ABSTRACT
Free radical damage is implicated in the course of many diseases, including age-related dementias. Oxidative deamination of primary monoamino oxidase (MAO) produces NH3 and H2O2 with established or potential toxicity. MAO activity is increased in aged rat brain and significantly lowered by chronic hydergine (codergocrine mesylate, Sandoz) treatment. The aim of this study was to investigate the effects of hydergine on enzymatic antioxidant defense systems. Hydergine or vehicle was administered systemically to young (3 months) and aged (18 months) Sprague-Dawley rats for 20 days and 24 h after the termination of the treatment, superoxide dismutase (SOD) and catalase (CAT) activities were determined in some brain regions. SOD and CAT activities were higher in the aged animals and were further increased with hydergine treatment. The increase in SOD levels caused by hydergine treatment in the aged animals were the most prominent in the hippocampus and in the corpus striatum. There was no region-specific effect of hydergine treatment on CAT levels in aged animals. The possible causal relationship between increased MAO activity, a generator of free radicals, and increased antioxidant defense in aging brain require further investigation. Decreasing MAO levels and supporting the antioxidant enzymes may underlie the efficacy of hydergine in the treatment of age related cognitive decline.
Subject(s)
Aging/metabolism , Antioxidants/metabolism , Brain/enzymology , Ergoloid Mesylates/pharmacology , Animals , Brain/drug effects , Catalase/metabolism , Male , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolismABSTRACT
Despite the fact that hydergine has been used in the treatment of dementia for many years, its mechanism of action is still not clear. Current studies imply that the major effect of hydergine may be the modulation of synaptic neurotransmission rather than solely increasing blood flow as was once thought. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO) levels which results in decreased availability of catecholamines in the synaptic cleft. The aim of this study was to determine the effects of hydergine on the MAO activity in different brain regions (cortex, olfactory bulb, hypothalamus, hippocampus, striatum, cerebellum) of old (30 months) and adult (12 months) male Sprague-Dawley rats. In cortex and olfactory bulb MAO levels were higher in the aged group. In hippocampus and hypothalamus hydergine treatment caused significant decreases in MAO levels. An interaction between age and hydergine treatment was observed in the hypothalamus, hippocampus and cerebellum. The hydergine effect was more pronounced in the aged group in the hypothalamus and cerebellum, and more pronounced in the adult in the hippocampus. Our findings imply that increased brain MAO activity in aging can be modified by hydergine treatment in some brain regions.
Subject(s)
Aging/metabolism , Brain/enzymology , Ergoloid Mesylates/pharmacology , Monoamine Oxidase/metabolism , Nootropic Agents/pharmacology , Animals , Brain/drug effects , Hydroxyquinolines/metabolism , Kynuramine/metabolism , Male , Rats , Rats, Sprague-Dawley , Spectrometry, FluorescenceABSTRACT
1. The binding of 3H-Naloxone to opiate receptors was characterized in the frontal cortex of human post-mortem brain samples and age related changes in opiate receptors were investigated. 2. Our study revealed the presence of two binding sites with different affinities for naloxone. 3. With increasing age, the opiate receptors tend to show greater affinity for the agonistic conformation; this may imply a decline in endogenous opioid peptides with age.
Subject(s)
Cerebral Cortex/metabolism , Naloxone/metabolism , Receptors, Opioid/metabolism , Adult , Aged , Aged, 80 and over , Aging , Autopsy , Cerebral Cortex/growth & development , Cerebral Cortex/pathology , Female , Humans , Male , Middle AgedABSTRACT
1. Some disturbances in brain amino acids are reported with regard to pathological changes in schizophrenia: a reduction in GABA content and a reduced activity at some glutamatergic synapses. 2. Comparison of post-mortem brain tissue from control subjects and schizophrenic patients can provide evidence for amino acid alterations in disease. 3. The present study was undertaken to measure free amino acid concentrations in 20 brain regions obtained at autopsy, from normal persons and schizophrenics. Amino acids were extracted, esterified and separated by gas chromatography. 4. The distribution and levels of amino acids in normal persons is in accordance with similar values reported in human post-mortem brain samples by other investigators. 5. The differences in amino acids found in schizophrenic brain samples support the view of disturbed neurotransmission especially with regard to GABAergic and glutamatergic systems in schizophrenia and suggest the possible involvement of other amino acids as well.
Subject(s)
Amino Acids/analysis , Brain Chemistry , Schizophrenia/metabolism , Adult , Aged , Biomarkers/analysis , Female , Humans , Male , Middle Aged , Organ Specificity , Reference ValuesABSTRACT
The effects of prostaglandin E1(PGE1) on adrenergic mechanisms was studied, using adrenal medulla as a model tissue. Experiments were performed on male albino rats. PGE1 was introduced through the abdominal aorta. The adrenal medulla in the control and experimental animals was dissected and prepared for electronmicroscopic examinations. Catecholamine-containing vesicles in the chromaffin cells were counted and their size estimated. Statistical evaluation of the data showed that PGE1 caused an increase in the size of secretory vesicles and decrease in the total number of full vesicles, the effect being more pronounced on the adrenaline cells as compared to the noradrenaline cells.