Spontaneous recovery of fear differs among early – late adolescent and adult male mice

Adolescence is a vulnerable period for developing anxiety-related mental disorders such as post-traumatic stress disorder (PTSD), which requires a long-term course of therapy when a traumatic event has been experienced during childhood. However, the biological mechanism underlying these age-dependent characteristics remains unclear. In the present study, we used early adolescent, late adolescent and adult (4-, 8-, and 15-week old) male mice to examine age differences in fear memory, fear extinction, and spontaneous recovery of fear. We also measured the activation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus (dHip) and the basolateral amygdala (BLA) following a spontaneous recovery test. Our major findings were as follows: (1) early adolescent and adult mice did not recover the fear response; only late adolescent mice recovered the fear response. (2) The ERK2 in the dHip was more activated after the spontaneous recovery test in late adolescent mice than in adult mice, and the ERK2 in the BLA was more activated after the spontaneous recovery test in adult mice than in late adolescent mice. These results suggest that there exists a unique period in which spontaneous recovery occurs and that these late adolescent behavioral signatures may be related to alteration in the ERK2 phosphorylation in the dHip and BLA.     

In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen,N,N-[11C]dimethyltryptamine

The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. [¹¹C]DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of [¹¹C]DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of [¹¹C]DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors.     

Effects of hypertension and type 2 diabetes mellitus on the risk of total cardiovascular events in Japanese patients with hypercholesterolemia: implications from the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia, hypertension, and diabetes mellitus (DM) are well-established risk factors for cardiovascular disease. We analyzed the cardiovascular events in hyperlipidemic patients with or without DM who were administered open-labeled simvastatin in groups stratified by blood pressure level using data from the Japan Lipid Intervention Trial (J-LIT). Hyperlipidemic patients with DM (n=6,288) had significantly more cardiovascular events than those without DM (n=33,933). The incidence rates of total cardiovascular events in the Non-DM and DM groups were 15.40 and 25.76 per 1,000 patients for the 6-year period, respectively. The relative risk of total cardiovascular events in the DM vs. the Non-DM group was 1.68, and the relative risk was significantly higher in the DM than in the Non-DM group. The relative risks of total cardiovascular events were significantly higher in DM and Non-DM patients whose systolic blood pressure (SBP) was greater than or equal to 130 mmHg compared to that of Non-DM patients whose SBP was less than 130 mmHg, and in DM and Non-DM patients whose diastolic blood pressure (DBP) was greater than or equal to 80 mmHg compared to that of Non-DM patients whose DBP was less than 80 mmHg. In all groups stratified by SBP and DBP, relative risks of total cardiovascular events were higher in DM patients than in Non-DM patients. For patients with hypercholesterolemia and DM, blood pressure should be strictly controlled in order to prevent both coronary events and stroke. These results are in good agreement with the JNC 7 and the ESH/ESC guidelines for DM patients, which recommended that the SBP and DBP be less than 130 and 80 mmHg, respectively.     

Retarded and distinct progress of lens opacification in congenic hereditary cataract mice, Balb/c-nct/nct

The Nakano cataract gene, nct, was introduced into Balb/c mice by repeated backcrosses to elucidate the possible effects of background genes on its expression. The resulting congenic Balb/c-nct/nct mice were characterized by retarded and sporadic cataract formation with a tendency of further retardation in males and by the different disease process of cataract as compared with Nakano mice. The age of 50% cataract incidence was 60 days in females and 90 days in males compared with 22 days in Nakano mice, and lens opacification commenced in a diffuse, mild form at the cortex in congenic but in a pin-head, intense form at the core in Nakano mice. Sex hormones seemed to be involved in the difference in cateractogenesis between male and female mice. Microphthalmia was slighter in degree in Balb/c background mice. The results indicated that the nct-dependent cataractogenesis may be influenced by background genes and some non-hereditary factors. Balb/c-nct/nct mice will provide a new type of hereditary cataract model.     

Effects of calmodulin antagonists on calcium-activated potassium channels in pregnant rat myometrium.

1. The effects of W-7, trifluoperazine, and W-5 on Ca2(+)-activated K(+)-channels were investigated with the inside-out patch-clamp method in smooth muscle cells freshly dispersed from pregnant rat myometrium. These drugs are known to have different potencies as calmodulin antagonists. 2. In the presence of 1 microM Ca2+ on the cytoplasmic side ([Ca2+]i), the fraction of time the channel was open (open probability, Po) was about 0.9 and the calmodulin antagonists (1-30 microM) applied to the cytoplasmic face reduced Po to 0.65-0.55 dose-dependently. In the presence of 0.1-0.16 microM Ca2+, when Po was very low (0.02), calmodulin antagonists increased Po. All antagonists used produced almost identical effects at the same concentration. 3. The probability density function of the open time distribution could be described by the sum of two exponentials. W-7 decreased the time constant of slow component of distribution and at 30 microM the slow component disappeared both at 1 and 0.25 microM [Ca2+]i, reflecting the appearance of flickering channel activity. The probability density function of the closed time distribution could be fitted with three exponentials. The time constants of these components were not significantly altered by W-7. 4. Internally applied calmodulin (1-5 microM) did not produce any significant effect on channel activity. 5. The effects of calmodulin antagonists are considered to be due to a direct action of these compounds on the channel, and suggest that channel activation by Ca2+ is not mediated by calmodulin.     

Inhibition of HIV-1 infectivity with curdlan sulfate in vitro

Polymethoxylated flavones and C-glycosyl derivatives isolated from medicinal plants besides other flavonoid compounds were studied for their influence on lipid peroxidation induced by FeSO4+ cysteine in rat liver microsomes. A number of hydroxyflavones (e.g. luteolin); C-glycosyl-flavones (e.g. orientin); methoxyflavones (e.g. gardenin D) and flavonols (e.g. datiscetin), as well as the flavanol leucocyanidol and the biflavone amentoflavone behaved as inhibitors of non-enzymic lipid peroxidation. Structure-activity relationships were established and it was observed that the structural features for active polyhydroxylated compounds were different from those of polymethoxylated flavones, antiperoxidative flavonoids possessing a high lipophilicity.     

Effect of dietary fiber on cytochrome P450IA1 induction in rat colonic mucosa.

The effect of dietary fiber on the induction of cytochrome P450IA1 in rat colonic mucosa after a single intragastric injection of 3-methylcholanthrene (3MC, 20 mg/kg) was investigated by examining the drug-metabolizing enzyme activity, immunoblotting for cytochrome P450IA1 and immunohistochemistry. 7-Ethoxycoumarin-O-deethylase activities were approximately 20-fold higher in microsomes from both proximal and distal portions of the colonic mucosa of control diet-fed 3MC-treated rats compared with those of control diet-fed untreated rats. Strong immunofluorescence for cytochrome P450IA1 was localized in the cytoplasm of the colonic mucosa surface epithelium from the control diet-fed 3MC-treated rats. 7-Ethoxycoumarin-O-deethylase activity and cytochrome P450IA1 content determined by immunoblotting were significantly lower in wheat bran-fed 3MC-treated rats than in control diet-fed 3MC-treated rats. Immunohistochemical analysis showed much weaker immunofluorescence for cytochrome P450IA1 in the surface epithelium of the colonic mucosa of the wheat bran-fed 3MC-treated rats. These observations suggested that dietary fiber can affect the induction of cytochrome P450IA1 in colonic mucosa by dietary inducers or carcinogens.