Complement-dependent loss of inhibitory synapses on pyramidal neurons following Toxoplasma gondii infection.

The apicomplexan parasite Toxoplasma gondii has developed mechanisms to establish a central nervous system infection in virtually all warm-blooded animals. Acute T. gondii infection can cause neuroinflammation, encephalitis, and seizures. Meanwhile, studies in humans, nonhuman primates, and rodents have linked chronic T. gondii infection with altered behavior and increased risk for neuropsychiatric disorders, including schizophrenia. These observations and associations raise questions about how this parasitic infection may alter neural circuits. We previously demonstrated that T. gondii infection triggers the loss of inhibitory perisomatic synapses, a type of synapse whose dysfunction or loss has been linked to neurological and neuropsychiatric disorders. We showed that phagocytic cells (including microglia and infiltrating monocytes) contribute to the loss of these inhibitory synapses. Here, we show that these phagocytic cells specifically ensheath excitatory pyramidal neurons, leading to the preferential loss of perisomatic synapses on these neurons and not those on cortical interneurons. Moreover, we show that infection induces an increased expression of the complement C3 gene, including by populations of these excitatory neurons. Infecting C3-deficient mice with T. gondii revealed that C3 is required for the loss of perisomatic inhibitory synapses. Interestingly, loss of C1q did not prevent the loss of perisomatic synapses following infection. Together, these findings provide evidence that T. gondii induces changes in excitatory pyramidal neurons that trigger the selective removal of inhibitory perisomatic synapses and provide a role for a nonclassical complement pathway in the remodeling of inhibitory circuits in the infected brain.

Early neonatal hypoglycemia in exclusively breastfed babies in a developing country - India.

Background: Neonatal hypoglycemia has been a cause for concern due to increasingly frequent reports of long-term sequelae, leading to undue concern and inadvertent administration of formula feeds. Though hypoglycemia is usually encountered only in neonates with classical risk factors, hypoglycemia is also rarely seen even in babies with no known risk factors. These babies may present only with sequelae in later childhood. Methods: This is a hospital-based observational, prospective study. We included 299 exclusively breastfed neonates who were shifted to mother's side with no congenital malformation or need for neonatal intensive care unit (NICU) admission. The neonates were studied in two groups: " At Risk" and "No Risk." The "At Risk" group included babies with known risk factors like low birth weight, late preterm (34-36 weeks), small for gestational age (birth weight <10th centile), infant of a diabetic mother, or large for gestational age (birth weight >90th centile). Hypoglycemia was the primary outcome measured independent of feeding time for both groups. For the "At Risk" group, monitoring was done at 0, 1, 2, 3, 4, 12, 24 plus 48 h. For the "Not At Risk" group, it was done at 12 and 24 h of life. The factors associated with both groups were studies as the secondary outcome. Results and Conclusion: Out of 299 exclusively breastfed neonates, 13% were hypoglycemic. 27.06% were hypoglycemic in the "At Risk" group. In the "At Risk" group, low birth weight and primiparity were significant risk factors. The incidence of hypoglycemia in the "No Risk" group was 1.80%. Breast problems and breastfeeding problems, low education status of mother, young age, and primiparity were significant risk factors in the "No Risk" group.