Vasoactive intestinal peptide (VIP) and noradrenaline (NA) have been previously shown to promote glycogenolysis in mouse cerebral cortex (Magistretti, 1990). This action, which is fully expressed within a few minutes, is exerted on astrocytes (Sorg and Magistretti, 1991). In the present article, we report a second, temporally delayed, action of VIP or NA in primary cultures of mouse cerebral cortical astrocytes; thus, following glycogenolysis, an induction of glycogen resynthesis is observed, resulting, within 9 hr, in glycogen levels that are 6-10 times higher than those measured before the application of either neurotransmitter. This effect of VIP or NA is concentration dependent and, for NA, is mediated by adrenergic receptors of the β subtype. The continued presence of the neurotransmitter is not necessary for this long-term effect, since pulses as short as 1 min result in the doubling of glycogen levels 9 hr later. The induction of glycogen resynthesis triggered by VIP or NA is dependent on protein synthesis, since both cycloheximide and actinomycin D abolish it entirely. The ability to elicit glycogenolysis is not sufficient per se to trigger the induction of glycogen resynthesis. Thus, two glycogenolytic agents such as methoxamine, an α1-adrenergic agonist, and phorbol 12, 13-dibutyrate, both acting via protein kinase C activation, are unable to induce glycogen resynthesis. This observation, taken together with the fact that dibutyryl- cAMP application also results in enhanced glycogen resynthesis, strongly suggests that the long-term effect of VIP or NA is mediated by the cAMP second-messenger pathway. These results indicate that the same neurotransmitter, for example, VIP or NA, can elicit two actions with different time courses: (1) glycogenolysis, occurring within minutes, and (2) glycogen resynthesis, fully expressed after several hours. The two actions are mechanistically coordinated since the long-term one, that is, glycogen resynthesis, ensures that sufficient substrate is available for the expression of the short-term effect, that is, glycogenolysis. These results also indicate that the glycogen content of astrocytes in primary culture, a condition in which neurons are absent, can increase considerably; a parallel could therefore be drawn with the marked increases in brain glycogen content, particularly in astrocytes, that are observed in experimental neurodegeneration induced by brain trauma or x-irradiation (Shimizu and Hamuro, 1958; Lundgren and Miquel, 1970). In both conditions, the increase in glycogen occurs in reactive astrocytes that have been partially or totally deprived of their neuronal environment.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Neuroscience|
|State||Published - Jan 1 1992|
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