Unconventional neurotransmitters, neurodegeneration and neuroprotection

Abstract

Neurotransmitters are also involved in functions other than conventional signal transfer between nerve cells, such as development, plasticity, neurodegeneration, and neuroprotection. For example, there is a considerable amount of data indicating developmental roles for the glutamatergic, cholinergic, dopaminergic, GABA-ergic, and ATP/adenosine systems. In this review, we discuss the existing literature on these "new" functions of neurotransmitters in relation to some unconventional neurotransmitters, such as the endocannabinoids and nitric oxide. Data indicating both transcriptional and post-transcriptional modulation of endocannabinoid and nitrinergic systems after neural lesions are discussed in relation to the non-conventional roles of these neurotransmitters. Knowledge of the roles of neurotransmitters in brain functions other than information transfer is critical for a more complete understanding of the functional organization of the brain and to provide more opportunities for the development of therapeutical tools aimed at minimizing neuronal death. The endocannabinoid system Endocannabinoids are defined as endogenous ligands of the cannabinoid receptors CB1 and CB2 (1). The basal levels of endocannabinoids are similar in different areas of the brain, including the brainstem, striatum, hippocampus, neocortex, diencephalon, and cerebellum. However, provocative data indicate that there is no direct correlation between the concentration of the endocannabinoids and the expression of the CB1 receptor, which suggests that endocannabinoids could also be involved in other neurotransmitter systems. Actually, it is also known that these compounds can directly modulate several other receptors, such as the serotonergic 5-HT 2 and 5-HT 3 receptors, the glutamatergic N-methyl-D-aspartate (NMDA) receptor, and the transient receptor potential vanilloid type 1 (TRPV1) (2).The first endocannabinoid to be isolated was N-arachidonoylethanolamine, or anandamide, an amide of arachidonic acid with ethanolamine. In 1995, 2-arachidonoylglycerol (2-AG) was discovered, an ester of arachidonic acid with glycerol, which is the most abundant cannabinoid ligand in the central nervous system. Since then, several other lipids, all derived from arachidonic acid, have been shown to modulate the cannabinoid receptors, such as 2-arachidonoylglycerol ether (noladin ether), O-arachidonoylethanolamine (virodhamina), and N-arachidonoyldopamine (3).Both anandamide and 2-AG are synthesized on demand under neuronal stimulation. Anandamide is produced by the enzymes N-acyl-phosphatidylethanolaminehydrolyzing-phospholipase D and is degraded by fatty acid amide hydrolase. 2-AG is synthesized by diacylglycerol

Exercise improves hemodynamic profiles and increases red blood cell concentrations of purine nucleotides in a rodent model

“…The importance of adenosine and ATP in regulating many biological functions has long been recognized, especially for their effects on the cardiovascular system [Ingwall, 2009;Cohen and Downey, 2008;Moens et al 2005;Burnstock, 2002;Linden, 2001;Oxhorn et al 2000;Shiode et al 1998;Ely and Berne, 1992;Olsson and Pearson, 1990]. It is known that adenosine and ATP are key factors in regulation of coronary blood flow [Tune et al 2002;Oxhorn et al 2000;Berne, 1980], inhibiting platelet aggregation [Gerlach et al 1987], protection of myocardium [Cohen and Downey, 2008;Obata, 2002], neuromodulation [Burnstock, 2009a[Burnstock, , 2009bFranco et al 2009;Leonelli et al 2009;Ralevic, 2009], modulating tissue necrosis [Burnstock, 2002], ischemic preconditioning [Das and Das, 2008;Donato and Gelpi, 2003;Funahashi, 2003;de Jong et al 2000], immunomodulation [McCallion et al 2004], energy metabolism [Ingwall, 2009;Porkka-Heiskanen et al 2003], and perhaps other functions as well (e.g. pain mediation) which maintain the homeostasis of the cardiovascular system.…”

Candidate biomarkers of multiple system atrophy in cerebrospinal fluid

“…Neurotransmitters function as chemical messengers that transfer signals between neurons and are also involved in the development, plasticity, neurodegeneration, and neuroprotection of the nervous system (Leonelli et al, 2009). The levels of their metabolites may reflect the neurons' metabolism and function.…”

O ciclo da vesícula sináptica, espinhos dendríticos e a transdução de sinal

“…16,17,19 Além dos neurotransmissores clássicos têm-se estudado novos neurotransmissores como o ATP, o óxido nítrico e os endocanabinóides. 20,21,22 Os endocanabinóides atuam como ligantes endógenos do receptor canabinóide CB1 que é o receptor metabotró-pico mais abundante no encéfalo de mamíferos. Ao serem ativados, os receptores CB1 bloqueiam o influxo de Ca ++ e causam o bloqueio de canais dependentes de voltagem do tipo L. Como o influxo de cálcio é uma etapa importante para a liberação de vesículas de todos os neurotransmissores, o sistema canabinóide endógeno pode atuar como mensageiro inibitório de diversas sinapses do SNC.…”