Mice lacking proSAAS display alterations in emotion, consummatory behavior and circadian entrainment.

ProSAAS is a neuroendocrine protein that is cleaved by neuropeptide-processing enzymes into more than a dozen products including the bigLEN and PEN peptides, which bind and activate the receptors GPR171 and GPR83, respectively. Previous studies have suggested that proSAAS-derived peptides are involved in physiological functions that include body weight regulation, circadian rhythms and anxiety-like behavior. In the present study, we find that proSAAS knockout mice display robust anxiety-like behaviors in the open field, light-dark emergence and elevated zero maze tests. These mutant mice also show a reduction in cued fear and an impairment in fear-potentiated startle, indicating an important role for proSAAS-derived peptides in emotional behaviors. ProSAAS knockout mice exhibit reduced water consumption and urine production relative to wild-type controls. No differences in food consumption and overall energy expenditure were observed between the genotypes. However, the respiratory exchange ratio was elevated in the mutants during the light portion of the light-dark cycle, indicating decreased fat metabolism during this period. While proSAAS knockout mice show normal circadian patterns of activity, even upon long-term exposure to constant darkness, they were unable to shift their circadian clock upon exposure to a light pulse. Taken together, these results show that proSAAS-derived peptides modulate a wide range of behaviors including emotion, metabolism and the regulation of the circadian clock.

Successful management of an intraluminal superior sagittal sinus meningioma causing elevated intracranial pressure using gamma knife radiosurgery in subacute setting: A case report.

BACKGROUND: Gamma Knife stereotactic radiosurgery (GKRS) facilitates precisely focused radiation to an intracranial target while minimizing substantial off-target radiation in the surrounding normal tissue. Meningiomas attached to or invading the superior sagittal sinus may result in sinus occlusion and are often impossible to completely resect safely. The authors describe successful management of a patient with a meningioma located completely inside the posterior aspect of the superior sagittal sinus. CASE DESCRIPTION: A 46-year-old woman presented to the emergency department with progressive generalized headaches accompanied by worsening vision. The patient underwent a diagnostic brain magnetic resonance imaging which showed a solitary a 7 × 6 × 10 mm homogeneously contrast-enhancing lesion within the lumen of the posterior aspect of superior sagittal sinus without ventricular enlargement or peritumoral edema. The lesion was thought to be a meningioma radiographically. To evaluate the suspected increased intracranial pressure, a lumbar puncture was subsequently performed and demonstrated an opening pressure of 30 cm H2O. After drainage of 40 cc of CSF, the spinal closing pressure was 9 cm H2O. After failure of conservative management with acetazolamide, and determination of surgical inoperability due to the critical intraluminal location of the mass lesion, the patient underwent Gamma Knife radiosurgery. The 0.36 cc tumor was treated as an outpatient in the Perfexion® model Gamma Knife with a highly conformal and selective plan that enclosed the 3D geometry of the tumor with a minimal margin tumor dose of 14 gy at the 50% isodose. Three months after GKRS, the patient reported continued reduction in the frequency and severity of both her headaches and her visual disturbance. Ophthalmological consultation noted progressive resolution of her optic disc edema confirmed by formal optical coherence tomography. The patient is now 3 years out from GKRS with complete resolution of headache symptoms along with persistent reduction in tumor size (3 × 1 × 4 mm) on serial period imaging and resolution of papilledema. CONCLUSION: Tumors located in such critical anatomic regions, as in our patient, should be considered for primary GKRS when the risks of biopsy or removal are too high. GKRS was able to provide great radiographic and clinical result in an intricately located meningioma.