Asymmetric intra and inter-hemispheric subcellular rat brain correlation of arginyl-aminopeptidase activity during development and aging.

The functional significance of brain asymmetry is still largely unknown. Studying the level of correlation of neuropeptide-degrading activities between subcellular fractions such as synaptosomal, of the left and right hemispheres of male rats during development and aging could provide relevant data on their functional role during these periods. The present study analyzes the level of correlation of a enkephalin- or angiotensin III-degrading activity, such as membrane-bound arginyl-aminopeptidase activity (M-B ArgAP) between the left versus right homogenate and/or synaptosomal subcellular fractions obtained and processed independently from both brain hemispheres during development and aging.

Correlational Study of Aminopeptidase Activities between Left or Right Frontal Cortex versus the Hypothalamus, Pituitary, Adrenal Axis of Spontaneously Hypertensive Rats Treated with Hypotensive or Hypertensive Agents.

It has been suggested that the neuro-visceral integration works asymmetrically and that this asymmetry is dynamic and modifiable by physio-pathological influences. Aminopeptidases of the renin-angiotensin system (angiotensinases) have been shown to be modifiable under such conditions. This article analyzes the interactions of these angiotensinases between the left or right frontal cortex (FC) and the same enzymes in the hypothalamus (HT), pituitary (PT), adrenal (AD) axis (HPA) in control spontaneously hypertensive rats (SHR), in SHR treated with a hypotensive agent in the form of captopril (an angiotensin-converting enzyme inhibitor), and in SHR treated with a hypertensive agent in the form of the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME).

Aminopeptidase Activities Interact Asymmetrically between Brain, Plasma and Systolic Blood Pressure in Hypertensive Rats Unilaterally Depleted of Dopamine.

Brain dopamine, in relation to the limbic system, is involved in cognition and emotion. These functions are asymmetrically processed. Hypertension not only alters such functions but also their asymmetric brain pattern as well as their bilateral pattern of neurovisceral integration.

Seventy-Two-Hour LRRK2 Kinase Activity Inhibition Increases Lysosomal GBA Expression in H4, a Human Neuroglioma Cell Line.

Mutations in LRRK2 and GBA1 are key contributors to genetic risk of developing Parkinson's disease (PD). To investigate how LRRK2 kinase activity interacts with GBA and contributes to lysosomal dysfunctions associated with the pathology of PD. The activity of the lysosomal enzyme β-Glucocerebrosidase (GCase) was assessed in a human neuroglioma cell model treated with two selective inhibitors of LRKK2 kinase activity (LRRK2-in-1 and MLi-2) and a GCase irreversible inhibitor, condutirol-beta-epoxide (CBE), under 24 and 72 h experimental conditions.

Asymmetric Interaction of Neuropeptidase Activities between Cortico-Limbic Structures, Plasma and Cardiovascular Function after Unilateral Dopamine Depletions of the Nigrostriatal System.

In emotional processing, dopamine (DA) plays an essential role, and its deterioration involves important consequences. Under physiological conditions, dopamine exhibits brain asymmetry and coexists with various neuropeptides that can coordinate the processing of brain functions. Brain asymmetry can extend into a broader concept of asymmetric neurovisceral integration, including behavior.

Asymmetrical response of aminopeptidase A in the medial prefrontal cortex and striatum of 6-OHDA-unilaterally-lesioned Wistar Kyoto and spontaneously hypertensive rats.

Aminopeptidase A is responsible for the hydrolysis of angiotensin II and cholecystokinin. By measuring its activity we obtain a reflection of the functional status of its endogenous substrates. Dopamine coexists with these neuropeptides in striatum and prefrontal cortex.

Structural genomic variations and Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease, whose prevalence is projected to be between 8.7 and 9.3 million by 2030.

Bilateral distribution of enkephalinase activity in the medial prefrontal cortex differs between WKY and SHR rats unilaterally lesioned with 6-hydroxydopamine.

Changes in the basal brain bilateral morphologic, neurochemical and/or functional patterns may be partly responsible for some brain disorders such as those involving mood. WKY and SHR strains as well as 6-hydroxydopamine (6-OHDA)-lesioned animals are validated models for the study of mood disorders. Because dopamine and enkephalins are involved in anxiety-related behaviors, the aim of our study was to analyze enkephalinase activity, assayed as aminopeptidase M activity, in the left and right medial prefrontal cortex (mPFC) of WKY and SHR treated with saline (sham group) or following left or right intrastriatal injections of the neurotoxic 6-OHDA.

Analysis of the genetic variability in Parkinson's disease from Southern Spain.

To date, a large spectrum of genetic variants has been related to familial and sporadic Parkinson's disease (PD) in diverse populations worldwide. However, very little is known about the genetic landscape of PD in Southern Spain, despite its particular genetic landscape coming from multiple historical migrations. We included 134 PD patients in this study, of which 97 individuals were diagnosed with late-onset sporadic PD (LOPD), 28 with early-onset sporadic PD (EOPD), and 9 with familial PD (FPD).

Tissue distribution of CysAP activity and its relationship to blood pressure and water balance.

Aims: To better understand the functional role of soluble (Sol) and membrane-bound (MB) cystinyl-aminopeptidase (CysAP) activities, we studied differentially their organ distribution in adult male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR)with or without treatment with captopril.We searched for a possible tissue-specific association of CysAP with water balance and blood pressure.

Main Methods: We used twenty WKY rats distributed in ten controls and ten captopril-treated, and sixteen SHR divided in eight controls and eight captopril-treated.

Interaction of neuropeptidase activities in cortico-limbic regions after acute restraint stress.

Brain enkephalin, vasopressin and oxytocin are anxiolytic agents involved in the stress response. Acute restraint stress influences certain neuropeptidase activities, such as some enkephalin-degrading peptidases and vasopressinase/oxytocinase, in the medial prefrontal cortex (mPFC), amygdala (AM) or hippocampus (HC), which are involved in this response. Because these regions form a unified circuit and cooperate in their response to stress, it is important to analyze the profile of the regional distribution of these activities as well as their inter-regional model of interaction in this circuit.

An examination of the mechanisms involved in secondary clinical failure to adalimumab or etanercept in inflammatory arthropathies.

Background: Biological therapies against tumor necrosis factor α have revolutionized the treatment of several inflammatory rheumatic diseases. However, 30% of responders will present a clinical failure after having controlled the disease for at least 6 months (secondary clinical failure). Biological therapies may induce an unwanted immune response, which may alter the bioavailability of the drug causing a loss of clinical response.

Brain, heart and kidney correlate for the control of blood pressure and water balance: role of angiotensinases.

The renin-angiotensin system (RAS) plays a major role in the control of blood pressure (BP) and water balance by coordinating brain, heart and kidney functions, connected with each other by hormonal and neural mechanisms through the autonomic nervous system (ANS). RAS function may be monitored by the study of the enzymes (angiotensinases) involved in the metabolism of its active peptides. In order to study the relationship between the brain-heart-kidney axis and the control of BP and water balance, we analyzed the correlation of angiotensinase activities, assayed as arylamidase activities, between hypothalamus, left ventricle, renal cortex and renal medulla, collected from Wistar-Kyoto and spontaneously hypertensive rats, treated or not treated with L-NAME [N(G)-nitro-L-arginine methyl ester].

[Proteomic biomarkers in Parkinson's disease].

Parkinson's disease (PD) is a neurodegenerative disorder that affects movement and is caused by the death of the dopaminergic neurons in the compact part of the substantia nigra. Its diagnosis is essentially clinical, but although the signs and symptoms of PD are well known, the rate of diagnostic error is relatively high. It is estimated that 10-30% of patients initially diagnosed with PD are later reclassified.

The brain-heart connection: frontal cortex and left ventricle angiotensinase activities in control and captopril-treated hypertensive rats-a bilateral study.

The model of neurovisceral integration suggests that the frontal cortex (FC) and the cardiovascular function are reciprocally and asymmetrically connected. We analyzed several angiotensinase activities in the heart left ventricle (VT) of control and captopril-treated SHR, and we search for a relationship between these activities and those determined in the left and right FC. Captopril was administered in drinking water for 4 weeks.

Asymmetrical effect of captopril on the angiotensinase activity in frontal cortex and plasma of the spontaneously hypertensive rats: expanding the model of neuroendocrine integration.

There is a reciprocal connection between the frontal cortex (FC) and cardiovascular function, and this connection is functionally lateralized. The possible pathophysiological impact of neuroendocrine asymmetries is largely underestimated. Our aim was to examine the activity of soluble (SOL) and membrane-bound (MB) aminopeptidases (APs) involved in the renin-angiotensin system in the peripheral plasma and in the left and right FC, in both untreated (control) and captopril-treated spontaneously hypertensive rats (SHRs).

Oxidative stress and aminopeptidases in Parkinson's disease patients with and without treatment.

Background/objective: Mitochondrial dysfunction, oxidative stress and protein metabolism impairment are the main molecular events underlying the pathogenesis of Parkinson's disease (PD). However, only few studies have addressed the changes produced by these phenomena in the blood of PD patients. Our purpose was to compare oxidative stress between newly diagnosed PD patients (ntPD) and PD patients under treatment (tPD).

Lateralized response of oxytocinase activity in the medial prefrontal cortex of a unilateral rat model of Parkinson's disease.

Individuals in the early stage of Parkinson's disease exhibit cognitive impairments as a result of hemisphere damage. The mesocortical dopamine system, particularly the medial prefrontal cortex (mPFC), is implicated in cognitive functions and is characterized by an asymmetric organization. Oxytocinase activity (OX) is also asymmetrically distributed in the mPFC of normal rats and is involved in cognitive functions.

Oxidative stress and plasma aminopeptidase activity in Huntington's disease.

Huntington's disease (HD) is a genetic neurodegenerative disorder. Oxidative stress, mitochondrial dysfunction, and protein metabolism impairment have been implicated in its pathogenesis. However, the contribution of these phenomena to HD onset or progression is not well known, and they have been less studied in peripheral blood.

Plasma alpha-synuclein in patients with Parkinson's disease with and without treatment.

Alpha-synuclein (alpha-syn) is an intracellular protein with a high tendency to aggregation. It is the major component of Lewy bodies and may play a key role in the pathogenesis of Parkinson's disease (PD). alpha-Syn is also released by neurons and can be detected in biological fluids, such as plasma.

Stress influences brain enkephalinase, oxytocinase and angiotensinase activities: a new hypothesis.

Brain enkephalin and oxytocin are anxiolytic agents involved in the response mechanism to stress. Degrading enzymes such as enkephalinase and oxytocinase could also be associated with this response. The effect of acute immobilization stress on enkephalinase and oxytocinase activities was determined in the soluble and membrane fractions of the medial prefrontal cortex, hippocampus and amygdala using alanyl- and leucyl-beta-naphthylamide as substrates, the latter in the presence and absence of 20 mM L-methionine.

Asymmetrical response of aminopeptidase A and nitric oxide in plasma of normotensive and hypertensive rats with experimental hemiparkinsonism.

Aminopeptidases and dopamine (DA) exhibit asymmetries in the brain that are reflected in the peripheral response to unilateral striatal DA depletions (experimental hemiparkinsonism). This might be due to asymmetries in the autonomic innervation of the peripheral vessels. Nitric oxide (NO) is released through vascular sympathetic activation.