Noradrenergic activation of glycogenolysis in the rat neocortex and hippocampus

Fara-On, Maria (2001) Noradrenergic activation of glycogenolysis in the rat neocortex and hippocampus. Masters thesis, Memorial University of Newfoundland.

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Abstract

In the central nervous system (CNS) glycogen and its catabolic enzyme glycogen phosphorylase (GP) are localized primarily in glial cells. Little is known about the distribution and localization of this energy source throughout the brain. Neuronally- secreted noradrenaline (NA) is known to activate glycogenolysis by stimulating adrenergic receptors (AR) found on glial ceils, however, many aspects of this metabolic interaction have yet to be elucidated. Using in vivo and in situ techniques, this study aims to map the discrete areas of the brain where high levels of both active (aGP) and available (tGP) glycogen phosphorylase exist, where NA exerts significant glycogenolytic effects and to identify which AR subtypes may be involved in mediating these effects. -- We investigated the effects of noradrenergic agents on glycogenolysis through IP administration of the α2 adrenergic autoreceptor antagonist, idazoxan (5 mg/kg), the α1-AR agonist, phenylephrine (3 mg/kg), or both á1- and β1/ β2-AR antagonists, prazosin (3 mg/kg) and propranolol (5 mg/kg). Drug effects on glycogenolysis were assayed by histochemical assessment of aGP and tGP no longer than 45 minutes following injection of drug or vehicle. Relative optical density (ROD) measures of regions of the neocortex, hippocampus, selected thalamic, diencephalic and striatal sites were taken using computer-assisted densitometric software (MCID). AGP and tGP were found to be distributed differentially throughout the sites investigated. Layer 4 of the neocortex, stratum lacunosum moleculare, medial habenula, reticular nucleus of the thalamus and the globus pallidus all demonstrated particularly high levels of both aGP and tGP under normal conditions. Idazoxan administration was found to induce significant increases in aGP levels in all layers of the upper limb of the primary somatosensory cortex, all layers of CA1, and some layers in CA3 and dentate gyrus, all thalamic nuclei examined and the caudate putamen. Results from our receptor study using specific AR subtype agonists and antagonists were inconclusive, but idazoxan was a much more effective activator than phenylephrine supporting the hypothesis that à, rather than á-ARs, play the primary role in mediating glycogenolysis induced by NA release. In addition the use of an á- and à-AR antagonist cocktail suggested noradrenergic modulation contributes only weakly to basal enzymic activation. The range of glycogenolytic activation/inhibition induced by adrenergic agents appears to be 0-12% of total available GP. -- The distribution of aGP and tGP we have found is consistent with the aGP distribution previously described by Harley and Bielajew (1992). Levels of aGP in the absence of drug manipulation appear to be less than 80% of tGP. Our neocortical results are also consistent with previous data showing significant increases in aGP in the somatosensory cortex following medial forebrain bundle (MFB) stimulation, suggesting an important interaction between sensory processing and noradrenergic modulation of glycogenolysis. The novel finding that NA induces significant activation of glycogenolysis in the hippocampus suggests activation of glycogenolysis may play a part in NA's learning and mnemonic effects in this region.

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