The neurotrophic and neuroprotective effects of psychotropic agents
- PMID: 19877500
- PMCID: PMC2804881
- DOI: 10.31887/DCNS.2009.11.3/jhunsberger
The neurotrophic and neuroprotective effects of psychotropic agents
Abstract
Accumulating evidence suggests that psychotropic agents such as mood stabilizers, antidepressants, and antipsychotics realize their neurotrophic/neuroprotective effects by activating the mitogen activated protein kinase/extracellular signal-related kinase, PI3-kinase, and wingless/glycogen synthase kinase (GSK) 3 signaling pathways. These agents also upregulate the expression of trophic/protective molecules such as brain-derived neurotrophic factor, nerve growth factor, B-cell lymphoma 2, serine-threonine kinase, and Bcl-2 associated athanogene 1, and inactivate proapoptotic molecules such as GSK-3. They also promote neurogenesis and are protective in models of neurodegenerative diseases and ischemia. Most if not all, of this evidence was collected from animal studies that used clinically relevant treatment regimens. Furthermore, human imaging studies have found that these agents increase the volume and density of brain tissue, as well as levels of N-acetyl aspartate and glutamate in selected brain regions. Taken together, these data suggest that the neurotrophic/neuroprotective effects of these agents have broad therapeutic potential in the treatment; not only of mood disorders and schizophrenia, but also neurodegenerative diseases and ischemia.
La evidencia acumulada sugiere que los agentes psicotrópicos como los esiabilizadores del ánimo, los antidepresivos y los antipsicóticos producen sus efectos neurotróficos/neuroproiectores mediante la activación de la quinasa relacionada con la señal de la proteinquinasalextracelular activada por mitógen o, la quinasa PI3 y las vías de señates de la winglesslglicógeno sintelasa quinasa 3 (GSK), Estos agentes también regulan hacia arriba la expresion de moléculas tróficaslprotecioras como el factor neurotrófico cerebral, el factor de crecimiento neural, la proteina 2 del linfoma de células B, la quinasa serina-treonina y el atanogen 1 asociado a Bcl-2, e inactivan moléculas proapoptóticas como la GSK-3. Ellos también promueven la neurogénesis y son protectores en modelos de enfermedades neurodegeneratives e isquemia. La mayor parte, sino toda esta evidencia se recolectó a partir de estudios animales que utilizaron esquemas terapéuticos clínicamente relevantes. Además, en humanos los estudios de imágenes han encontrado que estos fármacos aumentan el volumen y la densidad del tejido cerebral, como también los niveles de N-acetil aspartato y glutamato en determinadas regiones cerebrales. Tomados en conjunto, estos datos sugieren que los efectos neurotróficoslneuroprotectores de estos fármacos tienen un gran potencial terapéutico en el tratamiento no sólo de los trastornos del ánimo y de la esquizofrenia, sino que también en enfermedades neurodegenerativas y en la isquemia.
D'après un nombre croissant d'arguments, les psychotropes, comme les régulateurs de l'humeur, les antidépresseurs et les antipsychotiques, exercent leurs effets neuroirophiques et neuroprotecteurs en activant 3 voies de signalisation: la MAP (mitogen activated protein)/ERK (extracellular signal-related) kinase, la kinase PI3 et la Wnt/GSK (win gless/kinase glycogène synthase). Ces voies régulent également positivement l'expression des molécules irophiques/proiecirices comme le BDNF (brain-derived neurotrophic factor), le NGF (nerve growth factor), la protéine BCL2 (B-cell lymphoma 2), la kinase sérine-thréonine et le BAG-1 (aihanogène 1 associé à BCL-2), et des molécules proapoptotiques inactivées comme la GSK-3. Elles favorisent aussi la neurogenèse et exercent un effet protecteur dans les maladies neurodegeneratives et l'ischémie. La plupart de ces preuves, si ce n'est toutes, sont issues d'études animales utilisant des schémas thérapeutiques cliniquement pertinents. De plus, des études d'imagerie sur l'homme ont montré que ces agents augmentaient le volume et la densité du tissu cérébral ainsi que les taux de N-acétyl aspartate et de glutamate dans les régions cérébrales sélectionnées. Au total, ces données suggèrent que leurs effets neuroirophiques/neuroprotecteurs ont un potentiel thérapeutique large non seulement dans les troubles de l'humeur et la schizophrénie mais aussi dans les maladies neurodegeneratives et l'ischémie.
Figures
![Figure 1.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3181924/bin/DialoguesClinNeurosci-11-333-g001.gif)
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