INTRODUCTION: Morphological correlates of nonpathological déjà vu (DV) have been identified recently within the human brain. Significantly reduced gray matter volume (GMV) within a set of cortical and subcortical regions reported in subjects experiencing DV seems to mirror the distribution of GMV reduction in mesial temporal lobe epilepsy (MTLE) patients but vary in terms of the hippocampus. Another condition associated with hippocampal GMV reduction and DV alike disturbance in memory processing is schizophrenia (SCH). Here, we tested the hypothesis that hippocampal involvement in nonpathological DV resembles more closely the pattern of GMV decrease observed in MTLE compared with that occurring in SCH. METHODS: Using automated segmentation of the MRI data we compared the medians of GMV within 12 specific hippocampal subfields in healthy individuals that do (DV+; N = 87) and do not report déjà vu experience (DV-; N = 26), and patients with MTLE (N = 47) and SCH (N = 29). By Pearson correlation, we then evaluated the similarity of MTLE and SCH groups to DV+ group with respect to spatial distribution of GMV deviation from DV- group. RESULTS: Significant GMV decrease was found in MTLE group in most of the subfields. There were just trends in the hippocampal GMV decrease found in DV+ or SCH groups. Concerning the spatial distribution of GMV decrease, we revealed statistically significant correlation for the left hippocampus for SCH vs DV+. Otherwise there was no statistically significant correlation. CONCLUSIONS: Our findings reveal structural features of hippocampal involvement in nonpathological DV, MTLE, and SCH. Despite our expectations, the pattern of GMV reduction in the DV+ relative to the DV- group does not resemble the pattern observed in MTLE any more than that observed in SCH. The highly similar patterns of the three clinical groups rather suggest an increased vulnerability of certain hippocampal subfields; namely, Cornu Ammonis (CA)4, CA3, dentate gyrus granular cell layer (GC-DG), hippocampal-amygdaloid transition area (HATA) and subiculum.

• Klíčová slova
• deja vu, hippocampal subfields, hippocampal vulnerability, mesial temporal lobe epilepsy, schizophrenia,
• MeSH
• déja vu psychologie   MeSH
• dospělí MeSH
• epilepsie temporálního laloku patofyziologie   MeSH
• hipokampus fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mapování mozku MeSH
• mladiství MeSH
• mladý dospělý MeSH
• schizofrenie patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

There is an increasing evidence that corticosteroids damage the hippocampus in rodents and in primates. Hippocampal atrophy induced by corticosteroids may play an important role in the pathogenesis of a range of neuropsychiatric disorders. Hippocampus is necessary for short-term memory consolidation and HPA axis regulation. Signs of hippocampal damage (HPA dysregulation in combination with memory impairment) are found in affective disorders, Alzheimer's disease and in posttraumatic stress disorder. MRI volumetry reveals reduced hippocampal volume in these diseases. Evidence supporting the "glucocorticoid hypothesis" of psychiatric disorders is reviewed in the first part of the paper. Unresolved questions concerning temporary aspects of neurodegeneration, causality, reversibility, type of damage, factors increasing hippocampal vulnerability, and both pharmacological (CRH antagonists, antiglucocorticoid drugs, GABA-ergic, serotonergic, glutamatergic agents) and non-pharmacological (psychotherapy) treatment approaches are discussed in the second part.

• MeSH
• Alzheimerova nemoc etiologie   metabolismus   prevence a kontrola   MeSH
• antiflogistika škodlivé účinky   MeSH
• atrofie chemicky indukované   metabolismus   patologie   MeSH
• degenerace nervu patologie   MeSH
• hipokampus metabolismus   patologie   MeSH
• hydrokortison metabolismus   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antiflogistika MeSH
• hydrokortison MeSH

The interaction between the main psychotropic ingredient of Cannabis, Δ⁹- tetrahydrocannabinol (THC), with the endogenous cannabinoid system (ECS) is a critical and underrated issue that deserves utmost attention. The ECS, indeed, contributes to the formation and regulation of excitatory and inhibitory (E/I) neuronal networks that in the hippocampus underly spatial memory. This study explored sex-specific consequences of prenatal exposure to THC in hippocampus-dependent memory and the underlying cellular and molecular contributors of synaptic plasticity and E/I homeostasis. Sprague Dawley dams were exposed to THC (2 mg/kg) or vehicle, from gestational day 5-20. The adolescent progeny of both sexes was tested for: spatial memory retrieval and flexibility in the Barnes Maze; mRNA expression of relevant players of hippocampal synaptic plasticity; density of cholecystokinin-positive basket cells (CCK+BCs) - a major subtype of hippocampal inhibitory interneurons; mRNA expression of the excitatory and inhibitory synaptic proteins neuroligins (Nlgns), as a proxy of synaptic efficiency. Our results show a sex-specific disruption in spatial memory retrieval and flexibility, a male-specific decrease in CCK+BCs density and increase in the expression of markers of neuroplasticity, and consistent changes in the expression of Nlgn-1 and 3 isoforms. Despite a delay in memory retrieval, flexibility of memory was spared in prenatally-THC-exposed female offspring as well as most of the markers of neuroplasticity; a sex-specific increase in CCK+BCs density, and a consistent expression of Nlgn-3 was observed. The current results highlight a major vulnerability to prenatal exposure to THC on memory processing in the male progeny, and sex-specific alterations in the E/I balance and synaptic plasticity.

• Klíčová slova
• Excitatory/inhibitory balance, Hippocampus, Prenatal THC exposure, Sex-related vulnerability, Spatial memory,
• MeSH
• bludiště - učení účinky léků   MeSH
• cholecystokinin metabolismus   MeSH
• hipokampus * účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• neuroplasticita * účinky léků   MeSH
• pohlavní dimorfismus * MeSH
• potkani Sprague-Dawley * MeSH
• prostorová paměť * účinky léků   MeSH
• těhotenství MeSH
• tetrahydrokanabinol * farmakologie   toxicita   MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cholecystokinin MeSH
• tetrahydrokanabinol * MeSH

Neurotoxic effect of ethanol on the CNS of laboratory rats in the prenatal and postnatal period was studied. Another aim of the experiment was to analyse structure of the hippocampus after the prenatal and postnatal exposure to alcohol and to identify the most vulnerable hippocampal regions. Pregnant Wistar rats of our own breed received 20% alcohol p.o. ad libitum every day since the conception to the 18th day of postnatal life of their offspring. Since the birth (the day 1) till the age of 18 days offspring were kept together with their mother and were exposed to postnatal alcohol effect (alcohol in the breast milk). At the age of 18 days animals were perfused under deep thiopental anaesthesia with buffered solution of paraformaldehyde. Serial sections were stained with Fluoro-Jade B and DNA specific dye bis-benzimide (Hoechst No 33258). Brains of young rats aged 18 days were analysed under the light microscope Olympus Provis AX-70 with epifluorescence. In CA1 and CA3 areas and in Gyrus dentatus of the hippocampus, groups of degenerating cells were observed. In all offspring some cells with fine granulated karyons were identified, which were accompanied with high numbers of glial cells. Our results demonstrate the neurotoxic effects of alcohol and the high vulnerability of the developing CNS. The identification of cells with segmented karyons indicates the role of apoptotic mechanism in the cell death.

• MeSH
• ethanol toxicita   MeSH
• gyrus dentatus účinky léků   patologie   MeSH
• hipokampus účinky léků   patologie   MeSH
• krysa rodu Rattus MeSH
• laktace * MeSH
• plod účinky léků   MeSH
• potkani Wistar MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ethanol MeSH

The effect of ethanol on the structural development of the central nervous system was studied in offspring of Wistar rats, drinking 20 % ethanol during pregnancy and till the 28th day of their postnatal life. The structural changes in the hippocampus and dentate gyrus were analyzed at the age of 18, 35 and 90 days. A lower width of pyramidal and granular cell layers, cell extinction and fragmentation of numerous nuclei were found in all experimental animals compared to control animals. The extent of neural cell loss was similar in all monitored areas and in all age groups. At the age of 18 and 35 days, the degenerating cells were observed in the CA1 and CA3 area of the hippocampus and in the ventral and dorsal blade of the dentate gyrus. Numerous glial cells replaced the neuronal population of this region. Some degenerating cells with fragmented nuclei were observed at the age of 90 days. Our experiments confirmed the vulnerability of the developing central nervous system by ethanol intake during the perinatal period and revealed a long-lasting degeneration process in the hippocampus and dentate gyrus.

• MeSH
• analýza rozptylu MeSH
• ethanol toxicita   MeSH
• gyrus dentatus účinky léků   embryologie   růst a vývoj   patologie   MeSH
• hipokampus účinky léků   embryologie   růst a vývoj   patologie   MeSH
• krysa rodu Rattus MeSH
• látky tlumící činnost CNS toxicita   MeSH
• longitudinální studie MeSH
• neparametrická statistika MeSH
• neurony účinky léků   patologie   MeSH
• pití alkoholu patologie   MeSH
• potkani Wistar MeSH
• těhotenství MeSH
• velikost orgánu MeSH
• zpožděný efekt prenatální expozice patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ethanol MeSH
• látky tlumící činnost CNS MeSH

OBJECTIVES: Changes in the hippocampus induced by water intoxication were studied using fluorescence microscopy (FM) and magnetic resonance imaging (MRI). METHODS: In three animals (rats), intracellular/extracellular distribution of Evans blue (EB) in cerebral cortex and hippocampus of both hemispheres was revealed by injection of EB into the internal carotid artery (ICA) in hyperhydrated rats (water intoxication, WI). A total of 8 experimental rats were used for the MRI study. The animals were scanned before WI, then the experimental brain edema was induced by WI and MR scanning was performed at day 1 and day 8 after WI. Besides standard T2-weighted imaging an apparent diffusion coefficient (ADC) and transverse relaxation time (T2) were evaluated. RESULTS: Hyperhydration brought about the largest intracellular deposits of EB in CA3 hippocampal region, followed by the cerebral cortex and CA1 hippocampal region with the lowest amount of intracellular EB in the dentate gyrus. A higher apparent diffusion coefficient (corresponding to a vasogenic edema) was found the first day after hyperhydration in the cortex and in the CA1 and CA3 regions with no changes in dentate gyrus. CONCLUSION: Both FM and MRI confirmed a selectively higher vulnerability to hyperhydration and hyponatremia (achieved by water intoxication) of the hippocampal cells compared to dentate gyrus cells.

• MeSH
• edém mozku * diagnostické zobrazování   MeSH
• Evansova modř MeSH
• fluorescenční mikroskopie MeSH
• hipokampus * diagnostické zobrazování   MeSH
• intoxikace vodou MeSH
• krysa rodu Rattus MeSH
• magnetická rezonanční tomografie MeSH
• mozek MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Evansova modř MeSH

To study possible functional involvement of gamma-glutamyl transpeptidase (GGT) in glutamate transmitter metabolism we lesioned putative glutamatergic structures of the rat hippocampal formation by intracerebroventricular (i.c.v.) injection of kainic acid (KA) or by surgical CA3 axotomy. Unilateral injection of KA into the left lateral cerebral ventricle of 30-day-old rats resulted in decreased GGT activity in hippocampal areas CA3, Ca1 ipsilaterally, and in the contralateral area CA1, four hours after the induction of the chemical lesion. Four days after the injection, the enzyme activity was decreased in all hippocampal areas with the exception of the contralateral dentate gyrus. Four days after bilateral i.c.v. injection of KA, lower GGT levels were found than was seen after bilateral surgical lesion of the CA3 pyramidal cell axons (Schaffer's collaterals). The surgical lesion was followed by a decrease of GGT only in the stratum pyramidale and stratum radiatum of area CA1. In contrast to the effects in 30-day-old rats, unilateral i.c.v. injection of KA on postnatal day 12 did not alter the GGT activity in any studied hippocampal area presumably because of incomplete maturation of structures required for KA vulnerability.

• MeSH
• časové faktory MeSH
• gama-glutamyltransferasa metabolismus   MeSH
• hipokampus účinky léků   enzymologie   MeSH
• inbrední kmeny potkanů MeSH
• injekce intraventrikulární MeSH
• krysa rodu Rattus MeSH
• kyselina kainová farmakologie   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• gama-glutamyltransferasa MeSH
• kyselina kainová MeSH

It is suggested that intracellular tau protein (τ), when released extracellularly upon neuron degeneration, could evoke direct toxic effects on the cholinergic neurotransmitter system through muscarinic receptors and thus contribute to the pathogenesis of Alzheimer's disease. In this study, we evaluated the in vitro effects of six naturally occurring monomeric τ isoforms on rat hippocampal synaptosomal choline transporters CHT1 (large transmembrane proteins associated with high-affinity choline transport and vulnerable to actions of amyloid β peptides (Aβ) applied in vitro or in vivo). Some τ isoforms at nM concentrations inhibited choline transport in a dose- and time-dependent saturable manner (352 = 441 > 410 = 383 > 381 = 412) and effects were associated with changes in the Michaelis constant rather than in maximal velocity. Moreover, the actions of τ 352/441 were not influenced by previous depolarisation of synaptosomes or by previous depletion of membrane cholesterol. Specific binding of [3H]hemicholinium-3 was not significantly altered by τ 352/441 at higher nM concentrations. Results of in vitro tests on CHT1 transporters from cholesterol-depleted synaptosomes supported interactions between Aβ 1-40 and τ 352. In addition, we developed surface plasmon resonance biosensors to monitor complexes of Aβ 1-42 and τ 352 using a sandwich detection format. It seems, therefore, that protein τ, similar to Aβ peptides, can contribute to the pathogenesis of Alzheimer's disease through its actions on CHT1 transporters. However, the interaction mechanisms are quite different (τ probably exerts its effects through direct interactions of microtubule binding repeats with extracellular portions of the CHT1 protein without influencing the choline recognition site, Aβ rather through lipid rafts in the surrounding membranes). An N-terminal insert of τ is not necessary but the N-terminal projection domain plays a role. The developed biosensor will be used to detect Aβ-τ complexes in cerebrospinal fluid in order to evaluate them as prospective biomarkers of Alzheimer's disease.

• MeSH
• amyloidní beta-protein metabolismus   MeSH
• hipokampus metabolismus   MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• povrchová plasmonová rezonance MeSH
• proteiny přenášející kationty metabolismus   MeSH
• proteiny tau metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amyloidní beta-protein MeSH
• CHT1 protein, rat MeSH Prohlížeč
• proteiny přenášející kationty MeSH
• proteiny tau MeSH

Vulnerability of hippocampal hemicholinium-3 (HC-3)-sensitive carriers to ethanol was evaluated in vitro during rat postnatal development. The high-affinity uptake of [3H]choline (HACU) and the specific binding of [3H]HC-3 were measured on synaptosomes from 7-, 14-, and 60-day-and 3-month-old male and female Wistar rats. Marked increases of basal (between 7 and 60 days of age) and of stimulated HACU levels via K(+)-depolarization (between 14 days and 3 months) but only a mild elevation in [3H]HC-3 binding (between 7 days and 3 months) associated with alterations in the binding site number were found. On the mature tissue, ethanol at high concentrations (5%) moderately inhibited the choline transport under basal conditions but totally eliminated depolarization effects. However, both age- and sex-dependent alterations in basal HACU mediated by high or low pharmacologically relevant alcohol concentrations (50-100 mM) were observed in the immature tissue. Namely, the dose- and incubation time-dependent inhibition of HACU associated with changes in the transport velocity was found in postnatal male but not female tissue. [3H]HC-3 binding site was not markedly sensitive to ethanol actions. Anisotropy measurements in the region of the hydrophilic heads of phospholipid bilayers and in the membrane hydrocarbon core indicated penetration of 100 mM ethanol to immature female but not male tissue. Our results suggest the noncompetitive binding of alcohol to choline carriers from immature male tissue and correspond with data reporting significant sexual dimorphism of postnatal hippocampal neurons. The direct effects of ethanol on male choline carriers can contribute to the inhibition of acetylcholine synthesis and to sex-dependent neurotoxic effects of alcohol applied in vivo during early and late postnatal period.

• MeSH
• anizotropie MeSH
• biologický transport účinky léků   MeSH
• časové faktory MeSH
• cholin farmakokinetika   MeSH
• cholinergní látky metabolismus   MeSH
• ethanol aplikace a dávkování   farmakologie   MeSH
• hemicholinium 3 metabolismus   MeSH
• hipokampus metabolismus   MeSH
• kompetitivní vazba účinky léků   MeSH
• krysa rodu Rattus MeSH
• látky tlumící činnost CNS aplikace a dávkování   farmakologie   MeSH
• lipidové dvojvrstvy metabolismus   MeSH
• membránové transportní proteiny účinky léků   metabolismus   MeSH
• novorozená zvířata růst a vývoj   metabolismus   MeSH
• pohlavní dimorfismus * MeSH
• potkani Wistar MeSH
• stárnutí metabolismus   MeSH
• vazebná místa účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cholin MeSH
• choline transporter MeSH Prohlížeč
• cholinergní látky MeSH
• ethanol MeSH
• hemicholinium 3 MeSH
• látky tlumící činnost CNS MeSH
• lipidové dvojvrstvy MeSH
• membránové transportní proteiny MeSH

Studies suggest age- and sex-dependent structural and functional patterns of human cerebral lateralization underlie hemisphere specialization and its alterations in schizophrenia. Recent works report sexual dimorphism of neurons in the hippocampal formation and specialization of hemispheres in rats. Our experiments indicate for the first time functional lateralization of the high-affinity choline uptake (HACU) system directly associated with a synthesis of acetylcholine in the hippocampus of Wistar rats. The markedly increased HACU activity was found in the left compared to the right hippocampus of adult male but not female animals. Lineweaver-Burk plot analysis revealed a statistically significant increase of Vmax in the left hippocampus of 14-day-old when compared to 7-day-old males. It appears that laterality of HACU occurs during late postnatal maturation, and its degree is markedly enhanced after puberty and attenuated during aging. Quinolinic acid (QUIN), an endogenous agonist of N-methyl-D-aspartate type glutamate receptors, was used in this study to evaluate the neurodevelopmental hypothesis of schizophrenia. It is known that elevated levels of QUIN accompany viral infections, increasing the risk of developing schizophrenia. Bilateral intracerebroventricular application of QUIN (250 nmoles/ventricle) to pups aged 12 days significantly impaired the cholinergic hippocampal system of adolescent male and female rats and reversed lateralization of male HACU. Morphological analysis indicated marked changes in brain lesion sizes (extensive 24 h and moderate 38 days after the operation). Asymmetry of lesions was observed in the majority of cases, but the left hemisphere was not generally more vulnerable to QUIN effects than the right side. Moreover, no lateral differences were found between lesioned hippocampi in the specific binding of [3H]hemicholinium-3 (10%-15% loss of binding sites when compared to sham-operated animals). In summary, our results indicate a symmetrical drop in the number of choline carriers of lesioned male rats but a asymmetrical decrease in the activity of remaing carriers, suggesting defects in processes of sexual brain differentiation, leading under normal conditions to the higher activity of carriers in the left hippocampus. The data demonstrate viral infection-mediated alterations in normal patterns of brain asymmetry and are discussed in relation to animal models of neurodevelopmental and neurodegenerative diseases.

• MeSH
• funkční lateralita * MeSH
• hipokampus patofyziologie   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech * MeSH
• neurodegenerativní nemoci patofyziologie   MeSH
• potkani Wistar MeSH
• receptory cholinergní fyziologie   MeSH
• sexuální faktory MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptory cholinergní MeSH