Ultrastructural Evidence of Autophagy in Cerebral Capillary Pericytes in Notch3 Mutant Transgenic Mice.
Xin Gu, Xiaoyun Liu, Li-Ru Zhao. Louisiana State Universtiy at Shreveport
Background: Notch3 encodes a transmembrane receptor. Postnatal expression of Notch3 is predominantly in vascular smooth muscle cells (VSMCs) and pericytes. In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and in animal models, Notch3 mutation resulted in VSMC degeneration and the accumulation of granular osmiophilic material (GOM) in vascular walls. Notch3 mutation associated cerebral capillary pathology has not been described. We have studied the ultrastructural morphology of cerebral capillaries in aged Notch3 mutant transgenic mice and have identified evidence of autophagy (type 2 apoptosis) in capillary pericytes.
Design: Sections of brain from four controls and ten Notch3 mutant transgenic mice (22-month old) were fixed and sectioned for electron microscopy (EM) according to standard techniques. An average 20-40 capillaries in the cerebral cortex in each section were examined.
Results: In controls, no capillaries showed pericyte autophagy. In Notch3 mutant mice, 5-10% of the capillaries revealed pericyte autophagy. Different stages of autophagic vacuoles presented in these pericytes (figures 1, 2). No GOM was identified in the pericytes/vascular walls.
Conclusions: EM revealed autophagy in cerebral capillary pericytes in Notch3 mutant transgenic mice. To best of our knowledge, this is the first report to describe autophagy in the pericytes associated with Notch3 mutation. In contrast to previous studies of arterioles, there was no GOM accumulation in the pericytes and capillary walls. These findings suggest that abnormal Notch3 signaling results in type 2 apoptosis in cerebral capillary pericytes. Capillary pericyte autophagy may lead to capillary injury, microcirculatory dysfunction, hypoperfusion and white matter degeneration.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 285, Wednesday Morning