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Nutrient limitation affects presynaptic structures through dissociable Bassoon autophagic degradation and impaired vesicle release.


ABSTRACT: Acute mismatch between metabolic requirements of neurons and nutrients/growth factors availability characterizes several neurological conditions such as traumatic brain injury, stroke and hypoglycemia. Although the effects of this mismatch have been investigated at cell biological level, the effects on synaptic structure and function are less clear. Since synaptic activity is the most energy-demanding neuronal function and it is directly linked to neuronal networks functionality, we have explored whether nutrient limitation (NL) affects the ultrastructure, function and composition of pre and postsynaptic terminals. We show that upon NL, presynaptic terminals show disorganized vesicle pools and reduced levels of the active zone protein Bassoon (but not of Piccolo). Moreover, NL triggers an impaired vesicle release, which is reversed by re-administration of glucose but not by the blockade of autophagic or proteasomal protein degradation. This reveals a dissociable correlation between presynaptic architecture and vesicle release, since restoring vesicle fusion does not necessarily depend from the rescue of Bassoon levels. Thus, our data show that the presynaptic compartment is highly sensitive to NL and the rescue of presynaptic function requires re-establishment of the metabolic supply rather than preventing local protein degradation.

SUBMITTER: Catanese A 

PROVIDER: S-EPMC6259322 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Nutrient limitation affects presynaptic structures through dissociable Bassoon autophagic degradation and impaired vesicle release.

Catanese Alberto A   Garrido Débora D   Walther Paul P   Roselli Francesco F   Boeckers Tobias M TM  

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20180704 11


Acute mismatch between metabolic requirements of neurons and nutrients/growth factors availability characterizes several neurological conditions such as traumatic brain injury, stroke and hypoglycemia. Although the effects of this mismatch have been investigated at cell biological level, the effects on synaptic structure and function are less clear. Since synaptic activity is the most energy-demanding neuronal function and it is directly linked to neuronal networks functionality, we have explore  ...[more]

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