The effects of antidepressants on the retention and metabolism of [3H]-norepinephrine in rat brain slices

Tricylic antidepressants acutely decrease the neuronal retention of [3H]-norepinehrine ([3H]-NE) by blocking neuronal membrane uptake and/or vesicular uptake and binding. To distinguish between effects upon the plasma membrane and upon the vesicular membrane, the retention, deamination, and O-methylation of [3H]-NE by rat brain slices were investigated in the presence of several antidepressant agents. The effects of antidepressants were compared to those of the prototype inhibitors, cocaine and reserpine, using slices of hypothalamus, brainstem. parietal cortex and caudate nucleus. Cocaine, which inhibits neuronal membrane uptake, decreased both the deamination and retention of [3H]-NE, while O-methylation was increased. Reserpine, which inhibits vesicular transport and binding, increased deamination, while it reduced retention without affecting the 0-methylation of [3H]-NE. The effects of desipramine, a prototype tricyclic antidepressant, were found to depend on the concentration. At low concentrations (10-9-10-8M), desipramine inhibited the retention and deamination of [3H]-NE in each brain region except the caudate. At higher concentrations (10-7-10w-4M), the retention of [3H]-NE was reduced further. However, deamination was increased in the caudate and, in the other three regions, deamination did not decrease further. Nortriptyline and protriptyline had actions similar to desipramine, whereas, iprindole did not affect [3H]-NE retention. These results suggest that tricyclic antidepressants are not specific selective inhibitors of neuronal membrane transport.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24412/1/0000682.pd

The waking brain: an update

Wakefulness and consciousness depend on perturbation of the cortical soliloquy. Ascending activation of the cerebral cortex is characteristic for both waking and paradoxical (REM) sleep. These evolutionary conserved activating systems build a network in the brainstem, midbrain, and diencephalon that contains the neurotransmitters and neuromodulators glutamate, histamine, acetylcholine, the catecholamines, serotonin, and some neuropeptides orchestrating the different behavioral states. Inhibition of these waking systems by GABAergic neurons allows sleep. Over the past decades, a prominent role became evident for the histaminergic and the orexinergic neurons as a hypothalamic waking center

The Biochemical and Cellular Basis for Nutraceutical Strategies to Attenuate Neurodegeneration in Parkinson’s Disease

Future therapeutic intervention that could effectively decelerate the rate of degeneration within the substantia nigra pars compacta (SNc) could add years of mobility and reduce morbidity associated with Parkinson’s disease (PD). Neurodegenerative decline associated with PD is distinguished by extensive damage to SNc dopaminergic (DAergic) neurons and decay of the striatal tract. While genetic mutations or environmental toxins can precipitate pathology, progressive degenerative succession involves a gradual decline in DA neurotransmission/synaptic uptake, impaired oxidative glucose consumption, a rise in striatal lactate and chronic inflammation. Nutraceuticals play a fundamental role in energy metabolism and signaling transduction pathways that control neurotransmission and inflammation. However, the use of nutritional supplements to slow the progression of PD has met with considerable challenge and has thus far proven unsuccessful. This review re-examines precipitating factors and insults involved in PD and how nutraceuticals can affect each of these biological targets. Discussed are disease dynamics (Sections 1 and 2) and natural substances, vitamins and minerals that could impact disease processes (Section 3). Topics include nutritional influences on α-synuclein aggregation, ubiquitin proteasome function, mTOR signaling/lysosomal-autophagy, energy failure, faulty catecholamine trafficking, DA oxidation, synthesis of toxic DA-quinones, o-semiquinones, benzothiazolines, hyperhomocyseinemia, methylation, inflammation and irreversible oxidation of neuromelanin. In summary, it is clear that future research will be required to consider the multi-faceted nature of this disease and re-examine how and why the use of nutritional multi-vitamin-mineral and plant-based combinations could be used to slow the progression of PD, if possible

A simple, rapid method for circular paper chromatography

I HAVE recently developed in our laboratory the following method for the circular development of a large paper disk which has the advantages of (a) rapidity, requiring no more than two and a half hours for a satisfactory separation of sugars and amino-acids, and (b) simplicity, as it does not need the various devices of other workers1,2. © 1958 Nature Publishing Group

Quantitative Determination of Reducing Sugars after Separation by Paper Chromatography

► A method is described for the quantitative determination of reducing sugars after chromatographic separation. The experimental error of the method amounts to 0.8 to 5.4%, depending upon the quantity of the sugar. © 1959, American Chemical Society. All rights reserved