**5. Mechanisms of glucose effect on memory**

receptor subunit systems; metabolic signaling pathways; LTP/LTD (long-term potentiation/ long-term depression); genetic and epigenetic modifications. (Memory retrieval might involve the same systems and processes, but with different mechanisms). Both memory formation and retrieval involve other brain functions, including attention. The systems and processes earlier stated are affected by cerebral glucose, which can serve as a substrate or produce intermediate substrates for some stages of their syntheses. The cerebral glucose content is dependent on the plasma glucose, both of which are under constant regulation by the brain (hypothalamus), some internal organs (liver, kidney). The blood glucose is constantly regulated, also by the effect of the neuro-endocrine control on the gastrointesti‐ nal tract, organs (such as the liver and kidney), as well as the effect of the hypothalamus on these organs. The processes that are regulated in these organs by the higher regulato‐ ry centres (e.g. hypothalamus) are food intake, gluconeogenesis, glycogenolysis, glucose cycling – to ensure normal glycemic allostasis. These higher control centres, and the memory function are under constant pressure from modulating factors such as exogenous (e.g. environmental, ethanol), endogenous (ethanol, some physiological indices) – might affect the resultant effect of glucose on memory function. Alcohol actions [42-45] as represented on the model are one of a bi-directional effect of summation, meaning that alcohol affects memory, as well as glucose regulatory systems. The receptor systems of the brain could be modulated by both alcohol and glucose [46, 47]. Alcohol is a psychotic substance in widespread usage in the world. Importantly, this substance is also produced in vivo during biochemical reactions in an organism (including humans). In certain circumstances (varying physiological state, for instance during pregnancy, disease states), the level of endoge‐ nous ethanol produced significantly increases. This increase might have a protective effect, but the reason or mechanism on the general role of the increase in endogenous concentra‐ tion ethanol is not fully known. Ethanol affects some neurotransmitters and receptor systems. Ethanol acts on ionotropic, metabotropic G-protein receptor, potassium ion channels [48-50]. Ethanol acts on metabotropic receptors of mGluR5, mGluR2/3, mGluR1 [51-53]. These metabotropic receptors (mGluR3 of the prefrontal cortex) have been also implicated in cognitive disorders in especially alcoholics [54]. mGluR5 and mGluR1 receptors have been recently implicated in cognition [53]. Ethanol causes hypoglycemia [43, 55]. Besides, it is reported that alcohol causes disorders in the expression of several genes,

116 Glucose Homeostasis

although the mechanisms remain not quite clear [56].

Glucose plays a pivotal role in memory and might enhance LTP/LTD [57] as hypoglycemia is associated with deficits in memory, and learning [58, 59]. Apart from producing ATP for neural energy, other substances may be synthesized from glucose that affects neuronal activity and functions (including memory) [60-62]. For example, it is known that d-serine (maybe synthe‐ sized from glucose molecule) affects LTP, synaptic plasticity, enhance information retrieval [60-64]. Hypoglycemia is associated with both d-serine and NO release aimed at enhancing LTP [58]. These substances can also regulate neuronal transcription factors [65]. A vast number of these signaling pathways, neurotransmitter and receptor systems, and are dependent on the activity level of neurons, and activity dependent transcriptions – activators and suppressor [66, 67]. Other brain cells (especially astrocytes) can modulate neuronal activity through

While several studies have noted that glucose is a critical factor for memory function, what is not exactly clear is whether the effect is a direct or indirect one. In this section, we shall be mainly concerned with the mechanisms and processes of how glucose affects memory. Pertinent literature and latest developments in the field will be reviewed. It will be necessary to have in mind that memory function (formation and retrieval of neural data) is overlapped or is connected with other brain functions such as perception, attention etc. Therefore, glucose is a vital regulating factor for other brain functions. We shall consider the various views, concepts and models of how glucose affects memory function, and provide a comprehensive model of glucose memory facilitation effect (Figure 1).
