Cerebral Isolates and Neurochemical Discovery

Abstract

I am greatly honoured by the invitation to give this Lecture, within a mile of the site of Thudichum's private laboratory and about 100 years after his last report to the Privy Council on his research on the brain (Thudichum, 1874). His investigations extended much beyond cerebral systems, which occupied some 16 years of an extremely busy scientific life. For Thudichum was a pupil of Liebig, was also a clinician, had held academic posts, and had carried out effective work on chemical constituents of urine and bile before working on the brain (see Drabkin, 1958; McIlwain, 1958a, b). After the 16 neurochemical years, he turned abruptly to other subjects. Thudichum's work on the brain sought the solution of major medical problems of his times: the deliria and coma of infectious diseases, especially of the fevers, and especially of cholera. He quite specifically sought to understand and control such deliria by chemical investigation of the brain. He was given good and for his time quite exceptional support from public funds to do this, and had assistants working with him. Thudichum found that not sufficient was known about cerebral chemistry, and set about making good the lack of knowledge. This became an end in itself, so that he concluded his preface to the book (Thudichum, 1884) in which he gives the major report on his work on the brain, with an often-quoted statement about needing to 'know the normal chemistry (of the brain) to its uttermost detail' before devising means of therapy. We may, now, smile at the 'uttermost', but we can welcome Thudichum's overwhelmingly correct view that material investigation of the brain necessarily involves chemical isolation, characterizationand measurement of its constituents. Such was the great thing Thudichum knew, and practised. I use this phrase in the following context : 'The fox knew many things, but the hedgehog knew one great thing' and rolled up accordingly, spikes exposed and impervious. For Thudichum was a prickly character and much, including probably these eponymous lectures, has followed from that characteristic. Isolates I: Chemical Constituents Thudichum's work on the brain is indeed all about isolating materials and their chemical characterization, which is why I have chosen to talk about cerebral isolates, beginning with Thudichum's type and proceeding to two others (Table 1). It is to be emphasized that Thudichum obtained his isolates in a particular way: particular both in its chemical detail, which was necessarily of his time, and also in its methodological approach, whichwas not. Heextracted, fractionatedandcrystallized to obtain substances of constant composition and properties, within the limits then available. He organized his results to give a highly schematic manner of presentation, as indicated by Table 2. Curiously, as may be noted from Table 2, Thudichum called his isolates 'principles'.

Sphingolipids and mitochondrial apoptosis

“…Sphingolipids were initially discovered in brain extract in 1870 and their nomenclature was established by J.L.W. Thudichum in 1884 (Blaschko 1975; Hawthorne 1975; McIlwain 1975). Their structure, metabolism and cellular functions have been extensively investigated and reported.…”

Podocyte Pathology and Nephropathy – Sphingolipids in Glomerular Diseases

“…Sphingolipids, more precisely sphingomyelin, cerebroside, and cerebrosulfatide were first described in 1884 by Johann L. W. Thudichum who named them for their enigmatic (“Sphinx-like”) properties (1). They are important components of the lipid rafts in plasma membranes of mammalian cells and thus contribute to the proper function of cells.…”

Effect of Low-Iodine Diet and Propylthiouracil on Glycolytic Enzymes in Brain Areas of Adult Rats

“…However, few in-depth studies have been made on the metabolic and biochemical consequences that the lack of thyroid hormones has on the CNS of adult animals. The nearly absolute dependence of tion of the brain is only complete at maturity [7,8], showing in every brain area a typical pattern of enzymatic profile which is related to the stage of development. All this suggests the study of the glycolytic response in two different experimentally induced states of hypothyroidism [low-iodine diet and propyl thiouracil (PTU)] by measuring key glyco lytic enzymes such as hexokinase (HK), phosphofructokinase (PFK), pyruvate ki nase (PK) and lactate dehydrogenase (LDH) in several brain areas.…”