Biomedical subjects

Ana Olariu

Publications and source records attributed to Ana Olariu.

7 recordsLinked to original sources

PubMed2006

Novel role for aspartoacylase in regulation of BDNF and timing of postnatal oligodendrogenesis.

Neuronal growth factors are thought to exert a significant degree of control over postnatal oligodendrogenesis, but mechanisms by which these factors coordinateoligodendrocyte development with the maturation of neural networks are poorly characterized. We present here a developmental analysis of aspartoacylase (Aspa)-null tremor rats and show a potential role for this hydrolytic enzyme in the regulation of a postnatal neurotrophic stimulus that impacts on early stages of oligodendrocyte differentiation. Abnormally high levels of brain-derived neurotrophic factor (BDNF) expression in the Aspa-null Tremor brain are associated with dysregulated oligodendrogenesis at a stage in development normally characterized by high levels of Aspa expression. BDNF promotes the survival of proliferating cells during the early stages of oligodendrocyte maturation in vitro, but seems to compromise the ability of these cells to populate the cortex in vivo. Aspartoacylase activity in oligodendrocytes is shown to provide for the negative regulation of BDNF in neurons, thereby determining the availability of a developmental stimulus via a mechanism that links oligodendroglial differentiation with neuronal maturation.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed2005

Amyloid pathology and protein kinase C (PKC): possible therapeutics effects of PKC activators.

Amyloid beta-protein (Abeta) is one of the most studied peptides in human neurodegenerative disorders. Although much has been learned about the biochemistry of this peptide, fundamental questions such as when and how the Abeta becomes pathologic remain unanswered. In this article we review the recent findings on the biology and pathology of Abeta and the role protein kinase C (PKC) plays in these processes. The potential neuroprotective role of PKC and the possible therapeutic effects of PKC activators in Alzheimer's disease (AD) will be discussed. Briefly, comments will be also addressed on the role of PKC in cell death and neurogenesis in AD.

Amyloid↗

PubMed2005

A natural form of learning can increase and decrease the survival of new neurons in the dentate gyrus.

Granule cells born in the adult dentate gyrus undergo a 4-week developmental period characterized by high susceptibility to cell death. Two forms of hippocampus-dependent learning have been shown to rescue many of the new neurons during this critical period. Here, we show that a natural form of associative learning, social transmission of food preference (STFP), can either increase or decrease the survival of young granule cells in adult rats. Increased numbers of pyknotic as well as phospho-Akt-expressing BrdU-labeled cells were seen 1 day after STFP training, indicating that training rapidly induces both cell death and active suppression of cell death in different subsets. A single day of training for STFP increased the survival of 8-day-old BrdU-labeled cells when examined 1 week later. In contrast, 2 days of training decreased the survival of BrdU-labeled cells and the density of immature neurons, identified with crmp-4. This change from increased to decreased survival could not be accounted for by the ages of the cells. Instead, we propose that training may initially increase young granule cell survival, then, if continued, cause them to die. This complex regulation of cell death could potentially serve to maintain granule cells that are actively involved in memory consolidation, while rapidly using and discarding young granule cells whose training is complete to make space for new naïve neurons.

Animals↗

PubMed2005

Stress in early life inhibits neurogenesis in adulthood.

Both structure and function of the hippocampus are altered by stress: by increasing levels of corticosteroids, stress causes atrophy of CA3 pyramidal cell dendrites, inhibits adult neurogenesis in the dentate gyrus, and impairs hippocampus-dependent learning. A recent study shows that adverse experience limited to early life, specifically removal of rat pups from their mother for three hours each day, decreases production of new granule neurons in adulthood through a corticosteroid-dependent mechanism. This finding suggests that stress in early life could permanently impair hippocampus-dependent learning and memory and increase susceptibility to depression by inhibiting adult neurogenesis in the hippocampus.

Adrenal Cortex Hormones↗

PubMed2004

The modulator role of the hypothalamic paraventricular nucleus on immune responsiveness.

Role of the paraventricular nucleus of the hypothalamus (PVH) upon immune modulation was studied by either mechanically destroying the PVH (PVHL) or by isolating the PVH (PVHI) with a knife-cut. PVHL or PVHI manipulations induced significant leukopenia characterized by a decrease in the number of neutrophils and lymphocytes two weeks post surgery. The numbers of circulating monocytes and eosinophils were not affected by PVH interventions. In addition, PVHL and PVHI were also associated with a reduction, relative to controls, in the phagocytosis by neutrophils and an increase in blastic transformation of T lymphocytes induced by phytohemagglutinin-M (PHA-M). Antibody titers rose against sheep red blood cells (SRBC) after either PVHL or PVHI were reduced. The magnitude of the SRBC antibody reduction after PVH manipulations was similar to that observed in rats that received a peripheral chemical sympathectomy two hrs prior immunization. Comparison of thyroid hormones blood levels two weeks after PVHL or PVHI revealed significant reductions in comparison with sham-operated group (SO), whereas blood corticosterone was not significantly altered. In summary, we provide evidence that lesion or isolation of the PVH selectively reduces circulating white blood cells and the primary immune response, while it enhances the cell-mediated immune function. Taken together our data showed that PVH modulates immune functions by altering both the peripheral sympathetic tone and thyroid hormone secretion.

Animals↗

PubMed2003

Effects of nicotine on memory impairment induced by blockade of muscarinic, nicotinic and dopamine D2 receptors in rats.

Scopolamine dose-dependently inhibits passive avoidance latency and decreases spontaneous alternation in the Y-maze, suggesting effects on long-term and short-term memory, respectively. Chlorisondamine (10 mg/kg), a compound which produces a long-lasting central nicotinic receptor blockade, did not affect short-term and long-term memory performance. In normal rats, nicotine at the doses of 0.3, 1.0, and 3.0 mg/kg administered once had a facilitating effect on short-term memory; a higher dose (3.0 mg/kg) did not show a more pronounced effect than a lower one (0.3 mg/kg). Nicotine, by activating the nicotinic acetylcholine receptors, attenuated the impairment of short-term memory induced by muscarinic or dopamine D2 receptor blockade. On long-term memory, a single dose of nicotine (0.3, 1.0, 3.0 mg/kg) did not affect memory performance, but improved it after chronic (10 consecutive days, 0.3 mg/kg) administration. The antiamnesic effect of nicotine administered once was observed in scopolamine-, scopolamine+chlorisondamine- or sulpiride-treated rats. These results suggest that the antiamnesic effect of nicotine can result from an action at nicotinic receptors subtypes not blocked by chlorisondamine or at nonnicotinic receptors.

Animals↗

PubMed2002

Memory impairment induced by chronic intracerebroventricular infusion of beta-amyloid (1-40) involves downregulation of protein kinase C.

Signaling pathways underlying the cognitive deficit of the Alzheimer's disease (AD) are not completely understood. Protein kinase C (PKC), a major neuronal protein plays a critical role in cellular signal transduction and it is known to be subjected to modulation in AD. We showed previously that, chronic infusion of beta-amyloid (1-40) into rat cerebroventricle leads to deficit in spatial and non-spatial memory formation. As an attempt to identify the cellular correlates of the memory deficit, in the present study we investigated the PKC activation in different brain areas. Chronic infusion of beta-amyloid (1-40) for 14 days into the rat cerebroventricle decreased the activity of soluble protein kinase C (PKC) in the hippocampus. Subcellular translocation of PKC to membrane fraction in hippocampal slices of rats treated with beta-amyloid (1-40) was completely abolished under acute stimulation with 0.5 microM phorbol-dibutyrate (PDBu). We also reported a decreased affinity (k(D)) for PDBu binding in the hippocampus, cerebral cortex and striatum. The total number of binding sites for PDBu (B(max)) was increased, in the three brain areas analyzed on the day 14, but the changes were not statistically significant. Our data indicate that chronic accumulation of beta-amyloid (1-40) into the rat brain reduced activation of PKC, effect that would substantially contribute to the memory deficit found in these animals.

Alzheimer Disease↗