Smo-Shh signaling activator purmorphamine ameliorates neurobehavioral, molecular, and morphological alterations in an intracerebroventricular propionic acid-induced experimental model of autism.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disease characterized by cognitive and sensorimotor impairment. Numerous research findings have consistently shown that alteration of Smo-Shh (smoothened-sonic hedgehog) signaling during the developmental process plays a significant role in ASD and triggers neuronal changes by promoting neuroinflammation and apoptotic markers. Purmorphamine (PUR), a small purine-derived agonist of the Smo-Shh pathway, shows resistance to hippocampal neuronal cell oxidation and decreases neuronal cell death. The goal of this study was to investigate the neuroprotective potential of PUR in brain intoxication induced by intracerebroventricular-propionic acid (ICV-PPA) in rats, with a focus on its effect on Smo-Shh regulation in the brain of rats. In addition, we analyze the impact of PUR on myelin basic protein (MBP) and apoptotic markers such as Caspase-3, Bax (pro-apoptotic), and Bcl-2 (anti-apoptotic) in rat brain homogenates. Chronic ICV-PPA infusion was administered consecutively for 11 days to induce autism in rats. In order to investigate behavioral alterations, rats were tested for spatial learning in the Morris Water Maze (MWM), locomotive alterations using actophotometer, and beam crossing task, while Forced Swimming Test (FST) for depressive behavior. PUR treatment with 5 mg/kg and 10 mg/kg (i.p.) was administered from day 12 to 44. Besides cellular, molecular and neuroinflammatory analyses, neurotransmitter levels and oxidative markers have also been studied in brain homogenates. The results of this study have shown that PUR increases the level of Smo-Shh and restores the neurochemical levels, and potentially prevents morphological changes, including demyelination.

Molecular cloning, expression and chromosomal localization of a human gene encoding a 33 kDa putative metallopeptidase (PRSM1).

The zincins are a superfamily of structurally-related Zn(2+)-binding metallopeptidases which play a major role in a wide range of biological processes including pattern formation, growth factor activation and extracellular matrix synthesis and degradation. In this paper we report the identification and complete primary structure of a novel 33 kDa protein which contains the zinc-binding HEXXH motif found in the zincin superfamily. We have named this novel protein PRSM1 (PRoteaSe, Metallo, number 1). The gene was identified by the immunoscreening of a human placental cDNA library using polyclonal antibodies raised to the 70 kDa human matrix metalloendopeptidase, type III procollagen N-proteinase [Halila, R. and Peltonen, L. (1986) Purification of human procollagen type III N-proteinase from placenta and preparation of antiserum. Biochem. J. 239, 47-52]. The protein is found in placenta and cultured osteosarcoma cells. PRSM1 could share sequence homology with the type III procollagen N-proteinase. The prsm1 gene is represented once in the human genome and is localized on chromosome 16 (q24.3).

Effect of short term vitamin A deficiency on organ weights, blood glucose and lactate levels and, tissue protein and glycogen contents of albino rats: a preliminary study.

The effect of short term dietary vitamin A deficiency in post-pubertal female rats in terms of weight gain, food consumption, organ weights, haemoglobin content, blood glucose and lactate levels and, tissue protein and glycogen contents has been evaluated to gain insight into the possible interrelationship between vitamin A and general metabolism. Significant elevation in blood glucose level and reduction in blood lactate and haemoglobin along with a tendency of reduction in weights of spleen, adrenals and ovaries have been noted. Lowered tissue protein and glycogen contents and reduced body weight gain have also been revealed. Obviously, reduced functional competence of some of the organs and certain alterations in general metabolism especially of carbohydrates are suspected and hence is discussed in relation to supportive evidences available.

Effect of cholinesterase inhibitors on acetylcholine and insulin induced glucose uptake and certain hepatic enzymes in pigeon liver: an in vitro study.

Insulin and acetylcholine (ACh) are both known to promote glucose uptake by liver of birds. Acetylcholine induced glucose uptake can be predictably potentiated by inhibiting acetylcholinesterase activity. Monocrotophos, acothione (organophosphorus compound) and prostigmine are known inhibitors of acetylcholinesterase (AChE). In the present study the action of these three inhibitors of AChE alone as well as in combination with insulin and acetylcholine on in vitro glucose uptake by pigeon liver slices was investigated. Both organophorus compounds potentiated the action of insulin as well as acetycholine mediated glucose uptake by liver slices while prostigmine had inhibitory influence. The three compounds also induced alterations in enzyme activities in the liver slices. These results are discussed in detail in the text.

Effect of ACTH on glucose uptake by hepatic cells and its effect on hepatic enzymes in presence of insulin and acetylcholine.

An intrinsic hypoglycaemic activity has been attributed to ACTH. This action of ACTH is essentially mediated by increased insulin secretion. In the present study, the direct action of ACTH on glucose uptake by pigeon hepatocytes has been studied by in vitro technique. The results have shown that ACTH has a direct influence on glucose uptake and this action is not additive in presence of insulin. Glucose uptake in presence ACTH with Acetylcholine was not any more than what was obtained with ACTH alone. These observations have been taken to indicate a non-existence of synergistic action of ACTH with insulin or acetylcholine in promoting glucose uptake by avian liver cells.