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
- Emotions drug effects physiology MeSH
- Hippocampus cytology drug effects physiology MeSH
- Cognition drug effects physiology MeSH
- Humans MeSH
- Neurogenesis drug effects physiology MeSH
- Psychotropic Drugs pharmacology MeSH
- Aging drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review 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.
- Keywords
- opiáty, MDMA,
- MeSH
- Phencyclidine MeSH
- Dentate Gyrus physiology MeSH
- Hallucinogens MeSH
- Hippocampus * growth & development drug effects MeSH
- Ketamine MeSH
- Cocaine MeSH
- Humans MeSH
- N-Methyl-3,4-methylenedioxyamphetamine MeSH
- Neurogenesis * physiology drug effects MeSH
- Rats, Wistar MeSH
- Psychotropic Drugs * administration & dosage therapeutic use MeSH
- Receptors, N-Methyl-D-Aspartate antagonists & inhibitors MeSH
- Mammals MeSH
- Wakefulness-Promoting Agents MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review 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
- Discrimination Learning physiology MeSH
- Hippocampus cytology growth & development MeSH
- Humans MeSH
- Neurogenesis physiology MeSH
- Spatial Behavior physiology MeSH
- Age Factors MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Spinal cord injury is a devastating medical condition with no effective treatment. One approach to SCI treatment may be provided by stem cells (SCs). Studies have mainly focused on the transplantation of exogenous SCs, but the induction of endogenous SCs has also been considered as an alternative. While the differentiation potential of neural stem cells in the brain neurogenic regions has been known for decades, there are ongoing debates regarding the multipotent differentiation potential of the ependymal cells of the central canal in the spinal cord (SCECs). Following spinal cord insult, SCECs start to proliferate and differentiate mostly into astrocytes and partly into oligodendrocytes, but not into neurons. However, there are several approaches concerning how to increase neurogenesis in the injured spinal cord, which are discussed in this review. The potential treatment approaches include drug administration, the reduction of neuroinflammation, neuromodulation with physical factors and in vivo reprogramming.
- MeSH
- Cell Differentiation MeSH
- Humans MeSH
- Spinal Cord MeSH
- Neural Stem Cells * MeSH
- Neurogenesis MeSH
- Neurons MeSH
- Spinal Cord Injuries * therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review 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
- Cell Differentiation drug effects MeSH
- Cell Line MeSH
- Environmental Pollutants toxicity MeSH
- Neurogenesis drug effects MeSH
- Neurons drug effects metabolism MeSH
- Neurotoxicity Syndromes etiology genetics MeSH
- Polychlorinated Biphenyls pharmacology toxicity MeSH
- Polychlorinated Dibenzodioxins toxicity MeSH
- Sphingolipids metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study 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.
- MeSH
- Prolactin-Releasing Hormone pharmacology therapeutic use MeSH
- Hypothalamus MeSH
- Humans MeSH
- Mice MeSH
- Neurogenesis MeSH
- Neuropeptides * MeSH
- Obesity * drug therapy MeSH
- Body Weight MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
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
- Antineoplastic Agents, Alkylating pharmacology MeSH
- Dacarbazine analogs & derivatives pharmacology MeSH
- Dentate Gyrus drug effects MeSH
- Rats MeSH
- Neurogenesis drug effects MeSH
- Neurons drug effects MeSH
- Rats, Long-Evans MeSH
- Spatial Learning drug effects MeSH
- Reversal Learning drug effects MeSH
- Avoidance Learning drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article 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
- Hippocampus pathology physiology MeSH
- Hypertension pathology physiopathology MeSH
- Blood Pressure physiology MeSH
- Rats MeSH
- Random Allocation MeSH
- Neurogenesis physiology MeSH
- Rats, Inbred Dahl MeSH
- Rats, Inbred SHR MeSH
- Age Factors MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article 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.
- Keywords
- postnatálna neurogenéza, ranný stres, proliferácia, odumieranie buniek, diferenciácia buniek,
- Publication type
- Abstracts 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.
