Long-Term Effect of Porcine Brain Enzyme Hydrolysate Intake on Scopolamine-Induced Memory Impairment in Rats

Abstract

No study has revealed the effect of porcine brain enzyme hydrolysate (PBEH) on memory impairment. We aimed to examine the hypothesis that PBEH intake modulates memory deficits and cognitive behavior in scopolamine (SC)-induced amnesia rats, and its mechanism, including gut microbiota changes, was determined. Sprague–Dawley male rats had intraperitoneal injections of SC (2 mg/kg body weight/day) at 30 min after daily feeding of casein (MD-control), PBEH (7 mg total nitrogen/mL) at 0.053 mL (Low-PBEH), 0.159 mL (Medium-PBEH), 0.478 mL (High-PBEH), or 10 mg donepezil (Positive-control) per kilogram body weight per day through a feeding needle for six weeks. The Normal-control rats had casein feeding without SC injection. PBEH dose-dependently protected against memory deficits determined by passive avoidance test, Y-maze, water-maze, and novel object recognition test in SC-induced rats compared to the MD-control. The High-PBEH group had a similar memory function to the Positive-control group. Systemic insulin resistance determined by HOMA-IR was lower in the PBEH groups than in the Normal-control but not the Positive-control. In parallel with systemic insulin resistance, decreased cholesterol and increased glycogen contents in the hippocampus in the Medium-PBEH and High-PBEH represented reduced brain insulin resistance. PBEH intake prevented the increment of serum TNF-α and IL-1β concentrations in the SC-injected rats. Hippocampal lipid peroxide and TNF-α contents and mRNA TNF-α and IL-1β expression were dose-dependently reduced in PBEH and Positive-control. PBEH decreased the hippocampal acetylcholinesterase activity compared to the MD-control, but not as much as the Positive-control. PBEH intake increased the α-diversity of the gut microbiota compared to the MD-control, and the gut microbiota community was separated from MD-control. In metagenome function analysis, PBEH increased the energy metabolism-related pathways of the gut microbiota, including citric acid cycle, oxidative phosphorylation, glycolysis, and amino acid metabolism, which were lower in the MD-control than the Normal-control. In conclusion, alleviated memory deficit by PBEH was associated potentially with not only reducing acetylcholinesterase activity but also improving brain insulin resistance and neuroinflammation potentially through modulating gut microbiota. PBEH intake (1.5–4.5 mL of 7 mg total nitrogen/mL for human equivalent) can be a potential therapeutic agent for improving memory impairment.

Fecal Bacterial Community and Metagenome Function in Asians with Type 2 Diabetes, According to Enterotypes

“…The afferent, efferent, and enteric nervous systems are interconnected to respond to gut microbe signaling and together control various functions, including digestion and metabolism. Dramatic changes in diet and lifestyle, leading to obesity and T2DM, are linked to a disconnect between the altered gut microbiota and the PNS [ 26 , 27 ]. It is well-known that the autonomic nervous system modulates insulin secretion and plays an essential role in insulin resistance in T2DM [ 28 ].…”

“…The vagus nerve activates the cholinergic nervous system to promote an anti-inflammatory pathway and decreases intestinal permeability to modulate gut bacterial composition [ 27 , 33 ]. Gut microbiota in children and elderly persons are quite different from those in adults [ 34 ], which is related to the maturation and degeneration of the vagus nerve.…”

“…Infants have high levels of Bifidobacterium as beneficial bacteria and Clostridiaceae and Enterobacteriaceae as harmful bacteria, possibly linked to an immature vagus nerve system [ 34 ]. Scopolamine administration suppresses the parasympathetic nervous system in a rat model and induces gut dysbiosis by decreasing Bacteroides and Faecalibacterium prausnitzii and increasing Ruminococcus and Clostridium in the feces [ 27 ]. In the present study, the fecal bacteria of adults with and without T2DM were included as samples.…”

Mitigation of Memory Impairment with Fermented Fucoidan and λ-Carrageenan Supplementation through Modulating the Gut Microbiota and Their Metagenome Function in Hippocampal Amyloid-β Infused Rats

“…Propionate and butyrate among SCFAs improve brain insulin sensitivity through the gut-brain axis [ 13 ] and enhance parasympathetic dysfunction between the brain and the intestines. They contribute to cognitive function [ 14 ]. Dietary fiber also modulates the gut microbiota community to change bile acid reabsorption and metabolism, potentially influencing the host metabolism and brain function through the gut-brain axis [ 14 , 15 ].…”

“…They contribute to cognitive function [ 14 ]. Dietary fiber also modulates the gut microbiota community to change bile acid reabsorption and metabolism, potentially influencing the host metabolism and brain function through the gut-brain axis [ 14 , 15 ].…”