neurogenesis
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This review focuses on the relationship between psychotropic drugs and adult hippocampal neurogenesis. Adult neurogenesis is important for learning and memory, as well as for depression and anxiety. There is some evidence that chronic treatment with opiates, stimulants and entactogens decreases neurogenesis and consequently impairs cognitive function, as well as inducing depressive-like behaviour in animals during drug withdrawal. On the other hand, NMDA receptor antagonists increase neurogenesis, but negatively affect cognitive function and have an antidepressant-like profile. We suggest that drug-induced changes in neurogenesis have a greater and more concise effect on emotive state reflecting the direction of influencing new cells proliferation than the performance of cognitive tasks. In this review we provide some evidence for this assumption.
- MeSH
- emoce účinky léků fyziologie MeSH
- hipokampus cytologie účinky léků fyziologie MeSH
- kognice účinky léků fyziologie MeSH
- lidé MeSH
- neurogeneze účinky léků fyziologie MeSH
- psychotropní léky farmakologie MeSH
- stárnutí účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Neurogeneze představuje proces spojený s tvorbou nových nervových buněk. Tento přehledný článek přináší shrnutí vlivu psychotropnich látek na neurogenezi v dospělém savčím hipokampu. Opiáty, stimulancia a opakovaná aplikace 3,4-metylendioxymetamfetaminu snižují proliferaci progenitorových buněk, některé látky navíc ovlivňují i buněčnou maturaci (morfm) a přežívání (morfin, metamfetamin, 3,4-metylendioxymetamfetamin). Hipokampální neurogeneze není pravděpodobně ovlivněna podáním halucinogenů (diethylamid kyseliny lysergové, 2,5-dimetoxy-4-iodoamfetamin) ani vysokými dávkami delta-9-tetrahydrocannabinolu. Antagonisté N-methyl-D-aspartátového receptoru mají naopak podpůrný vliv na neurogenezi, který je pravděpodobně zprostředkován zvýšením hladin mozkového neurotropniho faktoru.
Neurogenesis is a process associated with the formation of new nerve cells. This review summarizes the influence of psychotropic drugs on neurogenesis in the adult mammalian hippocampus. Opiates, stimulants and chronic 3,4-methylenedioxymethamphetamine administration decrease proliferation of progenitor cells; some drugs also influence the maturation (morphine) and survival (mo rphine, methamphetamine, 3,4-methylenedioxymethamphetamine). Hippocampal neurogenesis does not seem to be affected by the administra- tion of hallucinogens (lysergic acid diethylamide, 2,5-dimethoxy-4-iodoamphetamine) or high doses of delta-9-tetrahydrocannabin ol. On the other hand, antagonists of N-methyl-D-aspartate receptor have stimulating effect on neurogenesis, which is probably mediate d by increased levels of brain derived neurotrophic factor.
- Klíčová slova
- opiáty, MDMA,
- MeSH
- fencyklidin MeSH
- gyrus dentatus fyziologie MeSH
- halucinogeny MeSH
- hipokampus * růst a vývoj účinky léků MeSH
- ketamin MeSH
- kokain MeSH
- lidé MeSH
- N-methyl-3,4-methylendioxyamfetamin MeSH
- neurogeneze * fyziologie účinky léků MeSH
- potkani Wistar MeSH
- psychotropní léky * aplikace a dávkování terapeutické užití MeSH
- receptory N-methyl-D-aspartátu antagonisté a inhibitory MeSH
- savci MeSH
- stimulancia MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
The function of adult neurogenesis in the dentate gyrus is not yet completely understood, though many competing theories have attempted to explain the function of these newly-generated neurons. Most theories give adult neurogenesis a role in aiding known hippocampal/dentate gyrus functions. Other theories offer a novel role for these new cells based on their unique physiological qualities, such as their low excitability threshold. Many behavioral tests have been used to test these theories, but results have been inconsistent and often contradictory. Substantial variability in tests and protocols may be at least partially responsible for the mixed results. On the other hand, conflicting results arising from the same tests can serve as aids in elucidating the function of adult neurogenesis. Here, we offer a hypothesis that considers the cognitive nature of tasks commonly used to assess the function of adult neurogenesis, and introduce a dichotomy between tasks focused on discrimination vs. generalization. We view these two aspects as opposite ends of the continuous spectrum onto which traditional tests can be mapped. We propose that high neurogenesis favors behavioral discrimination while low adult neurogenesis favors behavioral generalization of a knowledge or rule. Since many tasks require both, the effects of neurogenesis could be cancelled out in many cases. Although speculative, we hope that our view presents an interesting and testable hypothesis of the effect of adult neurogenesis in traditional behavioral tasks. We conclude that new, carefully designed behavioral tests may be necessary to reach a final consensus on the role of adult neurogenesis in behavior.
- MeSH
- diskriminační učení fyziologie MeSH
- hipokampus cytologie růst a vývoj MeSH
- lidé MeSH
- neurogeneze fyziologie MeSH
- prostorové chování fyziologie MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Sphingolipids (SLs) are important signaling molecules and functional components of cellular membranes. Although SLs are known as crucial regulators of neural cell physiology and differentiation, modulations of SLs by environmental neurotoxicants in neural cells and their neuronal progeny have not yet been explored. In this study, we used in vitro models of differentiated neuron-like cells, which were repeatedly exposed during differentiation to model environmental toxicants, and we analyzed changes in sphingolipidome, cellular morphology and gene expression related to SL metabolism or neuronal differentiation. We compared these data with the results obtained in undifferentiated neural cells with progenitor-like features. As model polychlorinated organic pollutants, we used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3'-dichlorobiphenyl (PCB11) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153). PCB153 revealed itself as the most prominent deregulator of SL metabolism and as potent toxicant during early phases of in vitro neurogenesis. TCDD exerted only minor changes in the levels of analysed lipid species, however, it significantly changed the rate of pro-neuronal differentiation and deregulated expression of neuronal markers during neurogenesis. PCB11 acted as a potent disruptor of in vitro neurogenesis, which induced significant alterations in SL metabolism and cellular morphology in both differentiated neuron-like models (differentiated NE4C and NG108-15 cells). We identified ceramide-1-phosphate, lactosylceramides and several glycosphingolipids to be the most sensitive SL species to exposure to polychlorinated pollutants. Additionally, we identified deregulation of several genes related to SL metabolism, which may be explored in future as potential markers of developmental neurotoxicity.
- MeSH
- buněčná diferenciace účinky léků MeSH
- buněčné linie MeSH
- látky znečišťující životní prostředí toxicita MeSH
- neurogeneze účinky léků MeSH
- neurony účinky léků metabolismus MeSH
- neurotoxické syndromy etiologie genetika MeSH
- polychlorované bifenyly farmakologie toxicita MeSH
- polychlorované dibenzodioxiny toxicita MeSH
- sfingolipidy metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Hypothalamic Adult Neurogenesis (hAN) has been implicated in regulating energy homeostasis. Adult-generated neurons and adult Neural Stem Cells (aNSCs) in the hypothalamus control food intake and body weight. Conversely, diet-induced obesity (DIO) by high fat diets (HFD) exerts adverse influence on hAN. However, the effects of anti-obesity compounds on hAN are not known. To address this, we administered a lipidized analogue of an anti-obesity neuropeptide, Prolactin Releasing Peptide (PrRP), so-called LiPR, to mice. In the HFD context, LiPR rescued the survival of adult-born hypothalamic neurons and increased the number of aNSCs by reducing their activation. LiPR also rescued the reduction of immature hippocampal neurons and modulated calcium dynamics in iPSC-derived human neurons. In addition, some of these neurogenic effects were exerted by another anti-obesity compound, Liraglutide. These results show for the first time that anti-obesity neuropeptides influence adult neurogenesis and suggest that the neurogenic process can serve as a target of anti-obesity pharmacotherapy.
Adult neurogenesis in the dentate gyrus adds a substantial number of new functional neurons to the hippocampus network in rodents. To date, however, the function of these new granule cells remains unclear. We conducted an experiment to assess the contribution of adult neurogenesis in the dentate gyrus to acquisition and reversal learning in a task that predominantly requires generalization of a rule. Young adult male Long-Evans rats were repeatedly administered either a cytostatic temozolomide or saline for a period of four weeks (3 injections per week). Post treatment, animals were injected with bromodeoxyuridine to quantify adult neurogenesis in the dentate gyrus. For behavioral assessment we used hippocampus-dependent active place avoidance with reversal in a Carousel maze. Animals first learned to avoid a 60° sector on the rotating arena. Afterwards, sector was relocated to the opposite side of the rotating arena (reversal). The administration of temozolomide significantly improved the reversal performance compared to saline-treated rats. Our results suggest a significant, level-dependent, improvement of reversal learning in animals with reduced adult neurogenesis in hippocampus.
- MeSH
- alkylační protinádorové látky farmakologie MeSH
- dakarbazin analogy a deriváty farmakologie MeSH
- gyrus dentatus účinky léků MeSH
- krysa rodu rattus MeSH
- neurogeneze účinky léků MeSH
- neurony účinky léků MeSH
- potkani Long-Evans MeSH
- prostorové učení účinky léků MeSH
- reverzní učení účinky léků MeSH
- učení vyhýbat se účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The dentate gyrus of the hippocampus is one of the few places in the brain where neurogenesis occurs in adulthood. Nowadays, an increasing number of children and young adults are affected by hypertension, one of the factors in the development of cerebrovascular diseases and age-related cognitive deficits. Since these cognitive deficits are often hippocampus-dependent, it is possible that hypertension exerts this effect via decreasing adult neurogenesis which has been shown to be essential for a range of cognitive tasks. We used spontaneously hypertensive rats, which develop hypertension in the first weeks of life. Half of them were treated with the antihypertensive drug captopril. We found that the drug-induced lowering of blood pressure in this period did not affect the rate of adult neurogenesis. In a second experiment, we used another animal model of hypertension - salt-sensitive and salt-resistant strains of Dahl rats. A high-salt diet induces hypertension in the salt-sensitive strain, but not in the salt-resistant strain. The high-salt diet led to salt-induced hypertension, but did not affect the level of adult neurogenesis in the dentate gyrus of the hippocampus. We conclude that hypertension does not significantly affect the rate of hippocampal neurogenesis in young adult rats.
- MeSH
- hipokampus patologie fyziologie MeSH
- hypertenze patologie patofyziologie MeSH
- krevní tlak fyziologie MeSH
- krysa rodu rattus MeSH
- náhodné rozdělení MeSH
- neurogeneze fyziologie MeSH
- potkani inbrední Dahl MeSH
- potkani inbrední SHR MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cieľom práce bolo skúmať účinok raného environmentálneho stresu na postnatálnu neurogenézu v čuchovom systéme potkana. Naše výsledky ukázali, že senzorická deprivácia zvierat počas skorého postnatálneho obdobia vyvoláva výrazne kvantitatívne a morfologické zmeny v dráhe, ktorou migrujú bunky do bulbus olfactorius. Sledované zmeny sa líšili v závislosti od dĺžky trvania senzorickej deprivácie.
The aim of our study was to investigate effects of early environmental stress on postnatal neurogenesis in the rat olfactory system. Our results show that sensory deprivation of animals in early postnatal periods may induce significant quantitative and morphological changes in the neurogenic pathway of the olfactory system. The observed changes differed in relation to the duration of sensory deprivation.
- Klíčová slova
- postnatálna neurogenéza, ranný stres, proliferácia, odumieranie buniek, diferenciácia buniek,
- Publikační typ
- abstrakty MeSH
Processes of adult neurogenesis can be influenced by environmental factors. Here, we investigated the effect of microwave radiation (MWR) on proliferation and cell dying in the rat rostral migratory stream (RMS) - a migration route for the neuroblasts of the subventricular zone. Adult and juvenile (two weeks old) rats were exposed to a pulsed-wave MWR at the frequency of 2.45 GHz for 1 or 3 h daily during 3 weeks. Adult rats were divided into two groups: without survival and with two weeks survival after irradiation. Juvenile rats survived till adulthood, when were tested in the light/dark test. Proliferating cells in the RMS were labeled by Ki-67; dying cells were visualized by Fluoro-Jade C histochemistry. In both groups of rats irradiated as adults we have observed significant decrease of the number of dividing cells within the RMS. Exposure of juvenile rats to MWR induced only slight decrease in proliferation, however, it strikingly affected cell death even two months following irradiation. In addition, these rats displayed locomotor hyperactivity and decreased risk assessment in adulthood. Our results suggest that the long-lasting influence of radiation is manifested by affected cell survival and changes in animals´ behavior.
Subventrikulárna zóna (SVZ) je miestom postnatálnej neurogenézy. Bunky vznikajúce v SVZ migrujú rostrálnou migračnou dráhou (RMS) do bulbus olfactorius (BO), ktoré je zároveň primárnym čuchovým centrom. Cieľom tejto práce bolo skúmať vplyv vôňami obohateného prostredia na neurogenézu u potkanov. Porovnávali sme bunkové zloženie RMS potkanov, ktorých sme čuchovo stimulovali s RMS kontrolných potkanov, a zistili sme, že vôňami obohatené prostredie pozitívne ovplyvnilo bunkovú proliferáciu a zároveň spôsobilo pokles odumierajúcich buniek. Zistili sme tiež, že diferencované (nitrergické bunky) sa objavujú u čuchovo Stimulovaných zvierat vt včasnejšie ako u kontrolných zvierat, avšak na druhej strane ich počet je v porovnaní s kontrolnými zvieratami nižší.
The subventricular zone (SVZ) is the main niche of postnatal neurogenesis. The cells born in the SVZ migrate by the rostral migratory stream (RMS) toward the olfactory bulb, which is concurrently the first relay on the sensory pathway. The aim of this study was to exa- mine influence of odor enriched environment on neurogenesis in rats. We compared cell composition of the RMS of olfactory stimulated rats with control matches. We found that odor enriched environment positively influenced cell proliferation and concurrently caused decrease of dying cells. We have also found that differentiated (nitrergic) cells appeared in the RMS of olfactory stimulated rats earlier then in control rats, but on the other hand their number was in comparison with control rats reduced.
- Klíčová slova
- čuchová stimulácia, neurogenéza, rostrálna migračná dráha,
- Publikační typ
- abstrakty MeSH
