T. L. Perry

REGIONAL DISTRIBUTION OF AMINO ACIDS IN HUMAN BRAIN OBTAINED AT AUTOPSY

Abstract— Contents (μmol/g wet wt.) of 35 free amino acids and related compounds were measured in 12 different regions of each of five human brains. Specimens were obtained at autopsy from patients who died suddenly without previous brain disease. These data may serve for later comparison with contents of amino compounds in similar regions of the brains of patients dying with various neurological or psychiatric disorders.

CSF amino acids and plasma--CSF amino acid ratios in adults.

SEVERAL groups of investigators have reported mean concentrations of free amino acids in the CSF of adult subjects, using automated ion exchange chromatographic techniques (PERRY & JONES, 1961; DICKINSON & HAMILTON, 1966; PERRY et al., 1969; VAN SANDE et al., 1970; GJESSING et al., 1972). In all of these studies except one (GJESSING et al., 1972), the number of subjects examined was either small, or values were not reported for some of the measurable amino compounds. We present here mean values for all 28 readily measurable amino compounds found in the CSF of 43 adult subjects. Data are also given for the mean concentrations of amino acids in fasting plasma from 77 healthy adults, and we call attention to some anomalies in the plasma-CSF ratios of certain amino compounds.

FREE AMINO ACIDS AND RELATED COMPOUNDS IN BIOPSIES OF HUMAN BRAIN

Abstract— Contents (μmol/g wet wt.) of 35 free amino acids and related compounds were measured in biopsies of human brain from ten patients. Brain specimens were frozen in liquid nitrogen within 10 sec of their removal at neurosurgery; thus, the values found should approximate those which occur in living brain.

γ-AMINOBUTYRIC-ACID DEFICIENCY IN BRAIN OF SCHIZOPHRENIC PATIENTS

Gamma-aminobutyric acid (G.A.B.A.) was measured in the nucleus accumbens and thalamus of brains from patients who had died with schizophrenia or Huntingtons chorea (H.C.) and from control subjects. Mean G.A.B.A. content was significantly reduced in both brain areas in schizophrenia and in H.C. Extraneous factors, such as age, interval from death to necropsy, cause of death, and drug use, did not readily explain the observed reduction in brain G.A.B.A. G.A.B.A. deficiency may be a biochemical characteristic of some forms of schizophrenia.

SUSTAINED DRUG-INDUCED ELEVATION OF BRAIN GABA IN THE RAT

Abstract— The contents of GABA, homocarnosine, and β‐alanine can be raised in rat brain for long periods of time by the continued administration of phenelzine, aminooxyacetic acid (AOAA), or isonicotinic acid hydrazide (INH). These 3 compounds apparently act by preferential inhibition of the enzyme GABA aminotransferase (GABA‐T). Oral administration of phenelzine (20 mg/kg per day) caused a 25–50 per cent increase in GABA levels in rat brain, but produced appreciable toxic side effects. A similar increase in GABA levels in brain resulted from oral administration to rats of INH in a dosage of 60 mg/kg per day, without production of any obvious toxic effects. Simultaneous administration of large doses of pyridoxine did not abolish the GABA‐elevating effect of INH. Brain GABA levels in the rat were increased by approx. 50 per cent by daily injections of AOAA (2.5 mg/kg per day). At this low dosage, AOAA injections in rats could be continued for at least 6 weeks without producing evident toxic effects. Oral administration of large amounts of GABA, on the other hand, failed to increase the content of GABA in the brains of rats not treated with GABA‐T inhibitors, and failed to produce any further increase of brain GABA levels in rats treated with AOAA.

GABA content and glutamic acid decarboxylase activity in brain of Huntington's chorea patients and control subjects.

—GABA contents are significantly decreased in the caudate nucleus, putamen‐globus pallidus, substantia nigra, and occipital cortex in autopsied brain from Huntingtons chorea patients, as compared to values in the same regions from control subjects who have died without neurological disease. Homocarnosine levels are lower in choreic than in control brain, but only in the putamen‐globus pallidus and the cerebellar cortex are the differences significant.

AMINES OF HUMAN WHOLE BRAIN

IN A PREVIOUS paper (PERRY, HANSEN, FOULKS and LING, 1965) we described a number of aliphatic and aromatic amines detected in whole brain of normal cats by means of a technique which combines ion exchange column chromatography and paper chromatography. This technique has an advantage over the more commonly employed spectrophotofluorimetric and biological assays of brain amines, in that each compound is separated from other bases. is visualized, and can be identihed with a considerable demee 01 certaintv. We now wish to report the results of application ofthis technique to a suryey of amnes present in human brain. The present study was carried out on whole brain obtained from persons dying without known neurological or mental disease,and was designed to provide information as to the variety of amines present in normal human brain and to determine the effect on brain amine content of slow death and delay in autopsy. Twelve amines were positively identified in human brain. One of them, monoacetylputrescine, has not previously been reported in mammalian tissues or physiological fluids. The amount of 5-HT and histamine found in whole human brain was considerably less than has been reported in brain tissue of lower mammals.

PLASMA-AMINOACID LEVELS IN HUNTINGTON'S CHOREA

Abstract Concentrations of six aminoacids were found to be significantly lower in fasting plasma of a group of nineteen patients with Huntingtons chorea, than in the plasma of a group of twenty adult controls or a group of eighteen inpatients with chronic schizophrenia. These aminoacids were proline, alanine, valine, isoleucine, leucine, and tyrosine. Similar, but less striking, changes were found in the cerebrospinal fluid of Huntingtons chorea patients as compared with the cerebrospinal fluid of controls. The decrease in plasma concentrations of certain aminoacids in Huntingtons chorea does not seem to be caused by environmental factors, and may be a secondary reflection of the basic biochemical error underlying this hereditary disorder.

HOMOCARNOSINE IN HUMAN CEREBROSPINAL FLUID: AN AGE-DEPENDENT PHENOMENON

—Homocarnosine, rather than carnosine, is the major imidazole dipeptide present in human CSF. This compound can be readily detected in the CSF of normal infants and young children, while it is either not detectable or is present only in very small concentrations in the CSF of normal adult subjects. Slightly greater amounts of homocarnosine can be found in the CSF of some adults with neurological disorders.

SERUM-CARNOSINASE DEFICIENCY IN CARNOSINÆMIA

Abstract Normal human serum contains an enzyme that hydrolyses the dipeptides carnosine and anserine into their constituent aminoacids. An assay method was developed which showed that serum-carnosinase activity is relatively high in normal adults, and lower in young children. Little or no carnosinase activity was found in the sera of two children who had carnosinaemia associated with neurological disease and mental defect. Serum-carnosinase determination may prove useful in other patients who are found to have a non-dietary carnosinaemia or carnosinuria.