Phosphoinositide 3-Kinase Is Integral for the Acute Activity of Leptin and Insulin in Male Arcuate NPY/AgRP Neurons.

Neuropeptide Y (NPY)/Agouti-related protein (AgRP) neurons in the arcuate nucleus of the hypothalamus are part of a neuroendocrine feedback loop that regulates feeding behavior and glucose homeostasis. NPY/AgRP neurons sense peripheral signals (including the hormones leptin, insulin, and ghrelin) and integrate those signals with inputs from other brain regions. These inputs modify both long-term changes in gene transcription and acute changes in the electrical activity of these neurons, leading to a coordinated response to maintain energy and glucose homeostasis. However, the mechanisms by which the hormones insulin and leptin acutely modify the electrical activity of these neurons remain unclear. In this study, we show that loss of the phosphoinositide 3-kinase catalytic subunits p110α and p110ß in AgRP neurons abrogates the leptin- and insulin-induced inhibition of AgRP neurons. Moreover, continual disruption of p110α and p110ß in AgRP neurons results in increased weight gain. The increased adiposity was concomitant with a hypometabolic phenotype: decreased energy expenditure independent of changes in food intake. Deficiency of p110α and p110ß in AgRP neurons also impaired glucose homeostasis and insulin sensitivity. In summary, these data highlight the requirement of both p110α and p110ß in AgRP neurons for the proper regulation of energy balance and glucose homeostasis.

A review of current evidence in the surgical treatment of migraine headaches.

SUMMARY: Migraines affect 18% of women and 6% of men and result in an estimated $1 billion in medical costs and $16 billion productivity loss in the United States annually. Migraine headaches persist as a problem of this scale because pharmacologic treatments for migraines are frequently incompletely effective, resulting in a population of patients with significant residual disability. In the last decade, novel approaches to the treatment of migraines have been developed based on the theory that extracranial sensory branches of the trigeminal and cervical spinal nerves can be irritated, entrapped, or compressed at points throughout their anatomic course, ultimately leading to the cascade of physiologic events that results in migraine. Botulinum toxin (Botox) injection and surgical decompression of these trigger points have been shown to reduce or eliminate migraines in patients who are incompletely treated by traditional medical management. Despite the recent advances made with Botox, this treatment strategy most commonly results in only temporary migraine prevention. However, the evidence supporting the efficacy and safety of permanent surgical decompression of peripheral trigger points is accumulating rapidly, and the overall success rate of surgery has approached 90%. In addition, an abundance of literature investigating the precise anatomical dissections associated with trigger points has been published concurrently. This article reviews the most up-to-date clinical and anatomic evidence available and seeks to provide a comprehensive, concise resource for the current state of the art in the surgical treatment of migraine headaches.