin G length at the node of Ranvier. Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion channel inhibitors in combination. Conclusions: Data indicate that inhibiting any of a range of ion channels preserves certain elements of axon and node structure and limits some oxidative damage following injury, whereas ionic flux through all three channels must be inhibited to prevent lipid peroxidation and preserve Ankyrin G distribution and OPCs

Kall potatis i forskningens namn: Konstruktion av ett kompendium som stöder utveckling av processkunskap inom biologiundervisningen i gymnasieskolan

Inom ramen för examensarbetet konstruerades ett kompendium som ska förmedla kunskap om den vetenskapliga processen genom integration av autentiska experiment i skolan. Materialet ska hjälpa eleverna att konstruera sina egna experiment och samtidigt bli medvetna om ”tänkandet bakom görandet”. Kompendiet riktar sig till elever i gymnasieskolans biologiundervisning, och kan med fördel användas inom kursen biologi breddning. Den experimentella metoden som används är blodsockermätningar med eleven själv som mätsystem. Den är enkel att genomföra, och kan anknytas till olika frågeställningar som kan väcka elevernas intresse. Kompendiets konstruktion tar sin utgångspunkt i aktuell forskning, och kan ses som ett första steg att integrera kunskap om ”the Nature of Science” i naturvetenskaplig undervisning i skolan

Two populations of glial cells from fish optic nerve/tract with distinct electrophysiological properties

The electrophysiological properties of the two major glial cell types in cultures from the regenerating goldfish optic nerve/tract were studied with patch-clamp techniques. Spindle-shaped cells express myelin proteins. These oligodendrocyte-like cells possess outwardly rectifying currents, do not show glutamate activated currents and are rarely electrically coupled to neighboring cells. Cells of epitheloid morphology probably represent astrocytes. They are GFAP-positive and do not exhibit myelin proteins. These cells have glutamate activated currents, display a linear current to voltage relationship and are extensively electrically coupled thus displaying properties similar to mammalian astrocytes

Two populations of glial cells from fish optic nerve/tract with distinct electrophysiological properties

The electrophysiological properties of the two major glial cell types in cultures from the regenerating goldfish optic nerve/tract were studied with patch-clamp techniques. Spindle-shaped cells express myelin proteins. These oligodendrocyte-like cells possess outwardly rectifying currents, do not show glutamate activated currents and are rarely electrically coupled to neighboring cells. Cells of epitheloid morphology probably represent astrocytes. They are GFAP-positive and do not exhibit myelin proteins. These cells have glutamate activated currents, display a linear current to voltage relationship and are extensively electrically coupled thus displaying properties similar to mammalian astrocytes