Synaptic energy metabolism and neuronal excitability, in sickness and health

Abstract

Most of the energy produced in the brain is dedicated to supporting synaptic transmission. Glucose is the main fuel, providing energy and carbon skeletons to the cells that execute and support synaptic function: neurons and astrocytes, respectively. It is unclear, however, how glucose is provided to and used by these cells under different levels of synaptic activity. It is even more unclear how diseases that impair glucose uptake and oxidation in the brain alter metabolism in neurons and astrocytes, disrupt synaptic activity, and cause neurological dysfunction, of which seizures are one of the most common clinical manifestations. Poor mechanistic understanding of diseases involving synaptic energy metabolism has prevented the expansion of therapeutic options, which, in most cases, are limited to symptomatic treatments. To shed light on the intersections between metabolism, synaptic transmission, and neuronal excitability, we briefly review current knowledge of compartmentalized metabolism in neurons and astrocytes, the biochemical pathways that fuel synaptic transmission at resting and active states, and the mechanisms by which disorders of brain glucose metabolism disrupt neuronal excitability and synaptic function and cause neurological disease in the form of epilepsy.

How Do Cognitively Stimulating Activities Affect Cognition and the Brain Throughout Life?

“…Education and cognitive activity involve novelty, cognitive effort, and motivation-all of which activate the locus ceruleus, which serves as the brain's arousal hub region (Mather, in press) and focuses attention and working memory in the moment (Mather, Clewett, Sakaki, & Harley, 2016) while also enhancing the likelihood of synaptic changes (Inoue et al, 2013;Maity, Rah, Sonenberg, Gkogkas, & Nguyen, 2015;Palacios-Filardo & Mellor, 2019;Salgado, Kohr, & Trevino, 2012;Salgado, Treviño, & Atzori, 2016). But the synaptic activity involved in this enhanced attentional focus and that is required for synaptic change also has a metabolic cost (Holroyd, 2016;Oyarzabal & Marin-Valencia, 2019). Synaptic activity creates amyloid-β as well as other metabolic waste (Cirrito et al, 2005).…”

Proteomic Analysis of Mucopolysaccharidosis IIIB Mouse Brain

“…Energy metabolism is relevant for neuronal plasticity, axonal transport, synaptic vesicle trafficking and docking, and thereby neurotransmitter release [72]. In our study, dysregulation of the expression levels of proteins involved in "Synaptic vesicle trafficking" and in "neurotransmitter release" pathways, including the syntaxin-binding protein 1 (Stxbp1), synapsin 1 and 2 (Syn1, Syn2), and Rab3a, was observed in the brain of MPS IIIB mice.…”

Determining bioenergy field of autistic and normal healthy children: an electrophotonic imaging study

“…40 The synaptic energy support cell metabolism and cell function that is associated with health and disease. 41 The energy level of the pancreas, liver and coronary vessels showed a significant difference between autistic and healthy children. These outcomes can be possibly correlate with other psychological scales of autism in future studies.…”