Fernando Garcia de Mello

Fernando Garcia de Mello (July 23, 1944 - ) is a Brazilian neuroscientist, in which he developed works in Neurochemistry, and professor at the Federal University of Rio de Janeiro. Mello is undergraduated in Medicine,[1] graduated in Biophysics, has a PhD in Biophysics and a post-doc by the National Institutes of Health, where his advisor was Marshall Warren Nirenberg, a famous scientist known for the discovery of the genetic code and later developed works in neuroscience.[2]

Garcia de Mello became known for his pioneers works in neurochemistry and for the consolidation of this field in Latin America, where he was responsible for the qualification of several neurochemistry groups. Fernando Mello was awarded the Medal Neuroscience from Brazilian Society for Neuroscience and Behavior and was honored with a symposium promoted by the American Society for Neurochemistry for his contributions to the area.[3]

Research

• The GABAergic system

Fernando Mello started his career in neurochemistry studying aspects of the GABAergic system at National Institute of Health, to do so, he used the retina as a model to study it, since this tissue has all the neurochemicals from the nervous system and its morphology is well characterized. Mello discovered that GABA levels didn't match the levels of Glutamate decarboxylase (GAD), the enzyme responsible for the synthesis of this neurotransmitter, during the first days of development. To explain that, Mello hypothesized that during this initial period of development, there was another biosynthesis pathway for GABA besides the one GAD-dependent. By the time, some works showed that bacterias are able to synthesize GABA from Putrescine via Monoamine oxidase. In 1976 he published a paper showing that this pathway actually occurred in the beginning of development, proving his hypothesis.[4]

After that, Mello did an immunoreactivity for GAD and GABA in the embryonic retina, and discovered that GABA can be detected as early as embryonic day 6 of avian development, but GAD containing cells were not detected until day 10. Therefore, in December 1990, Mello et al. showed that in early development, there is GABA in the tissue before any expression of the enzyme responsible for its synthesis, showing that putrescine was probably the main pathway in the early development stages.[5]

Another of the prestigious researches from Fernando Garcia de Mello was done along with professor José Luiz Martins do Nascimento, from the Federal University of Pará. It is well known that neurotransmitters could be released by Exocytosis in a Calcium-dependent manner and it was believed that this is the main pathway for neurotransmitter release in the Central Nervous System. However, in 1985, Mello and Nascimento published in the Journal of Neurochemistry[6] their findings of a GABA release mechanism that is calcium-independent but sodium-dependent. Through a series of experimental procedures, they discovered that in the retina, GABA release was almost exclusively done through reversal mode of GABA transporter (GAT) and not by exocytosis.

• Excitatory amino acids

Mello's group was very concerned with excitatory amino acids neurochemistry. Along with his partner Maria Christina Fialho de Mello, Fernando found that Glutamate (neurotransmitter) is able to induce GABA release in the retina[7] and that could be a protection mechanism against Excitotoxicity, in which the system tries to compensate the excitation promoted by glutamate through the release of the main inhibitory neurotransmitter: GABA.

Since the last century, it is proposed a cholinergic hypothesis for Alzheimer's disease due to several works showing a decrease in the enzyme's activity responsible for Acetylcholine synthesis: Choline acetyltransferase (ChAT). Although this phenomenum was stablished in the literature, it was unknown how this decrease in the enzyme's activity occurred. In 2002, Fernando Mello published in the Journal of Neurochemistry[8] a research showing that glutamate, the main excitatory amino acid in the nervous system and one of the possible dysregulated signaling molecules in Alzheimer, is able to decrease the activity of ChAT, elucidating a possible mechanism for the cholinergic dysfunction in Alzheimer's disease.

One of the main questions in neurochemistry concerned D-aspartate (D-Asp). It was known that it's a NMDA receptor agonist and that during retina's development, there is a high increase in the release of this molecule, but this release was not mediated neither by Exocytosis neither by reversal of transporter, the two main pathways for neurotransmitter release. In 2011, Mello et al. brought to light that D-Aspartate release was done by an exchange with glutamate through one of the High-Affinity Sodium-Dependent Excitatory Amino Acids Transporters (EAAT's).[9]

Carlos Chagas Filho Institute of Biophysics

Fernando Garcia de Mello was one of the greatests contributors to the development of one of the most renowned neuroscience's centers in the world: Carlos Chagas Filho Institute of Biophysics. Mello was responsible for the consolidation of various groups of neurochemistry in Brazil.

He was director of the Institute twice[10] and coordinated the Laboratory of Neurochemistry until 2015, when he retired and gave his chair to Ricardo Augusto de Melo Reis.

References

  1. ↑ "Fernando Garcia de Mello - Emérito | Biofisica UFRJ". www.biof.ufrj.br (in Portuguese). Retrieved 2018-04-19.
  2. ↑ "Currículo do Sistema de Currículos Lattes (Fernando Garcia de Mello)". lattes.cnpq.br (in Portuguese). Retrieved 2018-09-26.
  3. ↑ "Fernando Garcia de Mello TWAS" (PDF).
  4. ↑ Mello, F. G.; Bachrach, U.; Nirenberg, M. (October 1976). "ORNITHINE AND GLUTAMIC ACID DECARBOXYLASE ACTIVITIES IN THE DEVELOPING CHICK RETINA". Journal of Neurochemistry. 27 (4): 847–851. doi:10.1111/j.1471-4159.1976.tb05145.x. ISSN 0022-3042.
  5. ↑ "Developmental immunoreactivity for GABA and GAD in the avian retina: possible alternative pathway for GABA synthesis". Brain Research. 532 (1–2): 197–202. 1990-11-05. doi:10.1016/0006-8993(90)91760-E. ISSN 0006-8993.
  6. ↑ Nascimento, Jose Luiz M.; Mello, Fernando G. (December 1985). "Induced Release of ?-Aminobutyric Acid by a Carrier-Mediated, High-Affinity Uptake of L-Glutamate in Cultured Chick Retina Cells". Journal of Neurochemistry. 45 (6): 1820–1827. doi:10.1111/j.1471-4159.1985.tb10539.x. ISSN 0022-3042.
  7. ↑ "l-Glutamate evoked release of GABA from cultured avian retina cells does not require glutamate receptor activation". Brain Research. 443 (1–2): 166–172. 1988-03-08. doi:10.1016/0006-8993(88)91609-5. ISSN 0006-8993.
  8. ↑ Loureiro-dos-Santos, Nelson E.; Reis, Ricardo A. M.; Kubrusly, Regina C. C.; De Almeida, Olga M. M. S.; Gardino, Patricia F.; De Mello, Maria C. F.; De Mello, Fernando G. (2001-12-20). "Inhibition of choline acetyltransferase by excitatory amino acids as a possible mechanism for cholinergic dysfunction in the central nervous system". Journal of Neurochemistry. 77 (4): 1136–1144. doi:10.1046/j.1471-4159.2001.00330.x. ISSN 0022-3042.
  9. ↑ "Exchange of extracellular l-glutamate by intracellular d-aspartate: The main mechanism of d-aspartate release in the avian retina". Neurochemistry International. 58 (7): 767–775. 2011-06-01. doi:10.1016/j.neuint.2011.03.001. ISSN 0197-0186.
  10. ↑ "Direção | Biofisica UFRJ". www.biof.ufrj.br (in Portuguese). Retrieved 2018-04-19.
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