Noradrenalina cz.2-trochę historii

Historia noradrenaliny to początek lat 90tych ubiegłego wieku. W 1991 roku po raz pierwszy powiązano ją z faktem starzenia się komórek. Wskazano wówczas, że pełni istotną rolę w naszej gotowości do działania (ADRENALINA!), cyklu spania i jego jakości, pamięci, zdolności do uczenia się, plastyczności mózgu i neuroprotekcji!

 

Wtedy też zaakceptowano jej rolę jako hormonu i neurotransmitera, który nie tylko pobudza nas do natychmiastowej gotowości ale odpowiada za przekazywanie impulsów nerwowych z jednego neuronu do kolejnego. Pokazano także istotny związek między jej funkcjonowaniem a tyrozyną, aminokwasem niezwykle istotnym dla funkcjonowania mózgu, a powiązanym z działaniem tarczycy i przysadki mózgowej. Jak się wtedy okazało jego brak wpływa na złe funkcjonowanie tarczycy, występuje wtedy jej niedoczynność, a co za tym idzie zmęczenie i wyczerpanie.

Kolejne badania pokazują silny związek noradrenaliny z funkcjami poznawczymi i demencji. Pod koniec 1994 roku rozpoczęto na szeroką skalę badania jej wpływu na zdolności poznawcze u zwierząt. Pod koniec tej dekady pojawiły się badania pokazujące istotną rolę noradrenaliny w leczeniu depresji. Od tego czasu zainteresowanie depresją i rolą noradrenaliny w jej osłabianiu wzrasta. Przypadkowe efekty z doświadczeń kreowanych w innych polach zainteresowań (podobnie jak to było z prozac-iem -lek antydepresyjny), pokazały prawdopodobny wpływ noradrenaliny na możliwości rozwoju, regeneracji komórek nerwowych, jak i samego mózgu. Badania zapoczątkowane na zwierzętach w latach 2000-2002 pozwoliły na lepsze poznanie roli funkcji poznawczych, ich reaktywności na czynniki stymulacyjne jak noradrenalina. Począwszy od 2006 roku substancja ta wchodzi w skład leków podawanych osobom dotkniętych różnymi formami autyzmu w celu stymulowania ich zachowań i walce z depresją.

W przypadku zespołu Downa, poszukuje się możliwości jej zastosowania w celu poprawy pamięci i uwagi. Zwraca się tutaj na fakt, iż tzw.LTP poprawia się w wyniku stosowania noradrenaliny u zwierząt. Były to efekty “uboczne” przy innych doświadczeniach, obecnie celowo rozwijane na myszach z modelem ZD.

Noradrenaline and cerebral aging
by
Jouvet M; Albarede JL; Lubin S; Meyrignac C
Laboratoire de Médecine Expérimentale,
Faculté de Médecine, Lyon.
Encephale, 1991 May-Jun, 17:3, 187-95
ABSTRACT

The central functions of norepinephrine (NE) are a recent discovery: regulation of alertness and of the wakefulness-sleep cycle, maintenance of attention, memory and learning, cerebral plasticity and neuro-protection. The anatomical, histological, biochemical and physiological properties of the central noradrenergic system: extreme capacity for ramification and arborization; slow conduction, non-myelinized axons with extrasynaptic varicosities producing and releasing NE; frequency of co-transmission phenomena, and; neuromodulation with fiber effect responsible for improvement in the signal over background noise ratio and selection of significant stimuli form a true interface between the outside world and the central nervous system, notably for the neocortex in the context of the cognitive treatment of information. This central noradrenergic system is involved in the neurophysiology and the clinical features of cerebral aging (ideation-motor and cognitive function slowing down, loss of behavioral adjustment), neuro-degenerative disorders (SDAT, Parkinson’s disease), certain aspects of depression and less obvious conditions (head injuries, sequelae of cerebrovascular accidents, sub-cortical dementia). The recent development of medications improving alertness (adrafinil, modafinil) with a pure central action and specifically noradrenergic, may contribute to an improvement in these multifactorial disorders.

 

Pharmacological manipulations of the
alpha 2-noradrenergic system. Effects on cognition
by
Coull JT
Drugs Aging 1994 Aug; 5(2):116-26
ABSTRACT

Electrophysiological and neurosurgical lesion studies with experimental animals have implicated the ascending dorsal noradrenergic bundle of the locus coeruleus system in cognitive process such as memory, learning and selective attention. However, it has also been suggested that noradrenaline (norepinephrine) is crucial in certain cognitive functions associated with the frontal lobes, particularly the prevention of distractibility by irrelevant stimuli. The alpha 2-receptors of the prefrontal cortex appear to be of particular importance in this respect. Studies with humans and experimental primates provide substantial support for this view. The aged primate brain is prone to degeneration of the locus coeruleus, as well as profound catecholamine depletion in the prefrontal cortex, and so is ideal for psychopharmacological investigation of the role of noradrenaline in frontal lobe function. Elderly monkeys show deficits in performance of the delayed response task, which can be reversed directly by both the mixed alpha 1/alpha 2-agonist clonidine, the more specific alpha 2-agonist guanfacine and also, indirectly, by the alpha 2-antagonist yohimbine. It is suggested that these results can be explained by an attenuation of the distracting properties of irrelevant stimuli following stimulation of noradrenergic activity. Conversely, distractibility is magnified whenever noradrenergic activity is reduced. This is supported by similar findings in psychopharmacological studies of healthy humans. The exception to this is when the locus coeruleus is likely to be firing, e.g. in times of stress or when novel stimuli are encountered. Clonidine attenuates locus coeruleus firing on such occasions, and so counteracts any beneficial (or deleterious) effects of stress on task performance. alpha 2-Adrenoceptor agents have little therapeutic value in patients with dementia of the Alzheimer’s type. However, they may have some clinical use in patients who have a cognitive symptomatology similar to that of patients who have received neurosurgical excisions to the frontal lobes, e.g. deficits in working memory, executive function or focused attention, with relative sparing of episodic short term memory. Patients with Korsakoff’s disease, attention deficit disorder or schizophrenia may benefit from treatment with alpha 2-agents. In particular, idazoxan has putative therapeutic effects in patients with a neurodegenerative disorder, namely dementia of frontal type.

http://www.brainexplorer.org/video/index.shtml

Predicting response:
noradrenaline reuptake inhibition
by
Montgomery S
Int Clin Psychopharmacol 1999 May; 14 Suppl 1:S21-6
ABSTRACT

For the past decade, the role of noradrenaline in depression has been somewhat neglected in favour of serotonin. This is largely because of the advent of the selective serotonin reuptake inhibitors, which have facilitated clinical and experimental observation of the roles of serotonin. Until now, no such tools have been available to study the noradrenergic system. However, the recent development of reboxetine, the first selective noradrenaline reuptake inhibitor, has allowed clinical investigation of the role of the noradrenergic system in different aspects of depressive disorders. In clinical trials, the use of reboxetine has shown that selective noradrenaline reuptake inhibition is an effective approach to alleviating depression. It is more effective than placebo and at least as effective as desipramine, imipramine and fluoxetine in the short term. In addition, its efficacy is maintained in patients with severe depression and in those receiving long-term maintenance treatment. Reboxetine is very well tolerated, as predicted from its pharmacological profile, having fewer anticholinergic side-effects than imipramine or desipramine. Compared with fluoxetine, patients treated with reboxetine experienced less nausea and sexual dysfunction, adverse events that are common among those taking selective serotonin reuptake inhibitors. Adverse events predicted by the neuroanatomy of the noradrenergic system, such as tremor and cardiovascular effects, occurred less frequently than expected. Clinical experience with reboxetine challenges our current knowledge of the role of noradrenaline in depression and questions existing evidence based on studies with noradrenergic tricyclic antidepressants. Selective noradrenaline reuptake inhibition, as exemplified by reboxetine, therefore offers a significant improvement in antidepressant pharmacotherapy, and an opportunity to increase our understanding of the role of noradrenaline in depression.

http://www.sciencedaily.com/releases/2009/04/090401145312.htm