Loss of Brain-Derived Neurotrophic Factor Mediates Inhibition of Hippocampal Long-Term Potentiation by High-Intensity Sound.

Exposure to noise produces cognitive and emotional disorders, and recent studies have shown that auditory stimulation or deprivation affects hippocampal function. Previously, we showed that exposure to high-intensity sound (110 dB, 1 min) strongly inhibits Schaffer-CA1 long-term potentiation (LTP). Here we investigated possible mechanisms involved in this effect. We found that exposure to 110 dB sound activates c-fos expression in hippocampal CA1 and CA3 neurons. Although sound stimulation did not affect glutamatergic or GABAergic neurotransmission in CA1, it did depress the level of brain-derived neurotrophic factor (BDNF), which is involved in promoting hippocampal synaptic plasticity. Moreover, perfusion of slices with BDNF rescued LTP in animals exposed to sound stimulation, whereas BDNF did not affect LTP in sham-stimulated rats. Furthermore, LM22A4, a TrkB receptor agonist, also rescued LTP from sound-stimulated animals. Our results indicate that depression of hippocampal BDNF mediates the inhibition of LTP produced by high-intensity sound stimulation.

Increased levels of the Akt-specific phosphatase PH domain leucine-rich repeat protein phosphatase (PHLPP)-1 in obese participants are associated with insulin resistance.

AIMS/HYPOTHESIS: We determined the contribution to insulin resistance of the PH domain leucine-rich repeat protein phosphatase (PHLPP), which dephosphorylates Akt at Ser473, inhibiting its activity. We measured the abundance of PHLPP in fat and skeletal muscle from obese participants. To study the effect of PHLPP on insulin signalling, PHLPP (also known as PHLPP1) was overexpressed in HepG2 and L6 cells. METHODS: Subcutaneous fat samples were obtained from 82 morbidly obese and ten non-obese participants. Skeletal muscle samples were obtained from 12 obese and eight non-obese participants. Quantification of PHLPP-1 in human tissues was performed by immunoblotting. The functional consequences of recombinant PHLPP1 overexpression in hepatoma HepG2 cells and L6 myoblasts were investigated. RESULTS: Of the 82 obese participants, 31 had normal fasting glucose, 33 impaired fasting glucose and 18 type 2 diabetes. PHLPP-1 abundance was twofold higher in the three obese groups than in non-obese participants (p = 0.004). No differences were observed between obese participants with normal fasting glucose, impaired fasting glucose or type 2 diabetes. PHLPP-1 abundance was correlated with basal Akt Ser473 phosphorylation (r = -0.48; p = 0.001), BMI (r = 0.44; p < 0.0001), insulin (r = 0.35; p < 0.0001) and HOMA (r = 0.38; p < 0.0001). PHLPP-1 abundance was twofold higher in the skeletal muscle of 12 obese participants than in that of eight non-obese participants (p < 0.0001). Insulin treatment of HepG2 cells resulted in a dose- and time-dependent upregulation of PHLPP-1. Overexpression of PHLPP1 in HepG2 cells and L6 myoblasts resulted in impaired insulin signalling involving Akt/glycogen synthase kinase 3, glycogen synthesis and glucose transport. CONCLUSIONS/INTERPRETATION: Increased abundance of PHLPP-1, production of which is regulated by insulin, may represent a new molecular defect in insulin-resistant states such as obesity.

Estimativas de parâmetros genéticos do perímetro escrotal e do peso corporal em animais da raça Nelore / Genetic parameters for testes size and growth in Nellore bulls

Equaçöes pelos modelos mistos adotando modelo animal foram utilizadas para estimar a herdabilidade do perímetro escrotal (PE) e do peso corporal aos 12 e 18 meses de idade e as correlaçöes genéticas entre estas características em animais da raça Nelore. Foram coletados trimestralmente os PE e os pesos de 871 bezerros da raça Nelore, filhos de 45 reprodutores e nascidos nos meses de setembro a dezembro, nos anos de 1991 e 1992. Os pesos aos 12 e aos 18 meses de idade foram obtidos por interpolaçöes e os PE nestas mesmas idades foram tomados, respectivamente, entre 275 e 455 dias de idade e entre 456 e 635 dias de idade. Pesos e PE médios mais ou menos desvios padräo foram 249 mais ou menos 31 kg, 363 mais ou menos 41 kg, 22 mais ou menos 3 cm e 27 mais ou menos 3 cm, respectivamente, aos 12 e 18 meses de idade. Na mesma sequência, estimativas de herdabilidade mais ou menos erros padräo foram 0,32 mais ou menos 0,05, 0,42 mais ou menos 0,06, 0,47 mais ou menos 0,07 e 0,74 mais ou menos 0,06. Correlaçöes genéticas entre PE e pesos foram altas (de 0,46 até 0,52), assim como foram altas as correlaçöes genéticas entre os dois pesos (0,68) e entre os dois PE (0,76). Resultados sugerem que a seleçäo para PE seria mais efetiva quando praticada aos 18 meses de idade, tanto em termos de resposta direta à seleçäo como em termos de resposta correlacionada no peso corporal