Motor neurons with differential vulnerability to degeneration show distinct protein signatures in health and ALS.

The lethal disease amyotrophic lateral sclerosis (ALS) is characterized by the loss of somatic motor neurons. However, not all motor neurons are equally vulnerable to disease; certain groups are spared, including those in the oculomotor nucleus controlling eye movement. The reasons for this differential vulnerability remain unknown. Here we have identified a protein signature for resistant oculomotor motor neurons and vulnerable hypoglossal and spinal motor neurons in mouse and man and in health and ALS with the aim of understanding motor neuron resistance. Several proteins with implications for motor neuron resistance, including GABAA receptor α1, guanylate cyclase soluble subunit alpha-3 and parvalbumin were persistently expressed in oculomotor neurons in man and mouse. Vulnerable motor neurons displayed higher protein levels of dynein, peripherin and GABAA receptor α2, which play roles in retrograde transport and excitability, respectively. These were dynamically regulated during disease and thus could place motor neurons at an increased risk. From our analysis is it evident that oculomotor motor neurons have a distinct protein signature compared to vulnerable motor neurons in brain stem and spinal cord, which could in part explain their resistance to degeneration in ALS. Our comparison of human and mouse shows the relative conservation of signals across species and infers that transgenic SOD1G93A mice could be used to predict mechanisms of neuronal vulnerability in man.

Poststreptococcal glomerulonephritis in children: clinicopathological correlations and long-term prognosis.

Between 1962 and 1970, 36 children with acute biopsy-proven poststreptococcal glomerulonephritis (PSGN) entered a prospective long-term follow-up study. The initial biopsies were scored into four histological grades using criteria based on endocapillary proliferation, leucocyte infiltration, epithelial "hump" and crescent formation; 5 patients had grade-1 (least severe), 14 grade-2, 15 grade-3 and 2 grade-4 biopsies. Two children died from rapidly progressive glomerulonephritis; both had grade-4 biopsies. Early repeat biopsy in 12 patients showed improvement in all but one patient who progressed from grade 2 to type 2 mesangiocapillary glomerulonephritis (MCGN). The initial biopsy grade correlated significantly with heavy proteinuria (chi2 = 9.73, P less than 0.01) but not with hypertension, haematuria or renal functional impairment. Follow-up observations were made after mean periods of 9.5 years (range 5.4-12.4 years; 32 subjects) and 19.0 years (range 14.6-22 years; 30 subjects). None of the survivors had an abnormal plasma creatinine. Only one patient (grade-3 biopsy), a female with a subsequent history of recurrent pyelonephritis, was hypertensive. Isolated microscopic haematuria persisted in 1 grade-2 and 2 grade-3 subjects. One grade-2 subject had proteinuria secondary to MCGN and one grade-3 subject had mild proteinuria and borderline hypertension. Although 20% of subjects had urinary abnormalities, we conclude that the long-term outcome of PSGN in children is excellent.