Effects of age and gender on white matter integrity.

BACKGROUND AND PURPOSE: DTI provides a sensitive measure of change in the microstructure of white matter integrity. The purpose of our study was to investigate age-related changes, sex differences, and age-by-sex interactions in white matter integrity (FA, AD, and RD) across the whole brain with a large sample. MATERIALS AND METHODS: A total of 857 healthy subjects (mean age = 56.1 ± 9.9 years; age range = 24.9-84.8 years) were included in this study. All subjects were scanned at 3T. With use of TBSS, we examined the effects of age and sex on FA, AD, and RD in the white matter. RESULTS: Global FA was negatively correlated with age (R(2) = 0.18, P < .0001), and global AD and RD were positively correlated with age (AD: R(2) = 0.02, P < .0001; RD: R(2) = 0.19, P < .0001). The correlation between age and global AD, however, was weak. Voxelwise analysis revealed a number of regions where FA was negatively correlated with age, with most of these regions showing a significant positive correlation between RD and age. There was a significant age-related FA increase in several white matter regions. Voxelwise analysis also revealed many regions where FA, AD, or RD differed between men and women; however, no region showed a significant interaction between age and sex. CONCLUSIONS: Our results suggest that age-related changes in white matter integrity are more strongly associated with myelin sheath degeneration than with axonal degeneration, and that, in some specific regions, the number of remyelinated axons might increase with age. Our results also suggest that there are no sex differences in the aging process of the white matter.

Behavioral effects of dilazep on cholinergic, dopaminergic, and purinergic systems in the rat.

This study examined the effects of 1,4-bis[3-(3,4,5-trimethoxy benzoyloxy)-propyl] perhydro-1,4-diazepine (dilazep; Comelian) on central dopaminergic, cholinergic, and purinergic neuronal systems in rats. Intraperitoneal injections of dilazep (1-5 mg/kg) produced yawning responses, the most effective dose being 2 mg/kg. Dilazep potentiated physostigmine-induced yawning but not pilocarpine- and bromocriptine-induced yawning. Dilazep-induced yawning was not affected by low doses of haloperidol or sulpiride, but was completely inhibited by atropine, a muscarinic M1 receptor antagonist. Dilazep-induced yawning, as well as physostigmine-induced yawning, were markedly inhibited by pretreatment with SK & F 38393, a dopamine D1 receptor agonist, and were potentiated by SCH23390, a dopamine D1 receptor antagonist that alone does not elicit yawning. Caffeine, an adenosine receptor antagonist, inhibited dilazep- and physostigmine-induced yawning responses but N6-cyclohexyl adenosine (CHA) and N6-(L-phenylisopropyl, adenosine (L-PIA), adenosine A1 receptor agonists, were inactive. These results suggest that because the effects of dilazep on central cholinergic neurons are similar to those of physostigmine dilazep may potentiate indirectly the action of endogenous acetylcholine. Cholinergic neurons activated by dilazep may be modulated by postsynaptic dopamine D1 receptor activity but may not be affected by dopamine D2 receptor activity. Furthermore, the stimulatory effects of dilazep on cholinergic neuron may not be due to an inhibition of dopamine D1 receptors via purinergic (adenosine A1 receptor) stimulation by dilazep.

[Effects of agonists and antagonists of benzodiazepine, GABA and NMDA receptors, on caffeine-induced seizures in mice].

In mice, tonic convulsive seizure induced by intravenous administration of caffeine (adenosine A1, A2 receptors antagonist) was significantly potentiated by any one of L-PIA (adenosine A1 receptor agonist), NECA (adenosine A2 receptor agonist) and 2-ClAd (adenosine A1, A2 receptors agonist). The caffeine-induced seizure was unaffected by diazepam (benzodiazepine receptor agonist), but was inhibited by Ro 15-1788 (antagonist or partial agonist). beta-DMCM (antagonist or inverse agonist) increased the seizure. Muscimol (GABA-a receptor agonist), baclofen (GABA-b receptor agonist) and AOAA (GABA transaminase inhibitor) did not show significant effect on caffeine-induced convulsion. Bicuculline (GABA-a receptor antagonist) and picrotoxin (chloride channel blocker) significantly potentiated the convulsion at the doses which did not induce it. Caffeine-induced convulsion was potentiated by NMDA with its non-convulsive dose. CPP (competitive NMDA receptor antagonist) and MK-801 (non-competitive NMDA receptor antagonist) significantly inhibited the seizures. These results suggest that caffeine-induced seizure is not caused by blockade of adenosine receptors. Caffeine may act to beta-carboline sensitive benzodiazepine receptor (Type 1) which has no linkage with GABA-a receptor. Furthermore, it is implied that caffeine plays some role at NMDA receptor calcium ion channel complex.