Baclofen is the only clinically available metabotropic GABA(B) receptor agonist. In our experiment, we tested the hypothesis that long-term baclofen administration can impair learning and memory in rats. The experiment consisted of three parts. In the first part of the study the drug was administered simultaneously with the beginning of the behavioral tests. In the second and third part of the experiment baclofen was administered daily for 14 days and for one month before the tests. In each part of the experiment, adult rats were randomly divided into four treatment groups. Three groups were given an injection of baclofen at doses of 1 mg/kg, 5 mg/kg, 10 mg/kg, while the fourth group was injected with saline. The injections were given after each session. Spatial learning and memory were tested using the Morris water maze, involving three types of tests: Acquisition, Probe, and Re-acquisition. This work reveals that baclofen did not affect spatial learning at any of the tested doses and regardless of the length of administration. Memory was observed to be affected, but only at the highest dose of baclofen and only temporarily. This conclusion is in line with previously published clinical cases.

• MeSH
• baklofen aplikace a dávkování   MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• paměť účinky léků   fyziologie   MeSH
• potkani Wistar MeSH
• prostorové učení účinky léků   fyziologie   MeSH
• receptory GABA-B - agonisté aplikace a dávkování   MeSH
• rozvrh dávkování léků MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The processes that organize different thoughts and memories, allowing the separation of currently relevant and irrelevant information, are collectively known as cognitive control. The neuronal mechanisms of these processes can be investigated by place cell ensemble recordings during behaviors and environmental manipulations that present cognitive control challenges to selectively represent one of multiple possible alternative estimates of location. We review place cell studies that investigate responses to manipulations that dissociate the environment into two or more spatial frames of locations, often times to test notions of pattern separation. Manipulations, such as continuously rotating the recording chamber reveal that the ensemble discharge in hippocampus self-organizes into multiple, transiently-organized representations of space, each defined by the subset of coactive cells. Ensemble discharge in the hippocampus alternates between separate representations of frame-specific positions on timescales from 25 ms to several seconds. The dynamic, functional grouping of discharge into transiently co-active subsets of cells is predicted by the animal's changing behavioral needs. In addition to identifying neural correlates of cognitive control in hippocampus, these observations demonstrate that the separation of neuronal activity into distinctive representations depends on ongoing cognitive demands and that what can appear as noise, deviations from receptive field tuning, can substantially be the result of these internal knowledge-guided fluctuations. These findings inspire a new perspective that should be taken into account when investigating pattern separation--a perspective that emphasizes changes in hippocampal neural discharge that are happening on a short timescale and does not assume that patterns of neural discharge are steady and stationary across the several minutes of the recordings.

• MeSH
• buňky místa fyziologie   MeSH
• hipokampus fyziologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• modely neurologické * MeSH
• prostorová paměť fyziologie   MeSH
• prostorové učení fyziologie   MeSH
• vnímání prostoru fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Psychostimulants, including methamphetamine (MA), have neurotoxic effect, especially, if they are targeting CNS during its critical periods of development. The present study was aimed to examine cognitive changes after prenatal and neonatal MA treatment in combination with chronic MA exposure in adulthood of male rats. Eight groups of male rats were tested in adulthood: males whose mothers were exposed to MA (5 mg/kg) or saline (SA, 1 ml/kg) during the first half of gestation period (GD 1-11), the second half of gestation period (GD 12-22) and neonatal period (PD 1-11). In addition, we compared indirect neonatal application via the breast milk with the group of rat pups that received MA or SA directly by injection (PD 1-11). Males were tested in adulthood for cognitive changes in the Morris Water Maze (MWM). MWM experiment lasted for 12 days: Learning (Day 1-6), Probe test (Day 8) and Retrieval Memory test (Day 12). Each day of the MWM animals were injected with MA (1 mg/kg) or SA (1 ml/kg). Prenatal MA exposure did not induce changes in learning abilities of male rats, but neonatal exposure to MA leads to an increase search errors and latencies to find the hidden platform. Prenatal and also neonatal MA exposure impaired cognitive ability to remember the position of the platform in Retrieval Memory test in adulthood. Animals exposed to the prenatal treatment within the second half of gestation (ED 12-22) swam longer, slower and spent more time to find the hidden platform in Retrieval Memory test than animals exposed throughout other periods. The present study demonstrated that stage of development is crucial for determination the cognitive deficits induced by prenatal or neonatal MA exposure.

• MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• methamfetamin aplikace a dávkování   toxicita   MeSH
• novorozená zvířata MeSH
• paměť účinky léků   fyziologie   MeSH
• potkani Wistar MeSH
• prostorové učení účinky léků   fyziologie   MeSH
• těhotenství MeSH
• věkové faktory MeSH
• zpožděný efekt prenatální expozice chemicky indukované   psychologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• hipokampus MeSH
• lidé MeSH
• prostorová navigace * fyziologie   MeSH
• prostorová paměť fyziologie   MeSH
• prostorové chování fyziologie   MeSH
• prostorové učení * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

There is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42 , AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD-like model mice on high-AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood-brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle-linked disease epidemic.

• MeSH
• Alzheimerova nemoc metabolismus   MeSH
• amyloidní beta-protein metabolismus   MeSH
• dieta MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• náhodné rozdělení MeSH
• produkty pokročilé glykace aplikace a dávkování   metabolismus   MeSH
• prostorové učení fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: We investigated the association between APOE ε4 status and spatial navigation in patients with amnestic mild cognitive impairment (aMCI) and assessed the role of hippocampal volume in this association. METHOD: Participants were 74 patients with clinically confirmed aMCI (33 APOE ε4 noncarriers, 26 heterozygous, and 15 homozygous ε4 carriers). Body-centered (egocentric) and world-centered (allocentric) spatial navigation in a computerized human analogue of the Morris Water Maze was assessed. Brain MRI with subsequent automated hippocampal volumetry was included. RESULTS: Groups were similar in neuropsychological profile. Controlling for age, sex, education, and free memory recall, the APOE ε4 carriers performed more poorly on all spatial navigation subtasks (ps < .05). APOE ε4 homozygotes performed worse than heterozygotes (p = .021). Right hippocampal volume accounted for the differences in allocentric and delayed subtasks (ps > .05), but not in the egocentric subtask (p < .001). CONCLUSIONS: Using an easy-to-use, computer-based tool to assess spatial navigation, we found spatial navigation deficits to worsen in a dose-dependent manner as a function of APOE ε4 status. This was at least partially due to differences in right hippocampal volume.

• MeSH
• amnézie komplikace   genetika   patologie   MeSH
• apolipoprotein E4 genetika   MeSH
• funkční lateralita MeSH
• hipokampus patologie   MeSH
• kognitivní dysfunkce komplikace   genetika   patologie   MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• počítače MeSH
• prostorová navigace fyziologie   MeSH
• prostorové učení fyziologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH