Protective potential of glucagon like peptide 2 (GLP-2) against the neurodegeneration

Neurodegeneration consists in loss of neuron specific types, pattern and distribution, leading to progressive dysfunctions of the central nervous system. Neurodegenerative diseases include diverse pathological conditions, among which Alzheimer’s and Parkinson’s diseases are the most prevalent ones. Alzheimer’s disease is known as a growing dementia, characterized by progressive language, memory, and cognitive loss, while Parkinson’s disease is primarily characterized as a motor disorder. Senile plaques, caused by amyloid β peptide, hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of Alzheimer’s disease. Amyloid β oligomer formation is associated with development of reactive oxygen and nitrogen species, inflammation, calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions related with learning and memory. Parkinson’s disease is produced by dopaminergic neuron deterioration in the extrapyramidal tract of the midbrain. Accumulation of α-synuclein proteins (Lewy bodies) in the central, autonomic, and peripheral nervous system is the hallmark of the Parkinson’s disease. The Levy bodies break the neuronal membrane leading to neuronal death through oxidative stress, excitotoxicity, energy failure and neuroinflammation

Natural Compounds as Beneficial Antioxidant Agents in Neurodegenerative Disorders: A Focus on Alzheimer’s Disease

The positive role of nutrition in chronic neurodegenerative diseases (NDs) suggests that dietary interventions represent helpful tools for preventing NDs. In particular, diets enriched with natural compounds have become an increasingly attractive, non-invasive, and inexpensive option to support a healthy brain and to potentially treat NDs. Bioactive compounds found in vegetables or microalgae possess special properties able to counteract oxidative stress, which is involved as a triggering factor in neurodegeneration. Here, we briefly review the relevant experimental data on curcuminoids, silymarin, chlorogenic acid, and compounds derived from the microalga Aphanizomenon flos aquae (AFA) which have been demonstrated to possess encouraging beneficial eects on neurodegeneration, in particular on Alzheimer’s disease models

Gastric emptying, small intestinal transit and fecal output in dystrophic (mdx) mice

Duchenne muscular dystrophy (DMD), which results from deficiency in dystrophin, a sarcolemma protein of skeletal, cardiac and smooth muscle, is characterized by progressive striated muscle degeneration, but various gastrointestinal clinical manifestations have been observed. The aim was to evaluate the possible impact of the dystrophin loss on the gastrointestinal propulsion in mdx mice (animal model for DMD). The gastric emptying of a carboxymethyl cellulose/phenol red dye non-nutrient meal was not significantly different at 20 min from gavaging between wild-type and mdx mice. The intestinal transit and the fecal output were significantly decreased in mdx versus normal animals, although the length of the intestine was similar in both animals. The present results provide evidence for motor intestinal alterations in mdx mice in in vivo conditions

Indicaxanthin from Opuntia ficus-indica fruit ameliorates glucose dysmetabolism and counteracts insulin resistance in high-fat-diet-fed mice

Obesity-related dysmetabolic conditions are amongst the most common causes of death globally. Indicaxanthin, a bioavailable betalain pigment from Opuntia ficus-indica fruit, has been demonstrated to modulate redox-dependent signalling pathways, exerting significant anti-oxidative and anti-inflammatory effects in vitro and in vivo. In light of the strict interconnections between in-flammation, oxidative stress and insulin resistance (IR), a nutritionally relevant dose of indicaxanthin has been evaluated in a high-fat diet (HFD) model of obesity-related IR. To this end, biochemical and histological analysis, oxidative stress and inflammation evaluations in liver and adipose tissue were carried out. Our results showed that indicaxanthin treatment significantly reduced body weight, daily food intake and visceral fat mass. Moreover, indicaxanthin administration induced remark-able, beneficial effects on HFD-induced glucose dysmetabolism, reducing fasting glycaemia and insulinaemia, improving glucose and insulin tolerance and restoring the HOMA index to physiological values. These effects were associated with a reduction in hepatic and adipose tissue oxidative stress and inflammation. A decrease in RONS, malondialdehyde and NO levels, in TNF-α, CCL-2 and F4-80 gene expression, in p65, p-JNK, COX-2 and i-NOS protein levels, in crown-like structures and hepatic inflammatory foci was, indeed, observed. The current findings encourage further clinical studies to confirm the effectiveness of indicaxanthin to prevent and treat obesity-related dysmetabolic conditions

Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility.

The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin® is an AFA extract particularly rich in -PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if -PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a -PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a traceamine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin® and exogenous -PEA, suggesting a trace-amine involvement in the Klamin® effects. Accordingly, AphaMax®, an AFA extract containing lesser amount of -PEA, failed to modify colon contractility. Moreover, the Klamin® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin® exerts spasmolytic effects in human colon contractility through -PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus

Signal transduction pathways involved in the mechanical responses to protease-activated receptors in rat colon

ABSTRACT Recording simultaneously in vitro the changes of endoluminal pressure (index of circular muscle activity) and isometric tension (index of longitudinal muscle activity), we examined the mechanisms responsible for the apamin-sensitive relaxant and contractile responses induced by protease-activated receptor (PAR)-1 and PAR-2 activating peptides, SFLLRN-NH 2 and SLIGRL-NH 2 , respectively, in rat colon. In the circular muscle, the inhibitory effects of SFLLRN-NH 2 and SLIGRL-NH 2 were significantly reduced by ryanodine, an inhibitor of Ca 2ϩ release from the sarcoplasmic reticulum, but unaffected by 1- , a protein kinase C (PKC) inhibitor, or genistein, a tyrosine kinase inhibitor. In the longitudinal muscle, the contractile responses to SFLLRN-NH 2 and SLIGRL-NH 2 were significantly reduced by nifedipine, an L-type calcium channel blocker, ryanodine, GF109203X, genistein, and abolished by U73122. The effects of genistein were additive with GF109203X but not with nifedipine. In the longitudinal muscle, the relaxant responses to the highest concentrations of SFLLRN-NH 2 and SLIGRL-NH 2 were abolished by nifedipine, reduced by genistein, and unaffected by ryanodine or GF109203X. In conclusion, influx of extracellular Ca 2ϩ through L-type voltage-dependent channels or release of Ca 2ϩ from intracellular stores are determining for the opening of the apamin-sensitive K ϩ channels responsible for longitudinal muscle relaxation or circular muscle inhibitory response, respectively, in rat colon. The longitudinal muscle contraction is mediated by activation of PLC; PKC and tyrosine kinase are involved in the cascade process, playing a parallel role. Indeed, tyrosine kinase and L-type Ca 2ϩ channels would act sequentially

Takayasu's disease effects on the kidneys: current perspectives

Takayasu arteritis (TA) is a chronic vasculitis disease of unknown etiology. Clinically significant renal disease is relatively common, and renovascular hypertension is the major renal problem. The assessment of TA activity is usually challenging because vascular inflammation may progress to fixed vascular injury without findings of active disease. Until now, the best therapeutic options have not been identified. This review highlights the current perspectives of renal involvement in TA

TRPM8 channel activation reduces the spontaneous contractions in human distal colon

The transient receptor potential-melastatin 8 (TRPM8) is a non-selective Ca2+-permeable channel, activated by cold, membrane depolarization, and different cooling compounds. TRPM8 expression has been found in gut mucosal, submucosal, and muscular nerve endings. Although TRPM8 plays a role in pathological conditions, being involved in visceral pain and inflammation, the physiological functions in the digestive system remain unclear as yet. The aims of the present study were: (i) to verify the TRPM8 expression in human distal colon; (ii) to examine the effects of TRPM8 activation on colonic contractility; (iii) to characterize the mechanism of action. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting were used to analyze TRPM8 expression. The responses of human colon circular strips to different TRPM8 agonists [1-[Dialkyl-phosphinoyl]-alkane (DAPA) 2–5, 1-[Diisopropyl-phosphinoyl]-alkane (DIPA) 1–7, DIPA 1–8, DIPA 1–9, DIPA 1–10, and DIPA 1–12) were recorded using a vertical organ bath. The biomolecular analysis revealed gene and protein expression of TRPM8 in both mucosal and smooth muscle layers. All the agonists tested, except-DIPA 1–12, produced a concentration-dependent decrease in spontaneous contraction amplitude. The effect was significantly antagonized by 5-benzyloxytryptamine, a TRPM8 antagonist. The DIPA 1–8 agonist resulted in the most efficacious and potent activation among the tested molecules. The DIPA 1–8 effects were not affected by tetrodotoxin, a neural blocker, but they were significantly reduced by tetraethylammonium chloride, a non-selective blocker of K+ channels. Moreover, iberiotoxin, a blocker of the large-conductance Ca2+-dependent K+-channels, but not apamin, a blocker of small-conductance Ca2+-dependent K+ channels, significantly reduced the inhibitory DIPA 1–8 actions. The results of the present study demonstrated that TRPM8 receptors are also expressed in human distal colon in healthy conditions and that ligand-dependent TRPM8 activation is able to reduce the colonic spontaneous motility, probably by the opening of the large-conductance Ca2+-dependent K+-channels

From obesity to Alzheimer's disease through insulin resistance

Alzheimer's disease is one of the most frequent forms of dementia. It is a progressive neurodegenerative disease, characterized by presence of amyloid plaques and neurofibrillary tangles in the brain. Obesity is regarded as abnormal fat accumulation with deleterious impact on human health. There is full scientific evidence that obesity and the metabolic comorbidities (e.g., insulin resistance, hyperglycaemia, and type 2 diabetes) are related to Alzheimer's disease and likely in the causative pathway. Numerous studies have identified several overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, and inflammation. In this review, we present how obesity and the associated lipotoxicity as well as chronic inflammation initiate a state of insulin resistance that in turn, may have a role in causing the characteristic cerebral alterations of AD. In particular, we focus on the molecular mechanisms linking the obesity-induced impairment in insulin signalling to the upregulation of Aβ aggregation, tau hyper-phosphorylation, inflammation, oxidative stress and mitochondrial dysfunction