Migration and nucleogenesis of mouse precerebellar neurons visualized by in utero electroporation of a green fluorescent protein gene

Neural migration is a critical step for accurate CNS development, but the molecular mechanisms that regulate migration, settlement and nucleogenesis remain largely unknown. The precerebellar neurons (PCNs), generated in the lower rhombic lip (LRL), migrate towards their destinations: some neurons form the pontine gray nucleus (PGN) and reticulotegmental nucleus (RTN) in the ipsilateral pons, while others form the lateral reticular and external cuneate nuclei in the contralateral medulla after crossing the midline. Here, by introducing an EGFP gene into a unilateral LRL of mouse embryos by in utero electroporation, we specifically labeled and tracked the PCNs in vivo. We found that a substantial number of the labeled neurons crossed the midline and formed PGN/RTN on the contralateral side. In addition, we found that a subpopulation of the interpolar subnucleus of the spinal trigeminal nucleus, which projects the axons to the cerebellum, was one of the PCNs derived from the LRL. Furthermore, because the electroporated mice were born and grew up healthy, we could visualize the PCNs and their mossy fibers in the adult brain. Therefore, the EGFP labeling of PCNs can be applied to studying the physiology of the mossy fiber system as well as PCN development in embryos.     

Effects of Combined Physical and Cognitive Exercises on Cognition and Mobility in Patients With Mild Cognitive Impairment: A Randomized Clinical Trial

Importance

Although participation in physical and cognitive activities is encouraged to reduce the risk of dementia, the preventive efficacy of these activities for patients with mild cognitive impairment is unestablished.

Generation of transgenic mice with elevated blood pressure by introduction of the rat renin and angiotensinogen genes.

The role of the renin-angiotensin system in blood pressure control and in the development of hypertension was investigated by generating transgenic mice carrying the rat renin or angiotensinogen gene or both genes under the control of the mouse metallothionein I promoter. The systolic blood pressure was significantly elevated in transgenic mice carrying both transgenes but was maintained normally in those bearing either of the transgenes. The transgene was effectively and properly transcribed to form the mature mRNA in the transgenic mice. The production of rat renin and angiotensinogen in the transgenic mice carrying the corresponding transgene was also verified by immunoanalyses of these proteins. Furthermore, the specific angiotensin-converting enzyme inhibitor captopril was effective in reducing the elevated blood pressure of the hypertensive transgenic mice. These results indicate that the combined action of the exogenous rat renin and angiotensinogen is responsible and necessary for elevation of blood pressure in the hypertensive transgenic mice.     

Depressive symptoms in older adults are associated with decreased cerebral oxygenation of the prefrontal cortex during a trail-making test

Growing evidence supports the relationships between depressive symptoms, cognitive decline, and brain structural changes in older adults. The purpose of this study was to determine whether depressive symptoms are related to cerebral oxygenation during cognitive tasks in older adults. In this study, 80 elderly subjects (73.9 ± 5.4 years, 34 males) were evaluated using multi-channel Near-infrared spectroscopy. Concentration changes (mmol cm/l) in oxy-hemoglobin (oxy-Hb), as the most reliable available indicator of changes in regional cerebral blood flow, in the right and left prefrontal cortex were measured during the Trail Making Test Part B (TMT-B). Depressive symptoms were assessed using the short Geriatric Depression Scale (GDS). Subjects were divided into a depressive group (GDS greater than or equal to 6) and non-depressive group (GDS lower than 6). In results, Oxy-Hb activation during the TMT-B was significantly smaller in the depressive group (n = 13) than in the non-depressive group (n = 67) in both the right and left prefrontal cortex. In the multivariate analysis, GDS scores were significantly negatively correlated with oxy-Hb activation after adjusting for age, gender and educational history (right, β = −0.32, p = 0.002; left, β = −0.25, p = 0.02). Less prefrontal activation in older adults with depressive symptoms may account for decline in executive function. Further studies are needed to investigate the influence of the less brain activation associated with depressive symptoms on future cognitive decline and structural brain changes in older adults.     

M-VAC chemotherapy for patients with lymph node metastases and/or locally advanced bladder carcinoma

Sixteen patients with lymph nodes metastases and/or locally advanced bladder carcinoma were treated with a combination chemotherapy regimen consisting of methotrexate, vinblastine, adriamycin, and cisplatin (M-VAC) from November 1986 through September 1988. There were 14 men and 2 women. The median age was 61.9 years, with a range from 43 to 81 years. Complete response (CR) was observed in 6 of 16 patients (38%), partial response (PR) was confirmed in 5 of 16 patients (31%), and overall response rate was 69%. Median duration of response was 10.3 and 5.2 months in CR and PR patients, respectively. The myelosuppression with this regimen was tolerable. This study demonstrates that the M-VAC regimen is effective in the invasive bladder carcinoma with or without lymph nodes metastases. However, the duration of response is relatively short, and the true long-term benefits of this regimen remain to be determined.     

Prolactin lowering effect of dihydroergokryptine in rat and in man

The prolactin lowering activity of dihydroergokryptine was investigated both in rats and in humans. The drug was administered orally at the doses of 0.2, 1 and 5 mg/Kg to intact or reserpinized male rats. Nine male adult volunteers were given 300 mg cimetidine iv 90 min after receiving 2, 3 or 4.5 mg of dihydroergokryptine and 3, 4.5 and 6.75 mg of dihydroergocristine or placebo per os in a randomized, cross-over design. Eight young adult males were injected im with 10 mg sulpiride 120 min after randomly receiving dihydroergokryptine 2.5 and 5 mg or placebo in a cross-over manner. Finally, five healthy young women were given dihydroergokryptine 2.5 and 5 mg, bromocriptine 2.5 mg and placebo in a cross-over design. Dihydroergokryptine caused a strong, long-lasting, dose-dependent fall of plasma prolactin concentrations in both rats and humans. Moreover, it inhibited the reserpine-induced rise of plasma prolactin in rats, as well as the cimetidine-or sulpiride-induced hyperprolactinemia in humans. Dihydroergokryptine proved twice as potent as dihydroergocristine and about half as potent as bromocriptine. Effective doses of both dihydrogenated ergot alkaloids were much better tolerated than bromocriptine.