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Neurobiology
2016
In the adult mammalian brain, neurogenesis occurs in the dentate gyrus (DG) of the hippocampus throughout the life span. Neurogenesis has been extensively characterized in rodents and to a lesser extent in primates. Within the hippocampus, the adult neurogenic niche is specifically located in the subgranular zone of the DG, where neural stem/progenitor cells (NSPCs) reside. It has been confirmed that these stem cells, which possess astrocytic features, give rise to intermediate progenitors, immature neurons, and neurons. The NSPCs have radial glia-like morphology and electrolucid cytoplasm, in contrast to the immature neurons whose cytoplasm is electrodense, containing abundant polyribosome…
Glutamatergic activation of hippocampal phospholipase D: postnatal fading and receptor desensitization.
2002
Abstract: Phospholipase D (PLD) activity was determined in rat hippocampal slices between postnatal days 3 and 35. After birth, basal PLD activity was low and, within 2 weeks, increased to reach a plateau that was maintained up to the adult age. Likewise the response to glutamate developed postnatally to reach a maximum at day 8, but then faded rapidly and was almost absent at day 35. Activation of PLD by 4β-phorbol 12β,13α-dibutyrate (PDB) was independent of age, whereas the effect of aluminum fluoride (AlF4−) increased to a plateau within the first week. At day 8, PLD stimulation by glutamate via metabotropic receptors involved protein kinase C activation, but was independent of Ca2+ infl…
Age-related changes in the endocannabinoid system in the mouse hippocampus.
2015
Previous studies have demonstrated that the endocannabinoid system significantly influences the progression of brain ageing, and the hippocampus is one of the brain regions most vulnerable to ageing and neurodegeneration. We have further examined age-related changes in the hippocampal endocannabinoid system by measuring the levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in young and old mice from two different mouse strains. We found a decrease in 2-AG but not AEA levels in aged mice. In order to identify the cause for 2-AG level changes, we investigated the levels of several enzymes that contribute to synthesis and degradation of 2-AG in the hippocampus. We found a selective …
Blocking Jak/STAT signalling using tofacitinib inhibits angiogenesis in experimental arthritis
2021
Abstract Objective During rheumatoid arthritis (RA), the angiogenic processes, occurring with pannus-formation, may be a therapeutic target. JAK/STAT-pathway may play a role and the aim of this work was to investigate the inhibiting role of a JAK-inhibitor, tofacitinib, on the angiogenic mechanisms occurring during RA. Methods After ethical approval, JAK-1, JAK-3, STAT-1, STAT-3 and VEGF expression was evaluated on RA-synovial-tissues. In vitro, endothelial cells (ECs), stimulated with 20 ng/ml of VEGF and/or 1 μM of tofacitinib, were assessed for tube formation, migration and proliferation, by Matrigel, Boyden chamber assay and ki67 gene-expression. In vivo, 32 mice received collagen (coll…
Compensatory mechanisms enhance hippocampal acetylcholine release in transgenic mice expressing human acetylcholinesterase
2001
Central cholinergic neurotransmission was studied in learning-impaired transgenic mice expressing human acetylcholinesterase (hAChE-Tg). Total catalytic activity of AChE was approximately twofold higher in synaptosomes from hippocampus, striatum and cortex of hAChE-Tg mice as compared with controls (FVB/N mice). Extracellular acetylcholine (ACh) levels in the hippocampus, monitored by microdialysis in the absence or presence of 10(-8)-10(-3) M neostigmine in the perfusion fluid, were indistinguishable in freely moving control and hAChE-Tg mice. Muscarinic receptor functions were unchanged as indicated by similar effects of scopolamine on ACh release and of carbachol on inositol phosphate fo…
The Role of Monoamines in the Development of Cold-Induced Edema
1976
Our results show that even the experimentally induced high concentrations of exogenous 5-HT in the brain tissue during the early phase of edema formation are not able to increase the amount of fluid accumulation in the normal and injured brain tissue. The changes of the endogenous 5-HT levels in the blood and the brain tissue result in similar hemispheric water and RISA differences between the injured and uninjured half of the brain. Moreover, 5-HT concentrations elevated by 100% failed to produce detectable edema in the normal brain tissue of the rat.
Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus
2003
Chronic restraint stress has been shown to induce structural remodelling throughout the interconnected dentate gyrus-CA3 fields. To find out how this stressor affects the rate of adult hippocampal neurogenesis, we subjected rats to acute or chronic restraint stress and assessed the proliferation, survival and differentiation of newly born cells in the dentate gyrus. We also examined polysialylated neural cell adhesion molecule expression, a molecule normally expressed in immature neurons and important for morphological plasticity. The results show that acute restraint stress did not change either the proliferation of dentate gyrus precursor cells or the expression of polysialylated neural c…
Early histological maturation in the hippocampus of the guinea pig.
2000
The vesicular zinc-rich synaptic systems of the principal neurons of the hippocampus are well developed in newborn guinea pigs, a precocial species. In addition, alvear and fimbrial myelinated fibers as well as significant inhibitory interneurons (i.e. somatostatin, parvalbumin and opioid immunoreactive hippocampal interneurons) are also well developed. On the contrary, neither vesicular zinc synapses nor myelinated fibers nor the above mentioned immunoreactive interneurons are detectable in newborn specimens of other related altricial species such as rats or rabbits. These data suggest that early maturation of a highly integrative center related to cognitive map building such as the hippoc…
Mechanisms underlying noise-induced hearing loss
2006
Noise-induced hearing loss (NIHL) is the worldwide leading occupational disease and presents an important socio-economic factor. Despite numerous identified details about its etiology, the underlying mechanisms, which induce NIHL, have been only partially identified. In the present article, we shall discuss possible mechanisms focusing on failure in cellular calcium regulation, leading to a rise in mitochondrial NO production and reactive oxygen species formation. In cases where radical production is significantly elevated, pathological concentrations lead to alterations of cell physiological conditions and finally contribute to NIHL. A more detailed knowledge about the induction of free ra…
Hypoosmolar conditions reduce extracellular volume fraction and enhance epileptiform activity in the CA3 region of the immature rat hippocampus
2006
The osmolarity of the extracellular space (ECS) compartment is an important factor determining the excitability of neuronal tissue. In the adult hippocampus an important role of osmolarity and ECS diffusion parameters on the susceptibility to epileptic events is well established, but the influence of hypo- and hyperosmolar conditions on the immature hippocampus remains elusive. To investigate the influence of osmolarity on epileptiform activity, extracellular field potentials were recorded in the CA3 region of hippocampal slices of immature (postnatal days 4-7) Wistar rats. The ECS diffusion parameters were determined by the real-time tetramethylammonium (TMA+) iontophoretic method with ion…