Effects of Smart Drugs on Cholinergic System and Non-Neuronal Acetylcholine in the Mouse Hippocampus: Histopathological Approach

Abstract

In recent years, people in the United States and other countries have been using smart drugs, called nootropic or cognitive enhancers, to improve concentration and memory learning skills. However, these drugs were originally prescribed for attention-deficit hyperactivity disorder and dementia, and their efficacy in healthy people has not yet been established. We focused on acetylcholine in the hippocampus, which is responsible for memory learning, and elucidate the long-term effects of smart drugs on the neural circuits. Smart drugs were administered orally in normal young mice for seven weeks. The hippocampus was sectioned and compared histologically by hematoxylin and eosin (HE) staining, immunohistochemistry for acetylcholine, and immunoelectron microscopy. There were no significant changes in acetylcholinesterase staining. However, in HE, we found perivascular edema, and choline acetyltransferase staining showed increased staining throughout the hippocampus and new signal induction in the perivascular area in the CA3, especially in the aniracetam and α-glyceryl phosphoryl choline group. Additionally, new muscarinic acetylcholine receptor signals were observed in the CA1 due to smart drug intake, suggesting that vasodilation might cause neuronal activation by increasing the influx of nutrients and oxygen. Moreover, these results suggest a possible new mechanism of acetylcholine-mediated neural circuit activation by smart drug intake.

Anti-Obesity and Anti-Inflammatory Synergistic Effects of Green Tea Catechins and Citrus β-Cryptoxanthin Ingestion in Obese Mice

“…Green tea components and/or β-cryptoxanthin was administered by free drinking [ 38 , 77 ] for 4 weeks from week 11 to week 15 ( Table 4 ). The green tea catechin mix (Sigma-Aldrich Japan, Tokyo, Japan) was dissolved in water and administered (1.7 mg/kg) daily at half the concentration that showed efficacy in humans (200 mg/60 kg ideal human body weight) [ 30 , 31 ].…”

Combined Ingestion of Tea Catechin and Citrus β-Cryptoxanthin Improves Liver Function via Adipokines in Chronic Obesity

“…In accordance with previous studies [29,31,32], green tea catechins and/or β-cryptoxanthin were orally administered for 4 weeks, from 11 to 15 weeks of age. Green tea catechin (Sigma-Aldrich Japan, Tokyo, Japan) was diluted in water and administered daily at a dose of 1.7 mg/kg, which is equivalent to half the concentration effective in humans (200 mg/60 kg) [33,34].…”

Severe Acute Liver Dysfunction Induces Delayed Hepatocyte Swelling and Cytoplasmic Vacuolization, and Delayed Cortical Neuronal Cell Death

“…Tissue preparation for histochemistry and electron microscopy was performed as previously described [ 65 , 66 , 67 , 68 ].…”