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Low-carbohydrate and high-protein (LC-HP) diets are acceptable for improving physiological and metabolic parameters. However, the effects of LC-HP diets on the brain are unclear, which depend on glycometabolism for neuronal activity. Since astrocyte-neuron lactate shuttle (ANLS) is an essential pathway for maintaining brain functions, we investigated the changes in hippocampal memory function. In addition, the alteration of lactate transporter constituting ANLS and ANLS-related neurotrophic factors by feeding LC-HP diets was evaluated in healthy mice. C57BL/6 mice were divided into two groups: a group feeding LC-HP diet (24.6% carbohydrate, 57.6% protein, and 17.8% fat as percentages of calories) and a group feeding control diet (58.6% carbohydrate, 24.2% protein, and 17.2% fat as percentages of calories). Here, we found that 4 wk of LC-HP diet feeding suppressed memory function in mice evaluated by Y-maze. Hippocampal mRNA levels of lactate transporters, such as Mct1, Mct4, and Mct2, were unchanged with feeding LC-HP diets; however, LC-HP diets significantly decreased Dcx and Igf-1 receptor mRNA levels in the hippocampus. Bdnf and its related signaling in mice hippocampus exhibited no change by LC-HP diets. Although there was non-influence in the lactate-transport system, LC-HP diets would suppress hippocampal working memory with dysregulation of neuroplasticity. The current data propose the importance of food choices for maintaining hippocampal health.

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1.  This study was aimed to characterize gastrointestinal absorption of digoxin using wild-type (WT) and multidrug resistance protein 1a [mdr1a; P-glycoprotein (P-gp)] knockout (-/-) rats. 2.  In WT rats, the area under the plasma concentration-time curve (AUC) of oral digoxin increased after oral pretreatment with quinidine at 30 mg/kg compared with non-treatment, but the increasing ratio tended to decrease at a high dose of 100 mg/kg. In mdr1a (-/-) rats, however, quinidine pretreatment caused a dose-dependent decrease in the AUC. 3.  Quinidine pretreatment did not alter the hepatic availability of digoxin, indicating that the changes in the digoxin AUC were attributable to inhibition of the absorption process by quinidine; i.e. inhibition of influx by quinidine in mdr1a (-/-) rats and inhibition of efflux and influx by quinidine in WT rats. 4.  An in situ rat intestinal closed loop study using naringin implied that organic anion transporting peptide (Oatp) 1a5 may be a responsible transporter in the absorption of digoxin. 5.  These findings imply that the rat absorption behavior of digoxin is possibly governed by Oatp1a5-mediated influx and P-gp-mediated efflux. The mdr1a (-/-) rat is therefore a useful in vivo tool to investigate drug absorption associated with multiple transporters including P-gp.

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