Gestational Exposure to Sodium Valproate Disrupts Fasciculation of the Mesotelencephalic Dopaminergic Tract, With a Selective Reduction of Dopaminergic Output From the Ventral Tegmental Area
FRONTIERS IN NEUROANATOMY
Authors: Adam, Agota; Kemecsei, Robert; Company, Veronica; Murcia-Ramon, Raquel; Juarez, Iris; Gerecsei, Laszlo I.; Zachar, Gergely; Echevarria, Diego; Puelles, Eduardo; Martinez, Salvador; Csillag, Andras
Abstract
Gestational exposure to valproic acid (VPA) is known to cause behavioral deficits of sociability, matching similar alterations in human autism spectrum disorder (ASD). Available data are scarce on the neuromorphological changes in VPA-exposed animals. Here, we focused on alterations of the dopaminergic system, which is implicated in motivation and reward, with relevance to social cohesion. Whole brains from 7-day-old mice born to mothers given a single injection of VPA (400 mg/kg b.wt.) on E13.5 were immunostained against tyrosine hydroxylase (TH). They were scanned using the iDISCO method with a laser light-sheet microscope, and the reconstructed images were analyzed in 3D for quantitative morphometry. A marked reduction of mesotelencephalic (MT) axonal fascicles together with a widening of the MT tract were observed in VPA treated mice, while other major brain tracts appeared anatomically intact. We also found a reduction in the abundance of dopaminergic ventral tegmental (VTA) neurons, accompanied by diminished tissue level of DA in ventrobasal telencephalic regions (including the nucleus accumbens (NAc), olfactory tubercle, BST, substantia innominata). Such a reduction of DA was not observed in the non-limbic caudate-putamen. Conversely, the abundance of TH+ cells in the substantia nigra (SN) was increased, presumably due to a compensatory mechanism or to an altered distribution of TH+ neurons occupying the SN and the VTA. The findings suggest that defasciculation of the MT tract and neuronal loss in VTA, followed by diminished dopaminergic input to the ventrobasal telencephalon at a critical time point of embryonic development (E13-E14) may hinder the patterning of certain brain centers underlying decision making and sociability.
Development of low phenylalanine flour for phenylketonuric patient
JOURNAL OF FOOD PROCESSING AND PRESERVATION
Authors: Pandey, Shruti; Sunny, Aleena; Govindaraju, Karadka; Singh, Ravindra P.
Abstract
Phenylketonuria is an autosomal recessive genetic disorder due to the mutation in the phenylalanine hydroxylase (PAH) gene which results in the lower level of phenylalanine hydroxylase enzyme, hence the conversion of phenylalanine (Phe) to tyrosine does not take place and excess Phe takes an alternate pathway to produce phenylketones. This manuscript describes the attempts made toward the development of a gelatin-based multipurpose flour with other low-cost ingredients as the available food products for PKU patients in the market are very expensive and affordability becomes an issue for the patients. The flour is easily bakeable, friable, extrudable, and can be mixed with an adequate amount of water to make new products. The Phe content of the sample was 251.8 mg/100 g of flour which was well within the limits, as recommended by the WHO. The experimentally developed biscuits from the flour has low Phe content and is suitable for PKU patients. Some of the applications for proposed low phenylalanine flour for phenylketonuric patient could be as a diet supplement for the patient suffering from PKU. The key advantage of this multipurpose flour is the low cost of the flour having high nutritional value. The flour can be used for baking, extrusion, and frying purpose. The functional and sensory properties of the biscuit formulated from the flour, are in par with commercially available biscuits indicating its suitability for commercialization. Furthermore, work on improving the flour quality and other functional properties of the flour can be studied. Practical applications The present article focuses on the importance of diet supplement for the patient suffering from PKU. The important advantage of multipurpose flour is the low cost of the ingredients and high nutritional value. The functional and sensory properties were in par with commercially available biscuit indicating its suitability for consumption. Further work on improving the flour quality and other functional properties of the flour can also be studied.