The Long-Term Effects of Ethanol and Corticosterone on the Mood-Related Behaviours and the Balance Between Mature BDNF and proBDNF in Mice.

In this study, we aimed to establish the effects of chronic corticosterone (CORT) and ethanol administration on mood-related behaviour and the levels of mature brain-derived neurotrophic factor (mBDNF) and its precursor protein proBDNF in mice. C57BL6 male and female mice received drinking water (n = 22), 1% ethanol in drinking water (n = 16) or 100 µg/ml corticosterone in drinking water (containing 1% ethanol, n = 18) for 4.5 weeks. At the end of experimental protocol, the open field test (OFT) and elevated plus maze test were performed. Brain and adrenal tissues were collected and mBDNF and proBDNF were measured by ELISA assays. We found that the mice fed with corticosterone and ethanol developed anxiety-like behaviours as evidenced by reduced time in the central zone in the OFT compared with the control group. Both proBDNF and mBDNF were significantly decreased in the corticosterone and ethanol groups compared with the control group in the prefrontal cortex, hippocampus, hypothalamus and adrenal. The ratio of proBDNF/mBDNF in prefrontal cortex in the corticosterone group was increased compared with the ethanol group. Our data suggest that the ratio of proBDNF/mBDNF is differentially regulated in different tissues. Ethanol and corticosterone downregulate both mBDNF and proBDNF and alter the balance of proBDNF/mBDNF in some tissues. In conclusion, the ethanol and corticosterone may cause abnormal regulation of mBDNF and proBDNF which may lead to mood disorders.

[Downregulation of large conductance calcium-activated potassium channels in paraventricular nucleus contributes to sympathoexcitation in rats with chronic heart failure].

Objective: To elucidate the association between large conductance calcium-activated potassium channels (BKCa) in the paraventricular hypothalamic nucleus (PVN) and sympathetic outflow in rats with chronic heart failure (CHF) . Methods: Male Wistar rats (6-7 weeks old) were randomized to sham operated group and CHF group (coronary artery ligation) . Two weeks after operation, BKCa inhibitor Iberiotoxin (IBTX) was infused into PVN by osmotic minipumps, rats were divided into following groups: sham+aCSF, CHF+aCSF, sham+low dose IBTX (0.125 nmol/nl) , CHF+low dose IBTX, sham+moderate dose IBTX (1.25 nmol/nl) , CHF+moderate dose IBTX, sham+ high dose IBTX (12.5 nmol/nl) , and CHF+high dose IBTX (n=6 each) . Additional rats were grouped as follows: sham+vehicle, sham+KCNMB4 knockdown (by rAAV2-KCNMB4 shRNA virus injection in PVN) , CHF+vehicle, CHF+ KCNMB4 knockdown group (n=6 each) . The cardiac function was determined by echocardiography, left ventricular hemodynamics were measured invasively, renal sympathetic nerve activity (RSNA) was recorded at 6 weeks after coronary artery ligation or sham operation. The contents of norepinephrine (NE) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in plasma were determined by enzyme-linked immunosorbent assay. The protein and mRNA expression of KCNMB4 in PVN were measured by immunofluorescence staining, Western blot, and real-time PCR, mRNA expression of BKCa in PVN was detected by real-time PCR. Results: Compared with the sham operation group, the cardiac function of the heart failure group was significantly reduced (P<0.05) , and the plasma NE and the serum NT-proBNP were significantly elevated (P<0.05) . The protein and mRNA expression of KCNMB4 in PVN were obviously down-regulated in CHF rats (P<0.05) . After perfusion of IBTX or KCNMB4 knockdown by microinjection of rAAV2-KCNMB4 shRNA virus,right ventricular weight/body weight and lung weight/body weight ratio as well as left ventricular end-diastolic diameter were increased and left ventricular ejection fraction was decreased (all P<0.05) , the sympathetic driving indexes was increased in sham rats, changes of these parameters further aggravated in CHF rats (P<0.05) . KCNMB4 knockdown further downregulated protein expression in PVN of CHF rats. Conclusion: Downregulation and blunted function of BKCa in PVN may contribute to sympathoexcitation and deterioration of cardiac function in rats with chronic heart failure.

Effects of electro-acupuncture on the expression of c-jun and c-fos in spared dorsal root ganglion and associated spinal laminae following removal of adjacent dorsal root ganglia in cats.

This study evaluated the plastic changes of c-jun and c-fos in the right sixth lumbar dorsal root ganglion (L6 DRG), Rexed's lamina II in representative spinal segments L3, L5, and L6 and in the nucleus dorsalis (ND) at L3 segments after electro-acupuncture (EA) in cats subjected to removal of L1-L5 and L7-S2 DRG. Following dorsal root ganglionectomy, there was a significant increase in the density of c-jun immunoreactivity in the neurons and glia in spinal lamina II and in the ND; there was also marked elevation in the expression of c-fos in ND. In both cases there was no change in the c-jun and c-fos immunoreactivity in the DRG. After EA in the operated animals, there was an up-regulation in the expression of c-jun in the L6 DRG and the associated spinal lamina II; however, increased c-fos expression was detected only in the L6 DRG. Western blot and RT-PCR were also performed to quantitatively explore the mRNA and protein expression changes in the spinal dorsal horn and associated DRG. Following partial deafferentation, there was a significant increase in the protein level of both c-jun and c-fos in the dorsal horn, while, in both cases there was no change in c-jun and c-fos protein and mRNA in the DRG. After EA in the operated animals, both c-jun protein and its mRNA in the L6 DRG as well as the associated dorsal horn of L6 spinal segment were upregulated, but increased c-fos protein and its mRNA was observed only in the L6 DRG. These findings suggested that c-jun and c-fos might be related to the acupuncture promoted spinal cord plasticity as reported previously.

Cerebral infarction improved by safflower treatment.

The effect of safflower on cerebral infarction was studied in 152 Mongolian gerbils. Sixty-three animals were evaluated neurological deficit over 8 hours postoperation, then sacrificed and NE, DA and 5-HT contents of each cerebral hemisphere and brain stem were determined. NE, DA and 5-HT of hemisphere ipsilateral to the ligated artery in untreated animals declined significantly compared with sham-operated animals and safflower-treated gerbils. There was no significant difference between safflower-treated and sham-operated animals in NE, DA and 5-HT contents. The mean stroke index at 8 hours in safflower treated animals was 2.1 +/- 0.7, whereas untreated gerbils was 7.8 +/- 1.9 (P less than 0.01). Eighty-nine animals were followed up for 5 days, the safflower-treated animals showed a benign clinical course and mortality rate was reduced by 29.7% (6/34 vs. 26/55) in safflower-treated animals compared with untreated animals (P less than 0.01). Safflower has a protective and beneficial effect on cerebral ischemia induced in Mongolian gerbils.