Abstract Transient occlusion of common carotid arteries in gerbils is a simple and widely used model for assessing histological and functional consequences of transient forebrain ischemia and ...neuroprotective action of pharmaceuticals. In the present study we aimed to introduce additional behavioural tests as novel object recognition and food-motivated hole-board learning in order to measure attention and learning capacity in gerbils. For validating these cognitive tests the effects of ageing (4, 9 and 18 months) and those of transient forebrain ischemia induced by bilateral carotid occlusion at 9 months of age were investigated. Neuronal cell death was estimated in the hippocampus using TUNEL and caspase-3 double fluorescence labelling and confocal microscopy. Ageing within the selected range although influenced ambulatory activity, did not considerably change attention and memory functions of gerbils. As a result of transient ischemia a selective neuronal damage in CA1 and CA2 regions of the hippocampus has been observed and tested 4 days after the insult. Ischemic gerbils became hyperactive, but showed decreased attention and impaired spatial memory functions as compared to sham-operated controls. According to our results the novel object recognition paradigm and the hole-board spatial learning test could reliably be added to the battery of conventional behavioural tests applied previously in this species. The novel tests can be performed within a wide interval of adult age and provide useful additional methods for assessing ischemia-induced cognitive impairment in gerbils.
Enhancer regulation is a new control mechanism in the brain Knoll, J., 2003. Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired ...drives. Neurochemical Research 28(8), 1275–1297. Enhancer substances exert their effect in bi-modal form with a highly characteristic dose-dependency. Two bell-shaped concentration curves have been published. The one in ultra low concentration range (fM) specific form of enhancer regulation and the other at high concentration (100 μM) non-specific form of enhancer regulation. Catecholaminergic neurons proved to be enhancer-sensitive cells. Since rat PC12 cells and human brain endothelial cells (HBEC) work under catecholaminergic influence, it was reasonable to expect that both the specific and non-specific form of the enhancer regulation might be detectable in these cells. We tested this possibility on these cultured cells under normoxia and hypoxia–reoxygenation. After 1 h hypoxia produced by Argon gas and 0, 2, 4, and 20 h reoxygenation the cell loss was calculated by propidiumiodide assay and the cell activity was investigated by Alamar Blue assay colorimetric measurement. The percentages of living and necrotic cells were expressed after propidiumiodide staining. Broad scale concentrations of the two compounds (1 fM–100 μM) were added to the culture strait after the oxygen deprivation. (−)-BPAP and (−)-deprenyl, due to their enhancer effect, exerted a significant cytoprotective effect on both HBECs and PC12 cells. In harmony with Knoll's publications we were able to demonstrate by the aid of (−)-BPAP and (−)-deprenyl that both HBEC and PC12 are enhancer-sensitive cells. We detected the specific form of the enhancer regulation in the ultra low concentration range (fM–pM) and also the non-specific form of the enhancer regulation was visible (mM–μM).
Beneficial effects of dehydroepiandrosterone (DHEA) pretreatment were reported in ischaemia/reperfusion (I/R)-induced kidney damage.
To investigate the mechanism of DHEA pretreatment during renal I/R ...injury, the left renal pedicles of DHEA- G(DHEA); 4.0 mg/kg/day DHEA dissolved in propylene glycol (PG) and PG-pretreated male Wistar rats (G(PG)) were clamped for 55 min followed by 2 (T(2)) and 24 h (T(24)) of reperfusion. Sham-operated, non-clamped animals (T(0)) served as controls in both groups. Renal function, kidney morphology and interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) expression were determined in the kidneys of both groups.
Renal functional parameters and kidney structure did not differ in G(DHEA) versus G(PG) at any time point. Renal mRNA expression of IL-1beta was lower at T(0), while IL-6 at T(2) was lower in G(DHEA) than in G(PG).While renal VEGF mRNA expression remained unchanged, protein levels were increased at T(2) and T(24 )compared to T(0) kidneys in both groups. VEGF protein levels were lower at T(2) and T(24 )in G(DHEA) than in G(PG).
We found that DHEA pretreatment alters renal IL-1beta, IL-6 and VEGF synthesis. Moreover, contrary changes in VEGF mRNA and protein levels suggest that VEGF synthesis - distinct from other organs - might be primarily posttranscriptionally regulated in postischaemic rat kidneys.
Abstract
Prevalence estimations for mitochondrial disorders still vary widely and only few epidemiologic studies have been carried out so far. With the present work we aim to give a comprehensive ...overview about frequencies of the most common mitochondrial mutations in Hungarian patients. A total of 1328 patients were tested between 1999 and 2012. Among them, 882 were screened for the m.3243A > G, m.8344A > G, m.8993T > C/G mutations and deletions, 446 for LHON primary mutations. The mutation frequency in our cohort was 2.61% for the m.3243A > G, 1.47% for the m.8344A > G, 17.94% for Leber's Hereditary Optic Neuropathy (m.3460G > A, m.11778G > A, m.14484T > C) and 0.45% for the m.8993T > C/G substitutions. Single mtDNA deletions were detected in 14.97%, while multiple deletions in 6.01% of the cases. The mutation frequency in Hungarian patients suggestive of mitochondrial disease was similar to other Caucasian populations. Further retrospective studies of different populations are needed in order to accurately assess the importance of mitochondrial diseases and manage these patients.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
INTRODUCTIONWernicke encephalopathy (WE) and Wernicke-Korsakoff syndrome (WKS) are well-known disorders caused by thiamine deficiency. In addition to the classical concept of these diseases, some ...literature data suggest a connection between mitochondrial dysfunction and WE/WKS. Psychotic disorders and WKS seem to run in families, as the deficiency of the oxidative phosphorylation can be a trigger factor in psychotic events and WE/WKS as well. We present a patient harbouring the m.A3243G mtDNA mutation with the clinical and magnetic resonance imaging (MRI) findings of WKS who developed schizophrenia with predominantly negative symptoms some years later. CASE PRESENTATIONA 27-year-old woman was referred to our clinic with severe weight loss after severe vomiting episodes, memory dysfunction and gait ataxia. Family history, as well as clinical, imaging and laboratory findings suggested a mitochondrial aetiology of her symptoms. Brain MRI detected bilateral mild thalamic lesions and loss of corpus mammillae, indicating Wernicke encephalopathy. Genetic testing detected an m.A3243G mtDNA mutation, which has been frequently associated with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes. High-dose vitamin B1 supplementation with supportive antioxidant therapy improved the patient's memory and learning disturbance; however, some months later she developed psychosis with predominantly negative symptoms and her cognitive functions deteriorated again. Both cognitive and negative symptoms responded well to cariprazine monotherapy. DISCUSSIONMitochondrial disease due to mtDNA alteration can be a rare cause of WE. In addition to vitamin B1 supplementation, cariprazine with significant dopamine D3 receptor binding can be useful to treat the predominantly negative symptoms and cognitive dysfunction in patients with mitochondrial dysfunction. CONCLUSIONWe assume that patients with a mitochondrial disorder might be prone to develop WE/WKS and therefore need tailored supportive therapy during metabolic crisis as well as symptom-based personalized antipsychotic treatment.
PDF
