Prenatal stress and drug exposure induce permanent alterations of the brain. Even though different brain structures are involved, alterations almost always refer to the hippocampus. The aim of this study was to investigate the excitability of hippocampal slices in low-magnesium epilepsy model of prenatally methamphetamine (MA, 5mg/kg sc.) or saline (sc., stress model) exposed animals in adult male rats. The second aim was to investigate, if a low dose of MA (1ml/kgs.c.) administered in adulthood changes the hippocampal activity of these animals. Adult Wistar male rats were divided into groups according to their prenatal treatment (C - naïve control; Sa - saline; MA - MA administration). One half of the animals was treated with a challenge dose of MA (1mg/kg sc.) 45min before hippocampal slices were cut. The activity of 350μ thick transversal slices of CA1 hippocampi was recorded (latencies of the first epileptiform discharge and the regular epileptiform activity) and evaluated in ACSF with low-magnesium concentration. Effects of prenatal exposure: The highest excitability was found in the Sa (prenatally stressed) group in respect to C and MA groups. This group developed also the highest number of seizure-like events. In addition, the prenatally MA treated group had also higher excitability than C group. Effects of the MA challenge dose: The challenge dose decreased the excitability of prenatally SA- exposed group. To conclude, even a mild prenatal stress significantly increases hippocampal excitability in adulthood and a challenge dose of MA is able to dampen it.
- MeSH
- epilepsie etiologie patofyziologie MeSH
- hipokampus účinky léků růst a vývoj patofyziologie MeSH
- methamfetamin toxicita MeSH
- modely nemocí na zvířatech MeSH
- náhodné rozdělení MeSH
- nedostatek hořčíku MeSH
- potkani Wistar MeSH
- psychický stres * patofyziologie MeSH
- techniky tkáňových kultur MeSH
- těhotenství MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zpožděný efekt prenatální expozice * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
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 present study has examined the anticonvulsant and neuroprotective effect of 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), a selective agonist for group II metabotropic glutamate receptors (mGluRs) when given 10-15 min after the onset of seizures induced in 12-day-old rats by bilateral icv infusion of DL-homocysteic acid (DL-HCA, 600 nmol/side). For biochemical analyses, rat pups were sacrificed during generalized clonic-tonic seizures, approximately 45-50 min after infusion of DL-HCA. Comparable time intervals were used for sacrificing the animals which received 2R,4R-APDC (0.05 nmol/side) or saline. The severity of seizures was influenced only slightly when the agonist was given after the onset of seizures, as evaluated both from the behavioral symptoms and from EEG recordings. A tendency to lower number and a shorter duration of seizures was outlined in animals posttreated with 2R,4R-APDC, but the differences did not reach the level of statistical significance. Cortical energy metabolite changes which normally accompany seizures in immature rats (large decrease of glucose and glycogen and a marked rise of lactate) were ameliorated only partially. The neuroprotective effect of 2R,4R-APDC was evaluated after 24 h and 6 days of survival following DL-HCA-induced seizures. Massive neuronal degeneration in many brain regions, mainly in the hippocampus and thalamus, following infusion of DL-HCA alone was only partially attenuated after 2R,4R-APDC posttreatment. The present findings clearly indicate that both anticonvulsant and neuroprotective effect of 2R,4R-APDC against DL-HCA-induced seizures is substantially diminished when the agonist is given after the onset of seizures as compared with its efficacy after the pretreatment (Exp. Neurol.192, 420-436, 2005).
- MeSH
- agonisté excitačních aminokyselin terapeutické užití MeSH
- cytoprotekce fyziologie účinky léků MeSH
- degenerace nervu chemicky indukované patofyziologie prevence a kontrola MeSH
- epilepsie farmakoterapie metabolismus patofyziologie MeSH
- hipokampus metabolismus růst a vývoj účinky léků MeSH
- homocystein analogy a deriváty farmakologie MeSH
- konvulziva farmakologie MeSH
- krysa rodu rattus MeSH
- lékové interakce fyziologie MeSH
- mozek metabolismus růst a vývoj účinky léků MeSH
- neuroprotektivní látky terapeutické užití MeSH
- potkani Wistar MeSH
- prolin analogy a deriváty terapeutické užití MeSH
- receptory metabotropního glutamátu agonisté metabolismus MeSH
- rozvrh dávkování léků MeSH
- stárnutí metabolismus MeSH
- thalamus metabolismus růst a vývoj účinky léků MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
V dospělém savčím mozku se nacházejí dvě primární zóny neurogeneze: gyrus dentatus a subventrikulární zóna. Nově vznikající buňky se dají identifikovat pomocí imunohistochemie označením mitotického markeru Ki-67 nebo za pomoci bromdeoxiuridinu (BrdU). BrdU je tymidový analog, který se váže na DNA v průběhu dělení buňky. V naší pilotní studii jsme sledovali účinek týdenní aplikace MDMA a citalopramu na přežívání nově vzniklých neuronů v gyrus dentatus u potkana. Semikvantifikace BrdU pozitivních buněk v gyrus dentatus ukazuje, že týdenní aplikace MDMA (5 mg/kg, 2× denně) snižuje počet BrdU pozitivních buněk ve srovnání s kontrolou. Aplikace citalo - pramu (30 mg/kg) nemá žádný vliv na přežívání nových buněk v hipokampu potkana. Doposud není známo, proč MDMA, která působí stejně jako citalopram na serotoninový transportér, snižuje neurogenezi.
Two primary zone of neurogenesis were identified in the adult mammal brain. These zones are localized in the dentate gyrus and the subventricular zone. New generated cells can be imunohistochemically stained against the mitotic marker Ki-67 or by bromdeoxyridine (BrdU). BrdU is a tymide analog, which is incorporated into the DNA during cell division. In our pilot study, we monitor the effect of MDMA and citalopram on survival of newly generated neurons in the dentate gyrus of rats. Semi-quantification of BrdU positive cells in the dentate gyrus determined that the application of MDMA (5 mg/kg, 2× day) decreased the number of BrdU-positive cells compared to the control group. The application of citalopram (30 mg/kg, 2× day) did not influence the survival of new cells in rat hippocampus. It si not yet clear why MDMA, which similar to citalopram inhibits transporter for serotonin, decreases the neurogenesis.
- MeSH
- bromodeoxyuridin diagnostické užití MeSH
- citalopram aplikace a dávkování škodlivé účinky MeSH
- financování organizované MeSH
- gyrus dentatus růst a vývoj účinky léků MeSH
- hipokampus růst a vývoj účinky léků MeSH
- imunohistochemie metody využití MeSH
- N-methyl-3,4-methylendioxyamfetamin aplikace a dávkování škodlivé účinky MeSH
- neurony účinky léků MeSH
- pilotní projekty MeSH
- potkani Wistar MeSH
N-acetyl-L-aspartyl-L-glutamate (NAAG) is a dipeptide that could be considered a sequestered form of L-glutamate. As much as 25% of L-glutamate in brain may be present in the form of NAAG. NAAG is also one of the most abundant neuroactive small molecules in the CNS: it is an agonist at Group II metabotropic glutamate receptors (mGluR II) and, at higher concentrations, at the N-methyl-D-aspartate (NMDA) type of ionotropic glutamate receptors. As such, NAAG can be either neuroprotective or neurotoxic and, in fact, both characteristics have been discussed and described in the literature. In the present studies, 250 nmol NAAG was infused into each lateral cerebral ventricle of 12-day-old rat pups and, using Nissl-stained sections, neurodegeneration in the hippocampus was evaluated 24 or 96 h after the infusion. In several experiments, the neuronal death was also visualised by Fluoro-Jade B staining and studied by TUNEL technique. Some of the NAAG-treated animals were allowed to survive until 50 days post partum and subjected to behavioural (open field) tests. The administration of NAAG to 12-day-old rats resulted in extensive death of neurons particularly in the dentate gyrus of the hippocampus. The neurodegeneration was, in part, prevented by administration of an NMDA receptor antagonist MK-801 (0.1 mg/kg). The nuclear DNA-fragmentation demonstrated by TUNEL technique pointed to the presence of non-specific single-strand DNA cleavage. The NAAG-associated neonatal neuronal damage may have perturbed development of synaptic circuitry during adolescence as indicated by an altered performance of the experimental animals in the open field testing (changes in grooming activity) at postnatal day 50. The results underscore the potential neurotoxicity of NAAG in neonatal rat brain and implicate neonatally induced, NMDA receptor-mediated neuronal loss in the development of abnormal behaviour in young adult rats.
- MeSH
- chování zvířat účinky léků MeSH
- dipeptidy aplikace a dávkování fyziologie MeSH
- financování organizované MeSH
- fragmentace DNA MeSH
- hipokampus patologie růst a vývoj účinky léků MeSH
- injekce intraventrikulární MeSH
- koncové značení zlomů DNA in situ MeSH
- krysa rodu rattus MeSH
- neurodegenerativní nemoci chemicky indukované patofyziologie patologie MeSH
- neurony patologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- MeSH
- hipokampus růst a vývoj MeSH
- lidé MeSH
- mladiství MeSH
- mozek růst a vývoj MeSH
- pití alkoholu škodlivé účinky MeSH
- poruchy paměti etiologie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- Publikační typ
- přehledy MeSH
Development of cell elements of CA1, their interaction in the process of cell differentiation during hippocampal band formation, developed CA1, and changes in the ageing process are discussed.
- MeSH
- hipokampus cytologie růst a vývoj MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- stárnutí patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
