Multiple lines of evidence suggest the participation of the hippocampus in the feedback inhibition of the hypothalamus- pituitary-adrenal axis during stress response. This inhibition is mediated by glucocorticoid feedback due to the sensitivity of the hippocampus to these hormones. The sensitivity is determined by the expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors and 11 β -hydroxysteroid dehydrogenase type 1 (11HSD1), an enzyme that re gulates the conversion of glucocorticoids from inactive to active form. The goal of our study was to assess the effect of stress on the expression of 11HSD1, GR and MR in the ventral and dorsal region of the CA1 hippocampus in three different rat strains with diverse responses to stress: Fisher 344, Lewis and Wistar. Stress stimulated 11HSD1 in the ventral but not dorsal CA1 hippocampus of Fisher 344 but not Lewis or Wistar rats. In contrast, GR expression following stress was decreased in the dorsal but not ventral CA1 hippocampus of all three strains. MR expression was not changed in either the dorsal or ventral CA1 region. These results indicate that (1) depending on the strain, stress stimulates 11HSD1 in the ventral hippocampus, which is known to be involved in stress and emotion reactions whereas (2) independent of strain, stress inhibits GR in the dorsal hippocampus, which is predominantly involved in cognitive functions., P. Ergang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The hyperpolarization-activated cyclic-nucleotide-gated
non-selective cation (HCN) channels play a potential role in the
neurological basis underlying drug addiction. However, little is
known about the role of HCN channels in methamphetamine
(METH) abuse. In the present study, we examined the changes
in working memory functions of METH re-exposed mice through
Morris water maze test, and investigated the protein expression
of HCN1 channels and potential mechanisms underlying the
modulation of HCN channels by Western blotting analysis. Mice
were injected with METH (1 mg/kg, i.p.) once per day for
6 consecutive days. After 5 days without METH, mice were
re-exposed to METH at the same concentration. We found that
METH re-exposure caused an enhancement of working memory,
and a decrease in the HCN1 channels protein expression in both
hippocampus and prefrontal cortex. The phosphorylated
extracellular regulated protein kinase 1/2 (p-ERK1/2),
an important regulator of HCN channels, was also obviously
reduced in hippocampus and prefrontal cortex of mice with METH
re-exposure. Meanwhile, acute METH exposure did not affect the
working memory function and the protein expressions of HCN1
channels and p-ERK1/2. Overall, our data firstly showed the
aberrant protein expression of HCN1 channels in METH
re-exposed mice with enhanced working memory, which was
probably related to the down-regulation of p-ERK1/2 protein
expression.
Hypoxia is one of the major pathological factors affecting brain function. The aim of the present study was to describe the effect of neonatal hypobaric hypoxia on the behavior of rats and to analyze its effect on hippocampal neurodegeneration. Hypobaric hypoxia at a simulated altitude of 9000 m was induced for one hour in neonatal rat pups (PND7 and PND9) of both sexes. Subsequently, the rats underwent behavioral testing on PND25 and PND35 using a LABORAS apparatus to assess spontaneous behavior. Hypoxia did not cause any morphological damage in the hippocampus of rats. However, hypoxia on PND7 led to less horizontal locomotor activity both in males (on PND25) and females (on PND35). Hypoxia on PND9 led to higher rearing in females on PND25. Hypoxic males exhibited higher grooming activity, while females lower grooming activity on PND35 following hypoxia induced on PND7. In females, hypoxia on PND9 resulted in higher grooming activity on PND25. Sex differences in the effect of hypoxia were observed on PND35, when hypoxic males compared to hypoxic females displayed more locomotor, rearing and grooming activity. Our data suggest that hypoxia on PND7 versus PND9 differently affects locomotion and grooming later in adolescence and these effects are sex-dependent.
Enzymes that hydrolyze extracellular ATP, i.e. ecto-ATPase and ecto-ATP diphosphohydrolase (ATPDase), can be differentiated by ability of the latter to hydrolyze ADP and by slightly different kinetic properties of the two enzymes. Synaptic plasma membrane fractions isolated from rat hippocampus and caudate nucleus exhibit ADP-hydrolyzing activity, as revealed by the enzyme assay, and the presence of ecto-ATPase protein, as revealed by immunological identification on Western blot. These findings indicate that both enzymes are co-expressed in the synaptic membrane compartment of hippocampal and caudate nucleus neurons. Kinetic analysis was performed to determine the relative contribution of each enzyme to the total ATP-hydrolyzing activity, while an inhibition study was carried out in order to exclude the interference of other nonspecific ATPase and phosphatase activities. Based on the kinetic properties, sensitivity to inhibitors and VATP/VADP ratio of about 2, we concluded that a substantial portion of ATP-hydrolyzing activity in both synaptic membrane preparations can be ascribed to the catalytic action of ATPDase. On the other hand, the highest catalytic efficacy when ATP is the substrate and the greater abundance of ecto-ATPase protein in caudate nucleus preparation suggest that the relative contribution of ecto-ATPase to the total ATP-hydrolyzing activity in the caudate nucleus is higher than in the hippocampus., N. Nedeljkovic, A. Banjac, A. Horvat, M. Stojiljkovic, G. Nikezic., and Obsahuje bibliografii
Endothelin-1 (ET-1) is a neuroactive protein produced in most brain cell types and participates in regulation of cerebral blood flow and blood pressure. In addition to its vascular effects, ET-1 affects synaptic and nonsynaptic neuronal and glial functions. Direct application of ET-1 to the hippocampus of immature rats results in cerebral ischemia, acute seizures, and epileptogenesis. Here, we investigated whether ET-1 itself modifies the excitability of hippocampal and cortical circuitry and whether acute seizures observed in vivo are due to nonvascular actions of ET-1. We used acute hippocampal and cortical slices that were preincubated with ET-1 (20 µM) for electrophysiological recordings. None of the slices preincubated with ET-1 exhibited spontaneous epileptic activity. The slope of the stimulus intensity-evoked response (input-output) curve and shape of the evoked response did not differ between ET-1-pretreated and control groups, suggesting no changes in excitability after ET-1 treatment. The threshold for eliciting an evoked response was not significantly increased in either hippocampal or cortical regions when pretreated with ET-1. Our data suggest that acute seizures after intrahippocampal application of ET-1 in rats are likely caused by ischemia rather than by a direct action of ET-1 on brain tissue., R. Konopková ... [et al.]., and Obsahuje seznam literatury
Activation of GABAB receptors leads to longer inhibitory postsynaptic potentials than activation of GABAA receptors. Therefore GABAB receptors may be a target for anticonvulsant therapy. The present study examined possible effects of GABAB receptor agonist SKF97541 on cortical and hippocampal epileptic afterdischarges (ADs). Epileptic ADs elicited by electrical stimulation of sensorimotor cortex or dorsal hippocampus were studied in adult male Wistar rats. Stimulation series were applied 6 times with 10- or 20-min interval. Either interval was efficient for reliable elicitation of cortical ADs but stimulation at 10-min intervals did not reliably elicit hippocampal ADs, many stimulations were without effect. SKF97541 in dose 1 mg/kg significantly prolonged cortical ADs. Duration of hippocampal ADs was not significantly changed by either dose of SKF97541 in spite of a marked myorelaxant effect of the higher dose. Our present data demonstrated that neither cortical nor hippocampal ADs in adult rats were suppressed by GABAB receptor agonist SKF97541. Proconvulsant effect on cortical ADs indicates a different role in these two brain structures. In addition, duration of refractory period for electrically-induced ADs in these two structures in adult rats is different., P. Fábera, P. Mares., and Obsahuje bibliografii
Hippocampus is a brain structure containing vasopressin (AVP) fibers and specific binding sites for this peptide. There is growing evidence that AVP and its metabolites participate in glutamate-mediated plasticity of the hippocampus. The aim of the present study was to evaluate the influence of NMDA on AVP release in the rabbit hippocampus. Caudate nucleus was chosen as the reference structure. The mentioned brain structures were simultaneously microdialyzed with 0.9 % NaCl solution. AVP was determined in the outflowing fluid by radioimmunoassay. The mean basal AVP content in the fluid outflowing from the hippocampus was significantly greater than that from the caudate nucleus. The addition of K+ into the fluid perfusing the probes implanted into the hippocampus and caudate nucleus significantly increased AVP release into the extracellular fluid of both brain structures. NMDA applied into the mentioned brain structures increased AVP release only from the hippocampus but not from the caudate nucleus. Our findings indicate a role which NMDA receptors play in AVP release into the extracellular fluid of the hippocampus., M. Orłowska-Majdak, W. Z. Traczyk, D. Szymański., and Obsahuje bibliografii
Epileptic afterdischarges elicited by electrical stimulation of the dorsal hippocampus in freely moving rats were not significantly changed by flunarizine administration in comparison with control sessions in which the animals received the solvent only. On the other hand, flunarizine significantly reduced the number of wet dog shakes, the main automatisms accompanying limbic afterdischarges.
Application of knowledge about ischemic tolerance to clinic requires the solid understanding of mechanism of creation of this phenomenon. This review summarizes research that has been carried out in many laboratories over a long period of time, but the main focus will be on own experimental research. The main emphasis is devoted to the possibility of preparing full tolerance in the donor's body and its transfer to the patient in the form of activated blood plasma. Such plasma could be administered as soon as the patient is transported to the hospital and would take effect immediately after administration to the patient's bloodstream. One chapter is also devoted to anticonditioning, i.e. the possibility of preventing the activation of tolerance. Anticonditioning could be used to treat oncologic patients. We expect that this method could increase effectiveness of cancer treatment. Cross-tolerance with a wide range of diverse stressors gives us the courage to assume that activated plasma can significantly help with a wide range of pathological events., Jozef Burda, Rastislav Burda., and Obsahuje bibliografii
Domoic acid (DA) is a potent marine neurotoxine present in seafood. Intoxication by DA causes gastrointestinal symptoms like vomiting and diarrhoea and also the so-called amnesic shellfish poisoning (inflicting memory impairment and seizures). Since exposure to non-convulsive doses is relevant to the human health, we investigated the effect of low dose DA administration in adult Wistar rats. Rats were administered with DA at the dose 1.0 mg/kg and their behavior was monitored for one hour in three sessions. The first session started immediately after DA administration. The second and third session started one and two weeks later. After the third session, the histochemical analysis of the hippocampi of the animals was conducted (Fluoro-Jade B, bis-benzimide). DA increased time spent by locomotion and distance travelled in the second half of the first session and this effect was pronounced during the second and third session. Exploratory rearing was decreased by DA administration in the first half of the first session. DA influenced the grooming in biphasic manner (decrease followed by an increase of time spent by grooming). This biphasic trend was observed even two weeks after the DA administration. Histochemistry of DA treated rats did not confirm the presence of apoptotic bodies, Fluoro-Jade B positive cells were not found neither in CA1 nor CA3 area of the hippocampi. Our study revealed that a low dose of DA affect short and long-term the spontaneous behavior of rats without inducing neuronal damage., M. Schwarz, K. Jandová, I. Struk, D. Marešová, J. Pokorný, V. Riljak., and Obsahuje bibliografii