Double burden malnutrition of preschool children and its association with brain development and milk consumption

Protecting the quality of children growth and development becomes a supreme qualification for the betterment of a nation. Double burden child malnutrition is emerging worldwide which might have a strong influence to the quality of child brain development and could not be paid-off on later life. Milk places a notable portion during the infancy and childhood. Thus, the deep insight on milk consumption pattern might explain the phenomenon of double burden child malnutrition correlated to the cognitive impairments. Objective: Current study is intended (1) to examine the current face of Indonesian double burden child malnutrition: a case study in Bogor, West Java, Indonesia, (2) to investigate the association of this phenomenon with child brain development, and (3) to examine the contribution of socioeconomic status and milk consumption on this phenomenon so that able to formulate some possible solutions to encounter this problem. Design: A cross-sectional study using a structured coded questionnaire was conducted among 387 children age 5-6 years old and their parents from 8 areas in Bogor, West-Java, Indonesia on November 2012 to December 2013, to record some socioeconomic status, anthropometric measurements, and history of breast feeding. Diet and probability of milk intake was assessed by two 24 h dietary recalls and food frequency questionnaire (FFQ). Usual daily milk intake was calculated using Multiple Source Method (MSM). Some brain development indicators (IQ, EQ, learning, and memory ability) using Projective Multi-phase Orientation method was also executed to learn the correlation between double burden child malnutrition and some brain development indicator. Results and conclusions: A small picture of child double burden malnutrition is shown in Bogor, West Java, Indonesia, where prevalence of Severe Acute Malnutrition (SAM) is 27.1%, Moderate Acute Malnutrition (MAM) is 24.9%, and overnutrition is 7.7%. This phenomenon proves to impair the child brain development. The malnourished children, both under- and over- nourished children have significantly (P-value<0.05) lower memory ability compared to the normal children (memory score, N; SAM = 45.2, 60; MAM = 48.5, 61; overweight = 48.4, 43; obesity = 47.9, 60; normal = 52.4, 163). The plausible reasons behind these evidences are the lack of nutrient intake during the sprout growth period on undernourished children or increasing adiposity on overnourished children might influence the growth of hippocampus area which responsible to the memory ability. Either undernutrition or overnutrition, the preventive action on this problem is preferable to avoid ongoing cognitive performance loss of the next generation. Some possible solutions for this phenomenon are promoting breast feeding initiation and exclusive breast feeding practices for infants, supporting the consumption of a normal portion of milk (250 to 500 ml per day) for children, and breaking the chain of poverty by socioeconomic improvement. And, the national food security becomes the fundamental point for the betterment of the next. In the global context, the causes of under- and over- nutrition have to be opposed through integrated and systemic approaches for a better quality of the next generation of human beings.

Role of Rab5 in synaptic vesicle recycling

During synaptic transmission, NT-filled synaptic vesicles are released by Ca2+-triggered exocytosis at the active zone. Following exocytosis, SV membrane is immediately re-internalized and synaptic vesicles (SVs) are regenerated by a local recycling mechanism within the presynaptic terminal. It is debated whether an endosomal compartment is involved in this recycling process. In contrast, it is well known from cultured mammalian cells, that endocytic vesicles fuse to the early sorting endosome. The early endosome is a major sorting station of the cell where cargo is send into the degradative pathway to late endosome and lysosome or towards recycling. Each trafficking step is mediated by a certain protein of the Rab family. Rab proteins are small GTPases belonging to the Ras superfamily. They accumulate at their target compartments and have thereby been used as markers for the different endocytic organelles in cultured mammalian cells. Rab5 controls trafficking from the PM to the early endosome and has thereby been used as marker for this compartment. A second marker is based on the specific binding of the FYVE zinc finger protein domain to the lipid PI(3)P that is specifically generated at the early endosomal membrane. This study used the Drosophila NMJ as a model system to investigate the SV recycling process. In particular, three questions were addressed: First, is an endosomal compartment present at the synapse? Second, do SVs recycle through an endosome? Third, is Rab5 involved in SV recycling? We used GFP fusions of Rab5 and 2xFYVE to visualize endosomal compartments at the presynaptic terminal of Drosophila third instar larval NMJs. Furthermore, the endosomes are located within the pool of recycling SVs, labeled with the styryl-dye FM5-95. Using the temperature-sensitive mutation in Dynamin, shibirets, we showed that SV recycling involves trafficking through an intermediate endosomal compartment. In cultured mammalian cells, interfering with Rab5 function by expressing the dominant negative version, Rab5SN causes the fragmentation of the endosome and the accumulation of endocytic vesicles. In contrast, when Rab5 is overexpressed enlarged endosomal compartments were observed. In Drosophila, the endosomal compartment was disrupted when loss of function and dominant negative mutants of Rab5 were expressed. In addition, at the ultrastructural we observed an accumulation of endocytic vesicles in Rab5S43N expressing terminals and enlarged endosomes when Rab5 was overexpressed. Furthermore, interfering with Rab5 function using the dominant negative Rab5S43N caused a decrease in the SV recycling kinetics as shown by FM1-43 experiments. In contrast, overexpression of Rab5 or GFP-Rab5 caused an increase in the FM1-43 internalization rate. Finally, standard electrophysiological techniques were used to measure synaptic function. We found that the Rab5-mediated endosomal SV recycling pathway generates vesicles with a higher fusion efficacy during Ca2+-triggered release, compared to SVs recycled when Rab5 function was impaired. We therefore suggest a model in which the endosome serves as organelle to control the SV fusion efficacy and thereby the synaptic strength. Since changes in the synaptic strength are occuring during learning and memory processes, controlling endosomal SV recycling might be a new molecular mechanism involved in learning and memory.