Deficiency of aminopeptidase P1 causes behavioral hyperactivity, cognitive deficits, and hippocampal neurodegeneration.

Metabolic diseases affect various organs including the brain. Accumulation or depletion of substrates frequently leads to brain injury and dysfunction. Deficiency of aminopeptidase P1, a cytosolic proline-specific peptidase encoded by the Xpnpep1 gene, causes an inborn error of metabolism (IEM) characterized by peptiduria in humans. We previously reported that knockout of aminopeptidase P1 in mice causes neurodevelopmental disorders and peptiduria. However, little is known about the pathophysiological role of aminopeptidase P1 in the brain. Here, we show that loss of aminopeptidase P1 causes behavioral and neurological deficits in mice. Mice deficient in aminopeptidase P1 (Xpnpep1-/- ) display abnormally enhanced locomotor activities in both the home cage and open-field box. The aminopeptidase P1 deficiency in mice also resulted in severe impairments in novel-object recognition, the Morris water maze task, and contextual, but not cued, fear memory. These behavioral dysfunctions were accompanied by epileptiform electroencephalogram activity and neurodegeneration in the hippocampus. However, mice with a heterozygous mutation for aminopeptidase P1 (Xpnpep1+/- ) exhibited normal behaviors and brain structure. These results suggest that loss of aminopeptidase P1 leads to behavioral, cognitive and neurological deficits. This study may provide insight into new pathogenic mechanisms for brain dysfunction related to IEMs.

Effect of reductions in biomass fuel exposure on symptoms of sleep apnea in children living in the peruvian andes: a preliminary field study.

BACKGROUND: Multiple studies have evaluated the prevalence of sleep apnea in pediatric populations. Although environmental exposures to cigarette smoke (ECS) increase the risk of habitual snoring, no studies have thus far examined the potential contribution of indoor pollution in children. OBJECTIVE: To determine the frequency of symptoms associated with sleep apnea in children exposed to traditional wood-burning stoves to open fire, and assess whether symptoms subside following implementation of improved less environmentally contaminating stoves. METHODS AND MATERIALS: Residents of the communities of Chucllapampa, Sayhuapata, and Alparcuna in Cangallo province, department of Ayacucho, Peru were surveyed on two occasions within 12 months before and after the installation of an improved Inkawasi wood stove. The frequency of symptoms associated with sleep apnea was assessed in all children <15 years of age using a previously validated questionnaire. RESULTS: Parents of 59 children (62.7% males; mean age 7.76 ± 4.2 years) were interviewed representing >97% of the children in those small villages. The most common symptoms included nighttime awakenings, habitual snoring, repetitive movements during sleep, nasal congestion, and sore throat. After implementation of improved stoves in the homes, snoring (52.5% vs. 18.2%, P < 0.0001) nasal congestion (33.9% vs. 1.8%, P < 0.0001), behavioral hyperactivity (28.8% vs. 3.8%, P < 0.002), nighttime awakenings (42.4% vs. 1.7%, P < 0.0001), sore throat (38.2% vs. 5.5% P < 0.0001), breathing through the mouth during the day (33.9% vs. 1.8%, P < 0.001), daytime sleepiness (21.1% vs. 1.8%, P < 0.003), and falling asleep at school (14.6% vs. 0%, P < 0.03) were all significantly improved. CONCLUSIONS: Children exposed to traditional biomass fuel stoves had a higher frequency of symptoms related to sleep apnea, which decrease with improvements in biomass pollution.