Age-dependent increase in apoptosis is associated with dysregulation of miR-92a/Akt/mTOR and NF-κB signaling pathways in male rats.

Brain aging is the leading risk factor for most neurodegenerative diseases and has been linked with high rates of neuron loss. Thus, identifying molecular mechanisms underlying neuron loss and pharmacological modulation may be of great importance for slowing or preventing age-related diseases. Herein, we investigated the roles of miR-92a, Akt, mTOR, and NF-κB in age-associated apoptosis in the hippocampus (a critical structure involved in brain aging) of male rats alone and in combination with prazosin.

Involvement of γ-Aminobutyric Acid and N-methyl-D-aspartate Receptors in Diabetic Gastropathy in Rats: Possible Beneficial Effect of Prolonged Treatment with Insulin and Magnesium Supplement.

Gastrointestinal dysfunction is a severe and common complication in diabetic patients. Some evidence shows that gamma-aminobutyric acid (GABA) and glutamate contribute to diabetic gastrointestinal abnormalities. Therefore, we examined the impact of prolonged treatment with insulin and magnesium supplements on the expression pattern of GABA type A (GABA-A), GABA-B, and N-methyl-D-aspartate (NMDA) glutamate receptors as well as nitric oxide synthase 1 (NOS-1) in the stomach of type 2 diabetic rats.

Long-term GABA Supplementation Regulates Diabetic Gastroenteropathy through GABA Receptor/trypsin-1/PARs/Akt/COX-2 Axis.

Aim: Molecular alterations of diabetic gastroenteropathy are poorly identified. This study investigates the effects of prolonged GABA supplementation on key protein expression levels of trypsin-1, PAR-1, PAR-2, PAR-3, PI3K, Akt, COX-2, GABAA, and GABAB receptors in the gastric tissue of type 2 diabetic rats (T2DM).

Method: To induce T2DM, a 3-month high-fat diet and 35 mg/kg of streptozotocin was used.

Protective potential of naringenin and its nanoformulations in redox mechanisms of injury and disease.

Increasing evidence suggests that elevated intracellular levels of reactive oxygen species (ROS) play a significant role in the pathogenesis of many diseases. Increased intracellular levels of ROS can lead to the oxidation of lipids, DNA, and proteins, contributing to cellular damage. Hence, the maintenance of redox hemostasis is essential.

Motor Dysfunction of Gastric Antral Smooth Muscle in Diabetic Rats: Contribution of ATP-Dependent Potassium Channels.

Background: The goal of the current research was to further elucidate the role of adenosine triphosphate (ATP)-sensitive potassium (K) channels in the motility and contractility force of gastric smooth muscle of diabetic rats.

Materials And Methods: Male Wistar rats (190-230 g) were grouped into control and streptozotocin (STZ)-induced diabetes (55 mg/kg) rats. Thirty days later, gastric muscle contractility was measured using a myograph and a force transducer of antral segments immersed in a tissue bath.

Alterations in expression of α1-adrenergic receptors possibly are involved in prevention of age-associated apoptosis in rat hippocampus by treadmill exercise.

Objectives: Exercise is assumed to attenuate age-related neuronal apoptosis, but the detailed mechanism(s) is not fully understood. α1-Adrenergic receptors (ARs) can either trigger or suppress apoptosis, therefore, here we determined the impact of treadmill exercise on the expression of the apoptosis regulatory proteins as well as α1-AR subtypes α1A- and α1B-ARs, in order to elucidate a possible association between apoptosis and the hippocampal expression of α1-ARs in aged male rats.

Methods: Twenty-one male Wistar rats were divided into 3 groups (n=7): young control, aged sedentary, and aged + exercise.

Changes in Protease-Activated Receptor and Trypsin-1 Expression Are Involved in the Therapeutic Effect of Mg Supplementation in Type 2 Diabetes-Induced Gastric Injury in Male Adult Rats.

Purpose: Gastric inflammation is common and usually severe in patients with type 2 diabetes mellitus (T2DM). Evidence suggests protease-activated receptors (PARs) are a link between inflammation and gastrointestinal dysfunction. Given that magnesium (Mg) deficiency is a highly prevalent condition in T2DM patients, we assessed the therapeutic role of Mg on the factors involved in gastric inflammation in T2DM.

Alleviation of cholestatic liver injury and intestinal permeability by lubiprostone treatment in bile duct ligated rats: role of intestinal FXR and tight junction proteins claudin-1, claudin-2, and occludin.

Gut barrier disintegrity and endotoxin translocation to the liver and systemic circulation are serious clinical complications associated with the stoppage of intestinal bile flow. There is no precise pharmacological option to prevent increased intestinal permeability after bile duct ligation (BDL). Lubiprostone, a chloride channel-2 agonist, has been shown to accelerate restoration of epithelial barrier dysfunction caused by injury, but the exact mechanisms underlying the beneficial effects of lubiprostone on intestine barrier integrity remain unknown.

Exercise may alleviate age-related spatial memory impairment by rescuing β-adrenergic receptor dysregulation via both G protein-dependent and β-arrestin-dependent mechanisms in rat hippocampus.

Hippocampal-dependent memory abilities including spatial memory decline with age. Exercise improves memory decline in aging brain, but, the precise mechanisms are still unknown. Learning and memory are recently hypothesized to be mediated by a β-arrestin (βArr)-dependent β-adrenergic pathway.

Anxiety and hippocampal neuronal activity: Relationship and potential mechanisms.

The hippocampus has been implicated in modulating anxiety. It interacts with a variety of brain regions, both cortical and subcortical areas regulating emotion and stress responses, including prefrontal cortex, amygdala, hypothalamus, and the nucleus accumbens, to adjust anxiety levels in response to a variety of stressful conditions. Growing evidence indicates that anxiety is associated with increased neuronal excitability in the hippocampus, and alterations in local regulation of hippocampal excitability have been suggested to underlie behavioral disruptions characteristic of certain anxiety disorders.

Prenatal stress and increased susceptibility to anxiety-like behaviors: role of neuroinflammation and balance between GABAergic and glutamatergic transmission.

Neuroplasticity during the prenatal period allows neurons to regenerate anatomically and functionally for re-programming the brain development. During this critical period of fetal programming, the fetus phenotype can change in accordance with environmental stimuli such as stress exposure. Prenatal stress (PS) can exert important effects on brain development and result in permanent alterations with long-lasting consequences on the physiology and behavior of the offspring later in life.

Possible involvement of the dopamine D2 receptors of ventromedial hypothalamus in the control of free- and scheduled-feeding and plasma ghrelin level in rat.

Objectives: We investigated effect of the ventromedial hypothalamus (VMH) dopamine D2 receptor inhibition on food intake and plasma ghrelin following chronic free or scheduled meal with different caloric intakes.

Methods: Male Wistar rats (220-250 g) were fed diets containing free (control) or three scheduled diets of standard, restricted and high-fat for 1 month. The animals stereotaxically received an intra VMH single dose of sulpiride (0.

Developmental effects of early-life stress on dopamine D2 receptor and proteins involved in noncanonical D2 dopamine receptor signaling pathway in the prefrontal cortex of male rats.

Objectives: Dopamine neurotransmission is implicated in multiple neuropsychiatric disorders, most strikingly in Parkinson's disease, bipolar disorder, attention-deficit hyperactivity disorder and schizophrenia. In addition to canonical pathway, D2-receptor (D2R) exerts some of its biological actions through regulating the activity of Akt and GSK3, which in turn were found to be altered in several psychiatric illnesses. The present study examined the impacts of maternal separation, an early-life stress model which has been associated with disturbed neurodevelopment and appearance of many psychiatric disorders, on developmental changes in dopamine concentration and the expression of D2Rs, Akt and GSK-3β in the medial prefrontal cortex (PFC; a key target of stress) in adolescent and young adult male rats.

Vitamin C protects against chronic social isolation stress-induced weight gain and depressive-like behavior in adult male rats.

Considering the importance of ghrelin in stress-induced hyperphagia and a role of antioxidants in decreasing body weight, in the present study, the effect of vitamin C (VitC) on ghrelin secretion and food intake following chronic social isolation (CIS) was evaluated in rats. Thirty two male Wistar rats (200-220g) were randomly divided into: control, VitC, CIS, and CIS + VitC groups. Animals received VitC (500 mg/kg/day)/saline by gavage for 3 weeks.

Long-Term Decreases in the Expression of Calcineurin and GABAA Receptors Induced by Early Maternal Separation Are Associated with Increased Anxiety-Like Behavior in Adult Male Rats.

Introduction: Early life stress is a well-described risk factor of anxiety disorders in adulthood. Dysfunction in GABA/glutamate receptors and their functional regulator, calcineurin, is linked to anxiety disorders. Here, we investigated the effect of early life stress, such as repeated maternal separation (MS; 3 h per day from postnatal day [P] 2 to 11), on changes in the expression of calcineurin as well as the ionotropic glutamatergic and GABAergic receptors including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and GABAA receptors in the hippocampus and prefrontal cortex (PFC) of adolescent (P35) and adult (P62) male Wistar rats and their correlations with anxiety-like behavior in adulthood.

Honey protects against chronic unpredictable mild stress induced- intestinal barrier disintegration and hepatic inflammation.

Chronic stress is linked to liver injury by increasing intestinal permeability to lipopolysaccharide (LPS), which in turn can result in systemic and liver inflammation and damage. Beneficial effect of honey in the prevention of liver injury has been shown in previous studies, but mechanisms underlying are still less known. Here, we examined the therapeutic impacts of honey on intestinal nuclear factor-κB (NF-κB; an important regulator of stress-induced immune and inflammatory responses) and ileal tight junction (TJ) proteins of claudin-1 and ZO-1, serum LPS, liver inflammation and oxidative markers of malondialdehyde (MDA), nitric oxide (NO), (erythroid-derived 2)-like 2 (Nrf2), tumor necrosis factor (TNF)-α and total antioxidant capacity (TAC) following chronic unpredictable mild stress (CUMS) using Western blotting, ELISA kit and spectrophotometry.

Negative relationship between brain α-AR neurotransmission and βArr2 levels in anxious adolescent rats subjected to early life stress.

Early-life stress is correlated with the development of anxiety-related behavior in adolescence, but underlying mechanisms remain poorly known. The α-adrenergic receptor (AR) is linked to mood regulation and its function is assumed to be regulated by β-arrestins (βArrs) via desensitization and downregulation. Here, we investigated correlation between changes in α-AR and βArr2 levels in the prefrontal cortex (PFC) and hippocampus of adolescent and adult male rats subjected to maternal separation (MS) and their relationship with anxiety-like behavior in adolescence.

Norepinephrine, neurodevelopment and behavior.

Neurotransmitters play critical roles in the developing nervous system. Among the neurotransmitters, norepinephrine (NE) is in particular postulated to be an important regulator of brain development. NE is expressed during early stages of development and is known to regulate both the development of noradrenergic neurons and the development of target areas.

Mechanisms underlying anticonvulsant and proconvulsant actions of norepinephrine.

Norepinephrine (NE) has been shown to exert a potent suppressant effect on seizure development. On the other hand, several lines of evidence have shown that increased NE level is proconvulsant under certain conditions. These data suggest that variations in NE levels could affect modulatory action of noradrenergic system on seizures.

Epilepsy-associated alterations in hippocampal excitability.

The hippocampus exhibits a wide range of epilepsy-related abnormalities and is situated in the mesial temporal lobe, where limbic seizures begin. These abnormalities could affect membrane excitability and lead to overstimulation of neurons. Multiple overlapping processes refer to neural homeostatic responses develop in neurons that work together to restore neuronal firing rates to control levels.

Decrease of high voltage Ca currents in the dentate gyrus granule cells by entorhinal amyloidopathy is reversed by calcium channel blockade.

In the Alzheimer's disease (AD), entorhinal-hippocampal circuit is one of the earliest affected networks. There are some evidences indicating abnormal neuronal excitability and impaired synaptic plasticity in the dentate gyrus (DG) of AD animal model. However, the underlying mechanism leading to DG dysfunction particularly in the early phase of AD is not known.

Calcium channel blockade attenuates abnormal synaptic transmission in the dentate gyrus elicited by entorhinal amyloidopathy.

Entorhinal-hippocampal network is one of the earliest circuits which is affected by Alzheimer's disease (AD). There are numerous data providing the evidence of synaptic deficit in the dentate gyrus (DG) of AD animal model. However, there is little known about how entorhinal cortex (EC) amyloidophaty affects each excitatory and/or inhibitory transmission in the early stage of AD.

Chronic administration of ghrelin regulates plasma glucose and normalizes insulin levels following fasting hyperglycemia and hyperinsulinemia.

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor. The majority of the previous studies have shown that the short-term ghrelin treatment induces hyperglycemia and hypoinsulinemia in healthy humans and rodents. However, the results obtained from long-term treatment with ghrelin are not clear enough.