STXBP1: the second synaptic vesicle release gene involved in epilepsy

De novo mutations in the gene encoding STXBP1 (MUNC18‐1) cause early infantile epileptic encephalopathy
Saitsu et al. (2008)
Nature Genetics 40: 782–788     

SLEEP CYCLES AND SKIN POTENTIAL IN NEWBORNS STUDIED WITH A SIMPLIFIED OBSERVATION AND RECORDING SYSTEM

A simple visual observation system, supplemented by measurement of skin potential, was devised for developmental studies of sleep cycles in settings where multiple electrode placement is not practicable. The findings replicated essential features of quiet and active sleep cycles which had been reported previously to exist against the background of decreasing level of physiological arousal, as sleep proceeds. Twelve newborns showed approximately one-half of their inter-feeding sleeping time in the rapid eye movement stage of sleep. Skin potential rapidly declined from the waking level, continued to decrease in level throughout sleep, increased in variability during REM sleep, and increased in level at the second waking period.     

Antibodies against the extracellular enveloped virus B5R protein are mainly responsible for the EEV neutralizing capacity of vaccinia immune globulin

In the event of smallpox bioterrorism, widespread vaccination may be required. Vaccinia immune globulin (VIG) has been used to treat complications from the smallpox vaccine. While the potency of VIG was defined by its ability to neutralize intracellular mature virus, a second form of vaccinia called the extracellular enveloped virus (EEV) is critical for virus spread in the host. The B5R-protein is one of many EEV-specific proteins. Immunoprecipitation and ELISA revealed that VIG recognizes the B5R-protein. An EEV plaque-reduction assay using a recombinant vaccinia that lacks the majority of the extracellular domain of B5R showed that the ability of VIG to neutralize EEV is principally directed at B5R. In addition, absorbing out the anti-B5R antibody present in VIG through the addition of recombinant B5R protein abrogated VIG's ability to significantly neutralize wild-type EEV. This work demonstrates the prominent role of B5R as a target of EEV-neutralizing activity of human antibodies.     

Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs) mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff) mice succumb to a profound neurodegenerative disease by 4-6 months of age. Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. We suggest that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.      

Substance P-immunoreactive nerves in the rat kidney

Previously published data have indicated that in the rat, unlike other species examined, the kidney is not supplied by sensory nerves containing substance P (SP). As part of a study of reflex control of renal function in the rat, we have now reassessed this situation. Many fine, varicose, SP-immunoreactive nerve fibers were found in the wall of the proximal ureter and the renal pelvis, and around the larger renal blood vessels. Sparser populations of similar nerves were also seen running close to proximal and distal tubules in the renal cortex. Occasional fibers were seen at the margins of the glomeruli. Our findings suggest that sensory nerves containing SP may carry sensory information of several types from the rat kidney.     

Different patterns of immunolocalization of calcitonin gene-related peptide and substance P in sympathetic ganglia of normotensive and genetically hypertensive rats

Calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity were investigated in the superior cervical ganglion of normotensive and genetically hypertensive Otago Wistar rats by an immunoperoxidase method. CGRP- and SP-positive varicose axons invested separate subpopulations of ganglion cells, neither of which contained neuropeptide Y. The densities of CGRP axons were similar in normotensive and hypertensive rats while the numbers of SP axons were several times higher in the hypertensive strain. Decentralization of the ganglion or chronic capsaicin treatment removed all immunoreactive terminals, indicating that both axon populations are likely to be collaterals from thoracic sensory afferents.