scholarly journals A New Method to Measure Brain Serotonin Synthesis in vivo. II. A Practical Autoradiographic Method Tested in Normal and Lithium-Treated Rats

1990 ◽  
Vol 10 (1) ◽  
pp. 13-21 ◽  
Author(s):  
S. Nagahiro ◽  
A. Takada ◽  
M. Diksic ◽  
T. L. Sourkes ◽  
K. Missala ◽  
...  

We describe here a practical autoradiographic method to estimate the rate of serotonin synthesis in brain. A two-time point method (60 and 150 min after injection of a-[14C]methyl-l-tryptophan) was first evaluated in 14 normal rats (7 at each time point). After this the method was tested in lithium-treated rats. In normal rats the rate of serotonin synthesis measured by the two-time point method generally correlated with known concentrations of tryptophan hydroxylase. The rate of synthesis in lithium-treated rats was compared with that in shamtreated rats (NaCl treatment). The results showed a significant increase in the synthesis rate in some cerebral structures. The greatest increases in the serotonin synthesis rate, attributable to the lithium treatment, were observed in the parietal cortex (52%) and caudate nucleus (47%). This is the first investigation to demonstrate, with autoradiographic resolution (∼100 μm), the differential changes in the rate of serotonin synthesis in the brain. Lithium had no significant effect on the rate of synthesis in the pineal gland.

2016 ◽  
Vol 30 (10) ◽  
pp. 1028-1035 ◽  
Author(s):  
Tomas Furmark ◽  
Ina Marteinsdottir ◽  
Andreas Frick ◽  
Kerstin Heurling ◽  
Maria Tillfors ◽  
...  

1990 ◽  
Vol 10 (1) ◽  
pp. 1-12 ◽  
Author(s):  
M. Diksic ◽  
S. Nagahiro ◽  
T. L. Sourkes ◽  
Y. L. Yamamoto

We describe here an autoradiographic method to measure the in vivo rate of serotonin synthesis in rat brain. The method is based on the use of the l-tryptophan analogue a-methyl-l-tryptophan ( a-MTrp), which is converted in vivo into a-methylserotonin ( a-M5HT). Since a-M5HT is not a substrate for monoamine oxidase, it is accumulated in the brain tissue. Data are presented to confirm time-dependent conversion of a-MTrp into a-M5HT in the dorsal raphe nucleus and also in the pineal body, an organ outside the blood–brain barrier. It has also been shown that washing brain slices in 10% trichloroacetic acid results in <3% incorporation of a-MTrp into brain proteins. The rates of synthesis are calculated in several grossly dissected brain structures by using tracer kinetics and a three-compartment biological model. The half-life of the precursor pool is estimated to be ∼20 min. The rate of serotonin synthesis is highest in the pineal body.


1997 ◽  
Vol 17 (6) ◽  
pp. 659-669 ◽  
Author(s):  
Otto Muzik ◽  
Diane C. Chugani ◽  
Pulak Chakraborty ◽  
Thomas Mangner ◽  
Harry T. Chugani

We describe the tracer kinetic analysis of [C-11]-labeled alpha-methyl-tryptophan (AMT), an analogue of tryptophan, which has been developed as a tracer for serotonin synthesis using positron emission tomography (PET) in human brain. Dynamic PET data were acquired from young healthy volunteers (n = 10) as a series of 22 scans covering a total of 60 minutes and analyzed by means of a three-compartment, four-parameter model. In addition, functional images of the K-complex were created using the Patlak-plot approach. The application of a three-compartment model resulted in low identifiability of individual k-values, especially that of k3. Model identifiability analysis using a singular value decomposition of the final sensitivity matrix showed parameter identifiability to increase by 50% when the Patlak-plot approach was used. K-complex values derived by the Patlak-plot approach overestimated the compartmental values by 10 to 20%, because of the violation of the dynamic equilibrium assumption. However, this bias was fairly constant in all structures of the brain. The rank order of K-complex values from different brain regions corresponded well to the regional concentrations of serotonin in human brain (P < 0.0001). These results indicate that the Patlak-plot method can be readily applied to [C-11]AMT data in order to create functional images of the K-complex, reflecting serotonin synthesis rate, within an acceptable error margin.


2004 ◽  
Vol 31 (8) ◽  
pp. 1013-1019
Author(s):  
Hidehiko Okazawa ◽  
Sadahiko Nishizawa ◽  
Tatsuro Tsuchida ◽  
Yoshiharu Yonekura ◽  
Mirko Diksic

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