Biomedical subjects

C Brandoli

Publications and source records attributed to C Brandoli.

6 recordsLinked to original sources

PubMed2001

Dexamethasone reduces the expression of p75 neurotrophin receptor and apoptosis in contused spinal cord.

Apoptosis is an important cause of secondary cell death in spinal cord injury (SCI). SCI induces the expression of the low affinity neurotrophin receptor p75 (p75NTR), that in the absence of the high affinity component, TrkA, can promote cell death by apoptosis. We therefore hypothesized that a reduction of p75NTR expression in SCI may increase tissue sparing and therefore improve recovery of function. As a tool to test our hypothesis we used the synthetic glucocorticoid dexamethasone (DEX) to down-regulate p75NTR expression. A standardized thoracic spinal cord contusion injury was produced in female rats. Laminectomized and SCI rats received various doses of DEX immediately after injury and the treatment was continued daily for 7 days. DEX, given at high doses (20 mg/kg, s.c.) but not at low doses (1 or 8 mg/kg) prevented the increase in p75NTR mRNA and protein in SCI rats, without affecting the expression of TrkA. High doses of DEX also reduced cellular apoptosis both in white and gray matters. This effect correlated with the ability of DEX to accelerate behavioral recovery of function measured by a combined behavioral score. These data suggest that reduction of p75NTR in SCI may be a therapeutic strategy to limit cell and tissue damage and therefore to improve recovery of function in SCI patients.

Animals↗

PubMed1998

Dexamethasone induces hypertrophy of developing medial septum cholinergic neurons: potential role of nerve growth factor.

Glucocorticoid hormones influence neuronal plasticity during development; however little is known about the mechanisms of this trophic activity. Because glucocorticoids increase nerve growth factor (NGF) synthesis in selected brain areas and NGF plays a role in the development of basal forebrain cholinergic neurons, we tested the hypothesis that glucocorticoids may foster maturation of the cholinergic phenotype during postnatal development via the induction of NGF biosynthesis. The synthetic glucocorticoid dexamethasone (DEX) was injected systemically (0.5 mg/kg, s.c.) once a day for 1 week in 7-d-old (P7) rats. DEX elicited an increase in NGF mRNA and protein levels in the cerebral cortex and hippocampus as well as specific NGF responses, such as TrkA tyrosine phosphorylation in the septum, choline acetyltransferase (ChAT) and p75 neurotrophin receptor (p75NTR) immunoreactivity, and a relative number of cholinergic neurons in the medial septum. To examine whether the effect of DEX is age-related, we treated 1- and 14-d-old rats with DEX for 1 week. DEX increased NGF expression in rats treated from P1 to P8 but not in those treated from P14 to P21. The age-related increased expression of NGF correlated with the induction of ChAT immunoreactivity in the medial septum. Moreover, in the spinal cord, neither NGF nor ChAT levels were increased by DEX, suggesting that the glucocorticoid-mediated changes seen in the basal forebrain are associated with specific NGF responses. Our data suggest that by increasing NGF levels, glucocorticoids may play a role in the maturation of postnatal cholinergic neurons.

Age Factors↗

PubMed1998

Brain-derived neurotrophic factor and basic fibroblast growth factor downregulate NMDA receptor function in cerebellar granule cells.

Evidence has accumulated to suggest that the NMDA glutamate receptor subtype plays an important role in neuronal degeneration evoked by hypoxia, ischemia, or trauma. Cerebellar granule cells in culture are vulnerable to NMDA-induced neuronal excitotoxicity. In these cells, brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (FGF2) prevent the excitotoxic effect of NMDA. However, little is known about the molecular mechanisms underlying the protective properties of these trophic factors. Using cultured rat cerebellar granule cells, we investigated whether BDNF and FGF2 prevent NMDA toxicity by downregulating NMDA receptor function. Western blot and RNase protection analyses were used to determine the expression of the various NMDA receptor subunits (NR1, NR2A, NR2B, and NR2C) after BDNF or FGF2 treatment. FGF2 and BDNF elicited a time-dependent decrease in the expression of NR2A and NR2C subunits. Because NMDA receptor activation leads to increased intracellular Ca2+ concentration ([Ca2+]i), we studied the effect of the BDNF- and FGF2-induced reduction in NR2A and NR2C synthesis on the NMDA-evoked Ca2+ responses by single-cell fura-2 fluorescence ratio imaging. BDNF and FGF2 reduced the NMDA-mediated [Ca2+]i increase with a time dependency that correlates with their ability to decrease NR2A and NR2C subunit expression, suggesting that these trophic factors also induce a functional downregulation of the NMDA receptor. Because sustained [Ca2+]i is believed to be causally related to neuronal injury, we suggest that BDNF and FGF2 may protect cerebellar granule cells against excitotoxicity by altering the NMDA receptor-Ca2+ signaling via a downregulation of NMDA receptor subunit expression.

Animals↗

PubMed1997

Prenatal exposure to methylmercury during late gestation affects cerebral opiatergic system in rat offspring.

Pregnant female rats were orally administered a single dose (8 mg/kg) of methylmercury chloride (MMC) on Day 15 of gestation. The binding characteristics of opioid receptors were studied in the brain of developing rats at different stages of age. An increased density of opioid receptors was found in whole brain of MMC-exposed rats at 21 days (delta receptors) and 60 days (mu and delta receptors) of age, in comparison with matched controls. An enhanced response to morphine administration was detected in MMC-exposed rat offspring at Day 60 of postnatal life, which, however, was not apparently due to an impaired liver metabolization or renal excretion. Hence, it is reasonable to surmise a possible correlation between receptor up-regulation and increased response to pharmacological challenge. These data seem to indicate that neurochemical alterations produced in the rat developing organism by prenatal exposure to methylmercury involve the opiatergic system which undergoes a supersensitivity phenomenon. This effect, which is not detectable in the first postnatal period, shows a delayed onset, being detectable only at the adult stage. These findings seem to indicate that pre- and postnatal methylmercury exposure induces latent neurochemical and behavioral alterations which could last even after the clearance of the metal from the brain.

Animals↗

PubMed1993

Synthesis and antiinflammatory activity of 2,6-bis(1,1-dimethylethyl)phenol derivatives.

The influence of 11 newly synthesized 2,6-bis(1,1-dimethylethyl)phenol derivatives substituted in the 4 position as measured on the carrageenan paw edema assay in Sprague-Dawley rats, was studied using indomethacin as a reference drug. Furthermore we studied the possible interference of few of these compounds on the calcium binding sites by using the specific ligand [3H]-PN 200-110 in "in vitro" experiments. As far as regard the antiinflammatory activity only the compounds 2b, 2j and 2k, dosed at 20 mg/Kg/os, exerted an inhibitory effect on paw edema which was practically equal, after 6 h, to that of indomethacin (approximately 30%) dosed at 2.5 mg/Kg. The compound 2k, however, showed, in comparison with indomethacin and the other new tested compounds, a longer lasting effect, reaching, after 8 h, a 56.7% inhibition of the edema. Finally the above mentioned compounds, when tested alone or in combination with nitrendipine, did not exert any displacing activity on [3H]-PN 200-110 binding to synaptosomal membranes. It is noteworthy however that compound 2e, which incidentally was inactive as antiinflammatory agent, showed a negative allosteric modulatory activity on the ability of nitrendipine to displace [3H]-PN 200-110 binding.

Animals↗

PubMedDate not supplied

Effect of 2-methyltaurine and its enantiomers on arterial blood pressure.

Taurine has been shown to exert many biological effects. Among them, the ability of this amino acid to induce a reduction of arterial blood pressure, when administered intracerebroventricularly (i.c.v.) to mammals, has been established since a long time ago. To gain further information on the structure-activity requirements for taurine's hypotensive effect, the synthesis of 2-methyltaurine (2-aminopropanesulphonic acid) and the asymmetric synthesis of its enantiomers were performed; the enantiomeric purity of (R)- and (S)-2-methyltaurine was assayed by differential scanning calorimetry (DSC) and HPLC. The findings here reported show that the hypotensive effect elicited by the i.c.v. administration of racemate is mainly due to the (S)-enantiomer. The specificity of this effect was proved by the ability of the taurine antagonist TAG (6-aminomethyl-4H-3-methyl-1,2,4-benzothiadiazine 1,1-dioxide) to prevent it.

Animals↗