i i \Main" | 2003/4/21 | 18:25 | page 1 | #1 i i JOURNAL AND PROCEEDINGS OF THE R O Y A L S O C I E T Y O F N E W S O U T H W A L E S Volume 135 Parts 3 and 4 (Nos 405{406) 2003 ISSN 0035-9173 PUBLISHED BY THE SOCIETY PO BOX 1525, MACQUARIE CENTRE, NSW 2113 Issued April 2003 i i i i i i \Main" | 2003/4/21 | 18:25 | page 56 | #2 i i THE ROYAL SOCIETY OF NEW SOUTH WALES OFFICE BEARERS FOR 2002-2003 Patrons His Excellency the Right Reverend Dr Peter Hollingworth AC, OBE, Governor General of the Commonwealth of Australia. Her Excellency Professor Marie Bashir, AC, Governor of New South Wales. President Mr D.A. Craddock, BSc(Eng) NSW, Grad.Cert. Management UWS. Vice Presidents Prof. P.A. Williams, BA (Hons), PhD Macq. Dr W.E. Smith, MSc Syd, MSc Oxon, PhD NSW, MInstP, MAIP. Mr C.F. Wilmot Hon. Secretary (Gen.) vacant (acting Hon. Sec. Prof. P.A. Williams) Hon. Secretary (Ed.) Mrs M. Krysko von Tryst, BSc, Grad.Dip.Min.Tech NSW, MAusIMM. Hon. Treasurer Prof R.A. Creelman, BA, MSc, PhD Hon. Librarian Dr E.V. Lassak, MSc, PhD NSW, ASTC, FRACI Councillors Mr J.R. Hardie, BSc Syd, FGS, MACE. Prof. J. Kelly, BSc Syd, PhD Reading, DSc NSW Ms K. F. Kelly, BSc(Hons) Mr M.F. Wilmot, BSc Prof M.A. Wilson, PhD, DSc. Auck, FRACI, C.Chem. Southern Highlands Rep. Mr C.M. Wilmot The Society originated in the year 1821 as the Philosophical Society of Australasia. Its main function is the promotion of Science by: publishing results of scientific investigations in its Journal and Proceedings; conducting monthly meetings; organising summer science schools for senior secondary school students; awarding prizes and medals; and by liason with other scientific societies. Special meetings are held for: the Pollock Memorial Lecture in Physics and Mathematics, the Liversidge Research Lecture in Chemistry, the Clarke Memorial Lecture in Geology, Zoology and Botany, and the Poggendorf Lecture in Agricultural Science. 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Responsibility for interpretations, opinions, reproductions and data published on behalf of authors rests with the relevant authors, not with the Royal Society of New South Wales. i i i i i i \Main" | 2003/4/21 | 18:25 | page 57 | #3 i i Journal & Proceedings of the Royal Society of New South Wales, Vol. 135, p. 57{71, 2003 ISSN 0035-9173/03/020057{15 $4.00/1 The 33rd Liversidge Lecture for the Royal Society of NSW Dietary Chemicals and Brain Function graham a. r. johnston Abstract Phytochemicals in our diet may play a vital role in maintaining the brain's chemical balance by influencing the function of receptors for the major inhibitory neurotransmitter GABA. The flavonoids apigenin and epigallocatechin gallate, found in chamomile and green tea respectively, influence the way in which GABA receptors are modulated by drugs such as di- azepam. Resveratrol, a flavonoid-like polyphenol found in red wine, acts on a subtype of GABA receptors consistent with its action as a cognitive enhancer. Bilobalide from Ginkgo biloba, a herb used in cognitive therapy, also influences GABA receptors. α-Thujone, a terpenoid in the alcoholic beverage Absinthe, acts in a similar manner to bilobalide on GABA receptors. ( )-Borneol and other terpenoids from Valerian, a herb used to promote sleep, enhance the effects of GABA. The effects of these phytochemicals on GABA receptors are consistent with the overall actions of the beverages and herbal preparations that contain them, thus providing a rational basis for the use of these beverages and herbal preparations. These studies provide evidence that chemicals in our diet may influence brain function in a positive way. The chemical nature of these substances may lead to the development of new therapeutic agents for the treatment of anxiety, epilepsy, memory disorders and insomnia. Keywords: Brain function, chemicals, diet, balance, dosage THE BRAIN'S CHEMICAL over excited brain (as in Figure 1) that can be BALANCE manifested as anxiety, agitation, exhilaration, convulsions and death. On the other hand, an Two simple chemicals, glutamic acid and excess of inhibition over excitation can be man- GABA (Figure 1), are responsible for most of ifested by depression, anaesthesia, coma and the communication between nerve cells in the death. The particular manifestations of such brain. Indeed, at a very simple level, brain func- imbalances in the brain depend on what neu- tion may be thought of as a balance between ronal circuitry is involved. excitation mediated by glutamic acid and inhi- bition mediated by GABA. Ethanol is an example of a chemical that All nerve cells in the brain have receptors acts on both sides of the brain's chemical bal- for glutamic acid and GABA. Some 40% of ance. The CNS depression that results from in- nerve cells release glutamic acid as an excita- gestion of ethanol is due to a reduction in excita- tory neurotransmitter, while a different 40% re- tion mediated by glutamic acid acting on a sub- lease GABA as an inhibitory neurotransmitter. type of glutamate receptors known as NMDA The balance between these two chemical trans- receptors and to an enhancement of inhibition mitters is vital to normal brain function. An mediated by GABA acting on GABAA recep- excess of excitation over inhibition results in an tors. i i i i i i \Main" | 2003/4/21 | 18:25 | page 58 | #4 i i 58 JOHNSTON H2N COOH H2N COOH COOH GABA Inhibition + ((( Glutamic acid ((( (((( ((( Exitation (((( (((( ¢B + ((( (((( ¢ B ¢ B Figure 1: The brain's chemical balance between excitation mediated by the major excitatory neurotransmitter, glutamic acid, and inhibition mediated by the major inhibitory neurotransmitter, GABA. GABA RECEPTORS oocytes from the South African frog, Xenopus laevis following injection of either DNA or RNA GABA (whose name is derived from the old cloned from human brain and coding for par- chemical name, γ-aminobutyric acid) acts on ticular GABA receptor protein subunits. These three main types of receptor to influence brain oocytes have the necessary cellular machinery to function. GABAA and GABAC receptors are make the human proteins and assemble them on fast acting receptors that belong to the group the surface of the oocytes as functional GABA of receptors called ligand-gated ion channels receptors. The oocytes are approximately one (LGICs) (Chebib and Johnston, 2000). GABA millimetre in diameter and readily penetrated acts as the ligand gating these receptors to by glass microelectrodes. Using 2-electrode open channels specific for chloride ions, allowing voltage clamp methodology, the effects of chem- these ions to flow rapidly into nerve cells mak- icals on the function of these GABA receptors ing them more negative and thus harder to ex- may be assessed in a convenient quantitative cite. GABAB receptors act more slowly, induc- manner. For example, using recombinant recep- ing metabolic changes in nerve cells and belong tor technology, the effects of anti-anxiety agents to the group of receptors called G-protein cou- such as diazepam (Valium) on GABA recep- pled receptors (GPCRs) (Bowery et al. 1997). tors can be easily shown to be restricted to a specific sub-group of GABAA receptors. The The study of GABA receptors has been rev- technology is not restricted to the study of pure olutionised by the introduction of recombinant chemicals { relatively crude mixtures of chem- receptor technology whereby receptors cloned icals can be studied, for example to follow the from human brain are expressed in cells that do purification of chemicals acting on GABA re- not normally express such receptors (Barnard et ceptors from extracts of herbal products. al. 1998). The recombinant receptors so formed may be studied in relative isolation using stan- dard electrophysiological methodology. Since FLAVONOIDS AND TERPENOIDS all GABA receptors are made up of protein sub- units, recombinant receptors of known subunit Flavonoids are polyphenolic chemicals widely composition may be studied. distributed in the plant kingdom particularly The most common way to study recombi- in flowering plants. Flavonoids are responsi- nant GABA receptors is to express them in ble for many of the brilliant colours of fruits i i i i i i \Main" | 2003/4/21 | 18:25 | page 59 | #5 i i DIETARY CHEMICALS AND BRAIN FUNCTION 59 and vegetables and are important constituents van, epigallocatechin gallate (Figure 2). of red wine, green tea and many herbal prepa- Terpenoids are also widespread in plants, es- rations (Aherne and O'Brien, 2002).