Bitter tastants alter gastric-phase postprandial haemodynamics.

Ethnopharmacological Relevance: Since Greco-Roman times bitter tastants have been used in Europe to treat digestive disorders, yet no pharmacological mechanism has been identified which can account for this practice. This study investigates whether the bitter tastants, gentian root (Gentian lutea L.) and wormwood herb (Artemisia absinthium L.

Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson's disease.

Background: Data from an open label randomised controlled trial have suggested possible advantages on both motor and non-motor measures in patients with Parkinson's disease following 12 months exposure to exenatide.

Objective: Continued follow up of these same patients was performed to investigate whether these possible advantages persisted in the prolonged absence of this medication.

Methods: All participants from an open label, randomised controlled trial of exenatide as a treatment for Parkinson's disease, were invited for a further follow up assessment at the UCL Institute of Neurology.

Exenatide and the treatment of patients with Parkinson's disease.

Unlabelled: BACKGROUND. There is increasing interest in methods to more rapidly and cost-efficiently investigate drugs that are approved for clinical use in the treatment of another condition. Exenatide is a type 2 diabetes treatment that has been shown to have neuroprotective/neurorestorative properties in preclinical models of neurodegeneration.

Neuroprotection by Exendin-4 Is GLP-1 Receptor Specific but DA D3 Receptor Dependent, Causing Altered BrdU Incorporation in Subventricular Zone and Substantia Nigra.

Glucagon-like peptide-1 receptor (GLP-1R) activation by exendin-4 (EX-4) is effective in preclinical models of Parkinson's disease (PD) and appears to promote neurogenesis even in severely lesioned rats. In the present study, we determined the effects of EX-4 on cellular BrdU incorporation in the rat subventricular zone (SVZ) and substantia nigra (SN). We also determined the specificity of this effect with the GLP-1R antagonist EX-(9-39) as well as the potential role of dopamine (DA) D3 receptors.

Exendin-4 reverses biochemical and behavioral deficits in a pre-motor rodent model of Parkinson's disease with combined noradrenergic and serotonergic lesions.

Research on Parkinson's disease (PD) has mainly focused on the degeneration of the dopaminergic neurons of nigro-striatal pathway; however, post-mortem studies have demonstrated that other brain regions such as the locus coeruleus (LC) and raphe nuclei (RN) are significantly affected as well. Degeneration of these crucial neuronal cell bodies may be responsible for depressive behavior and cognitive decline present in the pre-motor stage of PD. We have thus set out to create a pre-motor rodent model of PD which mimics the early stages of the condition.

Exendin-4 reverts behavioural and neurochemical dysfunction in a pre-motor rodent model of Parkinson's disease with noradrenergic deficit.

BACKGROUND AND PURPOSE Parkinson's disease (PD) is characterized by progressive dopaminergic cell loss; however, the noradrenergic system exhibits degeneration as well. Noradrenergic deficit in PD may be responsible for certain non-motor symptoms of the pathology, including psychiatric disorders and cognitive decline. The aim of this study was to generate a pre-motor rodent model of PD with noradrenergic denervation, and to assess whether treatment with exendin-4 (EX-4), a glucagon-like peptide 1 receptor agonist, could reverse impairment exhibited by our model.

Caffeine in hot drinks elicits cephalic phase responses involving cardiac activity.

Caffeine stimulates both oropharyngeal and gut bitter taste receptors (hTAS2Rs) and so has the potential to elicit reflex autonomic responses. Coffee containing 130 mg caffeine has been reported to increase heart rate for 30 min post-ingestion. Whereas added-caffeine, in doses of 25 to 200 mg, ingested with decaffeinated coffee/tea decreases heart rate 10 to 30 min post-ingestion.

Exendin-4 treatment enhances L-DOPA evoked release of striatal dopamine and decreases dyskinetic movements in the 6-hydoxydopamine lesioned rat.

Objectives: To determine whether the glucagon-like 1 peptide analogue exendin-4 (EX-4) augments the neurochemical effects of a single L-DOPA treatment and whether EX-4 can decrease L-DOPA induced dyskinesias (LIDS).

Methods: Rats were lesioned with 6-hydroxydopamine (6-OHDA) and 7 days later given EX-4 for 7 days. The following day, rats were given L-DOPA and extracellular dopamine was measured.

The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity.

Unlabelled: The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity.

Introduction: Caffeine is detected by 5 of the 25 gustatory bitter taste receptors (hTAS2Rs) as well as by intestinal STC-1 cell lines. Thus there is a possibility that caffeine may elicit reflex autonomic responses via chemosensory stimulation.

Neuroinflammation and the prospects for anti-inflammatory treatment of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, the cause of which remains elusive. Neuroinflammation appears to be a ubiquitous pathological change in both patients and experimental models of PD, both of which present with the classical features of inflammation, but with evidence that the process has become uncontrolled. Therefore, the use of anti-inflammatory drugs in the treatment of PD appears to be a logical development.

Dopamine-dependent tuning of striatal inhibitory synaptogenesis.

Dopaminergic projections to the striatum, crucial for the correct functioning of this brain region in adulthood, are known to be established early in development, but their role is currently uncharacterized. We demonstrate here that dopamine, by activating D(1)- and/or D(2)-dopamine receptors, decreases the number of functional GABAergic synapses formed between the embryonic precursors of the medium spiny neurons, the principal output neurons of the striatum, with associated changes in spontaneous synaptic activity. Activation of these receptors reduces the size of postsynaptic GABA(A) receptor clusters and their overall cell-surface expression, without affecting the total number of clusters or the size or number of GABAergic nerve terminals.

Glucagon-like peptide 1 receptor stimulation as a means of neuroprotection.

Glucagon-like peptide 1 (GLP-1) is a relatively recently discovered molecule originating in the so-called L-cells of the intestine. The peptide has insulinotrophic properties and it is this characteristic that has predominantly been investigated. This has led to the use of the GLP-1-like peptide exendin-4 (EX-4), which has a much longer plasma half-life than GLP-1 itself, being used in the treatment of type II diabetes.

The CRF-like peptide urocortin greatly attenuates loss of extracellular striatal dopamine in rat models of Parkinson's disease by activating CRF(1) receptors.

We have recently observed that the corticotrophin releasing factor (CRF) related peptide urocortin reverses key features of nigrostriatal damage in two paradigms of Parkinson's disease. Here we have studied whether these effects are supported by a retention of striatal basal and evoked extracellular dopamine and the receptor(s) that may mediate this effect. Fourteen days following stereotaxic injections of 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS) and urocortin, extracellular dopamine levels in striata ipsilateral to injection sites of 6-OHDA/LPS and urocortin treated rats were comparable with sham injected rats, whilst rats given 6-OHDA/LPS and vehicle had considerably lower dopamine levels.

Temporal MRI assessment of intracerebral hemorrhage in rats.

Background And Purpose: MRI was used to evaluate the effects of experimental intracerebral hemorrhage (ICH) on brain tissue injury and recovery.

Methods: Primary ICH was induced in rats (n=6) by direct infusion of autologous blood into the striatum. The evolution of ICH damage was assessed by MRI estimates of T(2) and T(1sat) relaxation times, cerebral blood flow, vascular permeability, and susceptibility-weighted imaging before surgery (baseline) and at 2 hours and 1, 7, and 14 days post-ICH.

The CRF-like peptide urocortin produces a long-lasting recovery in rats made hemiparkinsonian by 6-hydroxydopamine or lipopolysaccharide.

We have recently observed that the corticotropin releasing factor related peptide urocortin (UCN) reverses key features of nigrostriatal neurodegeneration following intracerebral injection of either 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS). To determine the potential therapeutic utility of UCN here we have studied whether these effects are sustained for several weeks following peptide injection. In addition we have studied whether UCN still shows efficacy in rats with more pronounced nigrostriatal lesions.

Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease.

Background: It has recently become apparent that neuroinflammation may play a significant role in Parkinson's disease (PD). This is also the case in animal paradigms of the disease. The potential neuroprotective action of the glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4 (EX-4), which is protective against cytokine mediated apoptosis and may stimulate neurogenesis, was investigated In paradigms of PD.

Urocortin, a CRF-like peptide, restores key indicators of damage in the substantia nigra in a neuroinflammatory model of Parkinson's disease.

We have recently observed that the corticotrophin releasing hormone (CRF) related peptide urocortin (UCN) reverses key features of nigrostriatal damage in the hemiparkinsonian 6-hydroxydopamine lesioned rat. Here we have studied whether similar effects are also evident in the lipopolysaccaride (LPS) neuroinflammatory paradigm of Parkinson's disease (PD). To do this we have measured restoration of normal motor behaviour, retention of nigral dopamine (DA) and also tyrosine hydroxylase (TH) activity.

MRI estimation of contrast agent concentration in tissue using a neural network approach.

Using an MRI T(1) by multiple readout pulses (TOMROP) image set, an adaptive neural network (ANN) was trained to directly estimate the concentration of a contrast agent (CA), gadolinium-bovine serum albumin (Gd-BSA), in tissue. In nine rats implanted with a 9L cerebral tumor, MRI acquisition of TOMROP inversion-recovery data was followed by quantitative autoradiography (QAR) using radioiodinated serum albumin (RISA). QAR autoradiograms were used as a training set for the ANN.

The corticotrophin-releasing factor-like peptide urocortin reverses key deficits in two rodent models of Parkinson's disease.

The potential neuroprotective action of the corticotrophin-releasing factor-related peptide urocortin (UCN) was investigated in the rat 6-hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS) paradigms of Parkinson's disease. UCN (20 fmol) was either given at the same time as (T = 0) or 7 days after (T = +7) intracerebral 6-OHDA or LPS injection. At 14 days after 6-OHDA or LPS injection, circling behaviour was measured following apomorphine challenge.

Step-down infusions of Gd-DTPA yield greater contrast-enhanced magnetic resonance images of BBB damage in acute stroke than bolus injections.

A rat model of transient suture occlusion of one middle cerebral artery (MCA) was used to create a unilateral reperfused cerebral ischemic infarct with blood-brain barrier (BBB) opening. Opening of the BBB was visualized and quantitated by magnetic resonance (MR) contrast enhancement with a Look-Locker T(1)-weighted sequence either following an intravenous bolus injection (n=7) or during a step-down infusion (n=7) of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA). Blood levels of Gd-DTPA after either input were monitored via changes in sagittal sinus relaxation rate.

Inflammation as a causative factor in the aetiology of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting mainly the elderly, although a small proportion of PD patients develop the illness at a much younger age. In the former group, idiopathic PD patients, the causes of the illness have been the subject of longstanding debate with environmental toxins, mitochondrial dysfunction, abnormal protein handling and oxidative stress being suggested. One problem has been that the epidemiology of PD has offered few clues to provide evidence for a single major causative factor.

Angiogenesis and improved cerebral blood flow in the ischemic boundary area detected by MRI after administration of sildenafil to rats with embolic stroke.

To dynamically investigate the long-term response of an ischemic lesion in rat brain to the administration of sildenafil, male Wistar rats subjected to embolic stroke were treated with sildenafil (n=11) or saline (n=10) at a dose of 10 mg/kg administered subcutaneously 24-h after stroke and daily for an additional 6 days. Magnetic resonance images were acquired and functional performance was measured in all animals at 1 day, 2 days and weekly for 6 weeks post-stroke. All rats were sacrificed 6 weeks after stroke and endothelial barrier antigen immunostaining was employed for morphological analysis and quantification of cerebral vessels.

Effects of amantadine and budipine on antidepressant drug-evoked changes in extracellular dopamine in the frontal cortex of freely moving rats.

NMDA receptors play a role in the aetiology of depression with non-competitive NMDA receptor antagonists such as amantadine showing synergy with conventional antidepressants. To advance a neurochemical rational for these findings, we have studied the effects of administration of amantadine and budipine with the antidepressants reboxetine (REB), paroxetine (PAROX) and clomipramine (CLOM) on extracellular DA in rats using microdialysis. Acutely, amantadine (40 mg/kg) or budipine (10 mg/kg) did not significantly alter extracellular DA.

Chronic treatment with antidepressant drugs reversibly alters NMDA mediated regulation of extracellular 5-HT in rat frontal cortex.

Treatment of depression is largely based upon the monoamine theory of the illness. However, current therapies are only efficacious in 70-80% of patients indicating that other factors are involved. One mechanism could involve glutamatergic NMDA receptors since NMDA receptor antagonists have antidepressant like properties in paradigms of the illness.

Characterization of cerebral tissue by MRI map ISODATA in embolic stroke in rat.

ISODATA using MRI parameter-weighted images has been previously employed to characterize ischemic cell damage after stroke in rats. In an effort to increase the objectivity and to further automate the ISODATA, MRI parameter maps were now employed. Male Wistar rats were subjected to embolic stroke and received treatment via a femoral vein at 4 h post-stroke.