Affective disorders including depression and anxiety are among the most prevalent behavioral abnormalities in patients with Alzheimer's disease (AD), which affect the quality of life and progression of the disease. Dysregulation of the hypothalamic-pituitary-adrenal-(HPA) axis has been reported in affective disorders and AD. Recent studies revealed that current antidepressant drugs are not completely effective for treating anxiety- and depression-related disorders in people with dementia. ATP-sensitive-potassium-(K) channels are well-known to be involved in AD pathophysiology, HPA axis function and the pathogenesis of depression and anxiety-related behaviors. Thus, targeting of K channel may be a potential therapeutic strategy in AD. Hence, we investigated the effects of intracerebroventricular injection of Aβ25-35 alone or in combination with glibenclamide, K channel inhibitor on depression- and anxiety-related behaviors as well as HPA axis response to stress in rats. To do this, non-Aβ25-35- and Aβ25-35-treated rats were orally treated with glibenclamide, then the behavioral consequences were assessed using sucrose preference, forced swim, light-dark box and plus maze tests. Stress-induced corticosterone levels following forced swim and plus maze tests were also evaluated as indicative of abnormal HPA-axis-function. Aβ25-35 induced HPA axis hyperreactivity and increased depression- and anxiety-related symptoms in rats. Our results showed that blockade of K channels with glibenclamide decreased depression- and anxiety-related behaviors by normalizing HPA axis activity in Aβ25-35-treated rats. This study provides additional evidence that Aβ administration can induce depression- and anxiety-like symptoms in rodents, and suggests that K channel inhibitors may be a plausible therapeutic strategy for treating affective disorders in AD patients.

Blind access PCCL (without any ultrasonic or fluoroscopic guidance) is a facile and safe approach for removing stones in the pediatric bladder stones. Advantages include the lack of ionizing radiation, no need for opacification by iodine contrast media and low relative cost. We recommend this minimally invasive technique for management of large bladder stones (larger than 1 cm) in children. To our knowledge, this is the largest single-center series reported on percutaneous cystolithotripsy of endemic bladder stones in children.

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This work demonstrates a pain modulatory role of the orexinergic system via the PAG in hypothalamic-mediated analgesia suggesting that orexins can be advantageously targeted to achieve analgesia. WHAT DOES THIS STUDY ADD?: OX1 receptor antagonist (SB334867) administration into the ventrolateral periaqueductal gray matter (vlPAG) dose dependently blocked the carbachol-induced antinociception. CB1 receptor antagonist (AM251) microinjection in the vlPAG prevented carbachol-induced antinociception in a dose-dependent manner. Concurrent administration of SB334867 and AM251 into the vlPAG did not reinforce the antinociceptive responses.