Neurotensin Regulates Proliferation and Stem Cell Function in the Small Intestine in a Nutrient-Dependent Manner.

Background & Aims: Intestinal stem cells (ISCs) are sensitive to dietary alterations and nutrient availability. Neurotensin (NT), a gut peptide localized predominantly to the small bowel and released by fat ingestion, stimulates the growth of intestinal mucosa under basal conditions and during periods of nutrient deprivation, suggesting a possible role for NT on ISC function.

Methods: Leucine-rich repeat-containing G-protein coupled receptor 5-Enhanced Green Fluorescent Protein (Lgr5-EGFP) NT wild type (Nt) and Lgr5-EGFP NT knockout (Nt) mice were fed ad libitum or fasted for 48 hours.

Absence of neurotensin attenuates intestinal dysbiosis and inflammation by maintaining Mmp7/α-defensin axis in diet-induced obese mice.

We previously reported that high levels of plasma neurotensin (NT), a gut hormone released from enteroendocrine cells of the small bowel, contribute to obesity and comorbid conditions. Gut microbiota has been implicated in the obesity development. Paneth cells are critical in maintaining gut microbiota composition and homeostasis by releasing antimicrobial proteins including α-defensins.

Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling.

Neurotensin is a peptide hormone released from enteroendocrine cells in the small intestine in response to fat ingestion. Although the mechanisms regulating neurotensin secretion are still incompletely understood, our recent findings implicate a role for extracellular signal-regulated kinase 1 and 2 as positive regulators of free fatty acid-stimulated neurotensin secretion. Previous studies have shown that kinase suppressor of Ras 1 acts as a molecular scaffold of the Raf/MEK/extracellular signal-regulated kinase 1 and 2 kinase cascade and regulates intensity and duration of extracellular signal-regulated kinase 1 and 2 signaling.

FFAR4 Is Involved in Regulation of Neurotensin Release From Neuroendocrine Cells and Male C57BL/6 Mice.

Neurotensin (NT), a 13 amino-acid peptide, is predominantly released from enteroendocrine cells of the small bowel in response to fat ingestion. Free fatty acid receptors (FFARs) FFAR1 and FFAR4 regulate secretion of gut hormones and insulin. Here, we show that docosahexaenoic acid, a long-chain fatty acid, has the most dramatic effect on NT release.

One-year double-blind study of the neurocognitive efficacy of olanzapine, risperidone, and haloperidol in schizophrenia.

Neurocognitive deficits in schizophrenia can reach 1 to 2 standard deviations below healthy controls. The comparative effect of typical and atypical antipsychotic medications on neurocognition is controversial, and based primarily on studies with small samples and large doses of typical comparator medications. The present study assessed neurocognitive efficacy.

Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis.

Background: Neurocognitive deficits are severe in first-episode psychosis.

Methods: Patients (N = 263) with first-episode psychosis (schizophrenia, schizoaffective, or schizophreniform disorders) were randomly assigned to double-blind treatment with olanzapine (mean 11.30 mg/day) or haloperidol (mean 4.

Psychological processes underlying risky decisions in drug abusers.

Decision-making deficits are considered to be a significant contributing factor for drug abuse. Drug abusers performed poorly on a simulated gambling task (A. Bechara, H.

Periadolescent rats (P41-50) exhibit increased susceptibility to D-methamphetamine-induced long-term spatial and sequential learning deficits compared to juvenile (P21-30 or P31-40) or adult rats (P51-60).

We have previously shown that P11-20 treatment with d-methamphetamine (MA) induces impaired spatial navigation in the Morris water maze (MWM), whereas P1-10 treatment does not. Little is known about the long-term behavioral consequences of MA during juvenile, adolescent, and early adult brain development. In dose-response experiments, we tested successive 10-day intervals of exposure to MA in rats (P21-30, P31-40, P41-50, and P51-60; four doses per day).

Developmental 3,4-methylenedioxymethamphetamine (MDMA) impairs sequential and spatial but not cued learning independent of growth, litter effects or injection stress.

Previously, we have shown that rats administered MDMA from postnatal (P) days 11-20 had reductions in body weight during the period of treatment and as adults they had deficits in sequential and spatial learning and memory. In the present study, to control for weight reductions, we used litters with double the number of offspring to induce growth restriction comparable to that of standard size litters treated with MDMA. Litters were treated twice daily from P11 to 20 with vehicle or MDMA (20 mg/kg) or only weighed.