Selective Depletion of CREB in Serotonergic Neurons Affects the Upregulation of Brain-Derived Neurotrophic Factor Evoked by Chronic Fluoxetine Treatment

Neurotrophic factors are regarded as crucial regulatory components in neuronal plasticity and are postulated to play an important role in depression pathology. The abundant expression of brain-derived neurotrophic factor (BDNF) in various brain structures seems to be of particular interest in this context, as downregulation of BDNF is postulated to be correlated with depression and its upregulation is often observed after chronic treatment with common antidepressants. It is well-known that BDNF expression is regulated by cyclic AMP response element-binding protein (CREB). In our previous study using mice lacking CREB in serotonergic neurons (Creb1TPH2CreERT2 mice), we showed that selective CREB ablation in these particular neuronal populations is crucial for drug-resistant phenotypes in the tail suspension test observed after fluoxetine administration in Creb1TPH2CreERT2 mice. The aim of this study was to investigate the molecular changes in the expression of neurotrophins in Creb1TPH2CreERT2 mice after chronic fluoxetine treatment, restricted to the brain structures implicated in depression pathology with profound serotonergic innervation including the prefrontal cortex (PFC) and hippocampus. Here, we show for the first time that BDNF upregulation observed after fluoxetine in the hippocampus or PFC might be dependent on the transcription factor CREB residing, not within these particular structures targeted by serotonergic projections, but exclusively in serotonergic neurons. This observation may shed new light on the neurotrophic hypothesis of depression, where the effects of BDNF observed after antidepressants in the hippocampus and other brain structures were rather thought to be regulated by CREB residing within the same brain structures. Overall, these results provide further evidence for the pivotal role of CREB in serotonergic neurons in maintaining mechanisms of antidepressant drug action by regulation of BDNF levels

Medycyna i Społeczeństwo. Materiały konferencyjne

Ze wstępu: "Z inicjatywy i pod patronatem Krakowskiej Szkoły Wyższej im. Andrzeja Frycza Modrzewskiego w Krakowie odbyła się w styczniu 2003 r. konferencja naukowa lekarzy, farmaceutów, biochemików, filozofów, fizjopatologów, farmakologów i klinicystów, których rozważania skupiały się wokół obszernego tematu „MED YCYNAISPOŁECZEŃSTWO Spotkanie otworzył JM Rektor Prof. KSW dr hab. Zbigniew Maciąg. Rektor wyraził podziękowanie wykładowcom i wyraził głęboką nadzieję, że kolejny numer wydawnictwa Szkoły Acta Academiae Modrevianae, złożony z wybranych prac prezentowanych na konferencji, służył będzie społeczeństwu."(...

Preživljavanje bakterije Escherichia coli O157:H7 u mlijeku izloženom visokim temperaturama i tlaku

The objective of the present study was to determine the survival of two enterohemorrhagic Escherichia coli O157:H7 strains (no. 94 and 402) and a saprophytic E. coli 1 strain at temperatures of 55 and 60 °C, and under the pressure of 300 to 600 MPa at ambient temperature (about 20 °C). The strains, in populations of 106–107 CFU/mL, were introduced into the skim milk and broth. The survival of test strains at high temperatures and high pressure depended to a high degree (p<0.05) on the type of medium in which the cells were suspended. At 55 °C the inactivation of E. coli cells was recorded after 60 to 120 min in the broth, and after 180 min in the milk. At 60 °C the time required for their thermal death was 15 to 30 min in broth. In milk only E. coli 1 cells died after 30-minute heating; the other strains survived in populations of about 40 CFU/mL. In the broth, a pressure of 550 MPa, applied for 20 min at ambient temperature, killed the entire populations of E. coli 94 and E. coli 402, and all E. coli 1 cells died at 600 MPa, also applied for 20 min at ambient temperature. In the milk live cells of all pressurized strains survived in the quantities of 102–103 CFU/mL, so their reduction by 5 log cycles was not achieved. Damaged cells were found in the majority of samples exposed to heating and high pressure. These cells did not form colonies on nutrient agar, but were able to repair damage and grow in nutrient broth at 37 °C.Ispitano je preživljavanje dvaju enterohemoragijskih sojeva bakterije Escherichia coli O157:H7 (broj 94 i 402) i saprofitnoga soja Escherichia coli 1 pri temperaturi od 55 i 60 °C, te pod tlakom od 300 do 600 MPa pri približno 20 °C. Obrano mlijeko i mesni bujon inokulirani su pojedinim sojem E. coli kako bi se postigla početna populacija od 106 do 107 CFU/mL. Preživljavanje sojeva pri visokim temperaturama i tlaku ovisilo je uvelike (p<0,05) o vrsti medija u kojem su stanice suspendirane. Pri 55 °C opažena je inaktivacija stanica E. coli u bujonu nakon 60–120 min, a u mlijeku nakon 180 min. Pri 60 °C vrijeme potrebno za toplinsko uništenje u bujonu iznosilo je 15–30 min. U mlijeku su nakon 30 min uništene samo stanice soja E. coli 1, dok su ostali sojevi preživjeli u populaciji od približno 40 CFU/mL. U bujonu je izlaganjem tlaku od 550 MPa tijekom 20 min pri 20 °C uništena cijela populacija E. coli 94 i E. coli 402, dok su pri istoj temperaturi sve stanice E. coli 1 uginule pri 600 MPa tijekom 20 min. U mlijeku je količina od 102 do 103 CFU/mL živih stanica svih sojeva preživjela pri tlaku od 550 do 600 MPa, pa se nije postiglo njihovo smanjivanje za 5 logaritamskih ciklusa. U večini uzoraka izloženih povišenoj temperaturi i tlaku nađene su oštečene stanice. One nisu mogle stvarati kolonije na hranjivom agaru, ali su bile sposobne popraviti oštećenja i rasti u hranjivom bujonu na 37 °C

Survival of Escherichia coli O157:H7 in Milk Exposed to High Temperatures and High Pressure**

The objective of the present study was to determine the survival of two enterohemorrhagic Escherichia coli O157:H7 strains (no. 94 and 402) and a saprophytic E. coli 1 strain at temperatures of 55 and 60 °C, and under the pressure of 300 to 600 MPa at ambient temperature (about 20 °C). The strains, in populations of 106–107 CFU/mL, were introduced into the skim milk and broth. The survival of test strains at high temperatures and high pressure depended to a high degree (p<0.05) on the type of medium in which the cells were suspended. At 55 °C the inactivation of E. coli cells was recorded after 60 to 120 min in the broth, and after 180 min in the milk. At 60 °C the time required for their thermal death was 15 to 30 min in broth. In milk only E. coli 1 cells died after 30-minute heating; the other strains survived in populations of about 40 CFU/mL. In the broth, a pressure of 550 MPa, applied for 20 min at ambient temperature, killed the entire populations of E. coli 94 and E. coli 402, and all E. coli 1 cells died at 600 MPa, also applied for 20 min at ambient temperature. In the milk live cells of all pressurized strains survived in the quantities of 102–103 CFU/mL, so their reduction by 5 log cycles was not achieved. Damaged cells were found in the majority of samples exposed to heating and high pressure. These cells did not form colonies on nutrient agar, but were able to repair damage and grow in nutrient broth at 37 °C

Metabolic response of RAW 264.7 macrophages to exposure to crude particulate matter and a reduced content of organic matter

Exposure to air pollution from various airborne particulate matter (PM) is regarded as a potential health risk. Airborne PM penetrates the lungs, where it is taken up by macrophages, what results in macrophage activation and can potentially lead to negative consequences for the organism. In the present study, we assessed the effects of direct exposure of RAW 264.7 macrophages to crude PM (NIST1648a) and to a reduced content of organic matter (LAp120) for up to 72 h on selected parameters of metabolic activity. These included cell viability and apoptosis, metabolic activity and cell number, ROS synthesis, nitric oxide (NO) release, and oxidative burst. The results indicated that both NIST1648a and LAp120 negatively influenced the parameters of cell viability and metabolic activity due to increased ROS synthesis. The negative effect of PM was concentration-dependent; i.e., it was the most pronounced for the highest concentration applied. The impact of PM also depended on the time of exposure, so at respective time points, PM induced different effects. There were also differences in the impact of NIST1648a and LAp120 on almost all parameters tested. The negative effect of LAp120 was more pronounced, what appeared to be associated with an increased content of metals

Polish Academy of Sciences Review

�1-Adrenergic receptor subtypes in the central nervous system: insights from genetically engineered mouse model