Type 2 diabetes mellitus in the pathophysiology of Alzheimer's disease.

Both Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) are two common forms of disease worldwide and many studies indicate that people with diabetes, especially DM, are at higher risk of developing AD. AD is characterized by progressive cognitive decline and accumulation of ß-amyloid (Aß) forming senile plaques. DM is a metabolic disorder characterized by hyperglycemia in the context of insulin resistance and relative lack of insulin. Both diseases also share common characteristics such as loss of cognitive function and inflammation. Inflammation resulting from Aß further induces production of Aß1-42 peptides. Inflammation due to overnutrition induces insulin resistance and consequently DM. Memory deficit and a decrease in GLUT4 and hippocampal insulin signaling have been observed in animal models of insulin resistance. The objective of this review was to show the shared characteristics of AD and DM.

Tanto a doença de Alzheimer (DA) e diabetes mellitus tipo 2 (DM2) são duas formas comuns de doenças no mundo e muitos estudos indicam que pessoas com diabetes, especialmente DM2, estão em maior risco de desenvolver DA. DA é caracterizada por um declínio cognitivo progressivo e acúmulo de ß-amilóide (Aß) formando placas senis. A DM2 é um distúrbio metabólico caracterizado por hiperglicemia no âmbito da resistência à insulina e falta relativa de insulina. Ambas as doenças também compartilham características comuns tais como a perda da função cognitiva e inflamação. A inflamação resultante de Aß induz ainda mais a produção de peptídeos Aß1-42. A inflamação devido à hipernutrição induz resistência a insulina e consequentemente T2D. Um deficit de memória e uma diminuição de sinalização de insulina hipocampal e GLUT4 foram observados em modelos animais de resistência a insulina. O objetivo desta revisão é mostrar as características comuns das DA e DM2.

Feeding behaviour after injection of α-adrenergic receptor agonists into the median raphe nucleus of food-deprived rats.

This study investigated the participation of median raphe nucleus (MnR) α1-adrenergic receptors in the control of feeding behaviour. The α1-adrenergic agonist phenylephrine (PHE) and α2-adrenergic agonist clonidine (CLON) (at equimolar doses of 0, 6 and 20 nmol) were injected into the MnR of: a) rats submitted to overnight fasting (18 h); or b) rats maintained with 15 g of lab chow/day for 7 days. Immediately after the drug injections, the animals were placed in the feeding chamber and feeding and non-ingestive behaviours such as grooming, rearing, resting, sniffing and locomotion were recorded for 30 min. The results showed that both doses of PHE injected into the MnR of overnight fasted animals decreased food intake accompanied by an increase in the latency to start feeding. A reduction in feeding duration was observed only after treatment of the MnR with the 20 nmol dose of PHE. Both locomotion duration and sniffing frequency increased after injection with the highest dose PHE into the MnR. Feeding frequency and the other non-ingestive behaviours remained unchanged after PHE treatment in the MnR. Both doses of PHE injected into the MnR of food-restricted rats decreased food intake. This hypophagic response was accompanied by a decrease in feeding duration only after treatment of the MnR with the highest dose of PHE. The latency to start feeding and feeding frequency were not affected by injection of either dose of PHE into the MnR. While both doses of PHE increased sniffing duration, the highest dose of PHE increased resting duration and resting frequency. Treatment with CLON into the MnR did not affect feeding behaviour in either of the food deprivation conditions. The present results indicate the inhibitory functional role of α1-adrenergic receptors within the MnR on feeding behaviour.

The microinjection of AMPA receptor antagonist into the accumbens shell failed to change food intake, but reduced fear-motivated behaviour in free-feeding female rats.

This study investigated the effect of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 2.5 and 5.0 nmol/side) microinjected into the core and shell sub-regions of the accumbens (Acb) nucleus, on food intake and the level of anxiety in female rats. Bilateral microinjections of CNQX (5.0 nmol/side) into the Acb shell (AP, +1.08 to +2.04), but not into the Acb core, induced an anxiolytic-like effect in relation to rats microinjected with vehicle, since the animals exhibited low level of SAP in the feeding test. The anxiolytic-like effect induced by 5.0 nmol CNQX microinjection into the Acb shell may not be ascribed to changes in the motor activity of the animals, because the frequency of locomotion, rearing and grooming remained unchanged after the drug microinjection. However, neither Acb shell nor Acb core CNQX microinjections were able to change the animals food intake along 1h feeding behaviour evaluation. Food intake remained unchanged 24h after the drug microinjections either into the Acb shell or into the Acb core. The data suggest that AMPA receptor blockade in the Acb nucleus may differentially change the ingestive and defensive behaviours in female rats.