Measurement of arylesterase enzymatic activity and assessment of genetic polymorphisms located in the PON1 gene as a diagnostic tool in autism-spectrum disorders

The present invention concerns a method for detecting the presence of or predisposition to autism, an autism spectrum disorder, or an autism-associated disorder in a subject, the method comprising measuring an arylesterase enzymatic activity in a sample from the subject, optionally combined with the determination of alleles of PON1 polymorphisms

DOPAMINERGIC GENE-EXPRESSION DURING AMPHETAMINE WITHDRAWAL

Animals and humans display a constellation of behavioral and neurochemical signs after termination of psychostimulant administration. Amphetamine withdrawal could involve the dopaminergic systems that are thought to underlie psychostimulant rewarding effects, and may thus conceivably alter expression of key genes for dopaminergic transmission, including those encoding tyrosine hydroxylase (TH), the membrane dopamine transporter (DAT) and the synaptic vesicle amine transporter (SVAT). Withdrawal from 7.5 mg kg-1 i.p. amphetamine (b.i.d. for a two week duration) yields no significant changes in rat DAT mRNA. TH mRNA levels are modestly enhanced over the same week of withdrawal, during which dopamine levels and behavioral novelty responses are both depressed. SVAT expression is significantly blunted following chronic amphetamine treatment. Altered TH and/or SVAT gene expression might contribute to restoring normal function to neurons "withdrawing" from amphetamine treatments

BDNF and NT-3 applied in the whisker pad reverse cortical changes after peripheral deafferentation in neonatal rats

It has been known for a long time that subcortical input drives the specification of cortical areas. Molecular signals mediating this instructive effect from the periphery are poorly understood. In foetal or neonatal rats, ablation of whisker follicles, transection of the infraorbital nerve, inhibition of axonal transport, but not impulse activity blockade, prevent formation of barrels in the primary somatosensory cortex (S1). These findings suggest that a chemical signal, possibly arising from the skin or the follicle, may be responsible for somatotopic pattern formation in S1. Neurotrophins promote survival and differentiation of primary sensory neurons, and are expressed in the whisker pad during development. Neonatal rats received gelfoam impregnated with NGF, BDNF or NT-3 under the whisker pad following surgical denervation of whisker rows D and E on P0. Barrel formation in S1 was assessed on P7 by acetylcholinesterase histochemistry and 5-HT-immunohistochemistry. BDNF and NT-3, but not NGF, promoted development of the cortical barrels corresponding to denervated whiskers. Furthermore, BDNF and NT-3 prevented the lesion-induced expansion of row C barrels, while NGF appeared to promote row C expansion. Our results suggest that BDNF and NT-3 arising from the whisker pad are involved in the formation and/or maintenance of the barrel pattern in S1. These findings are potentially relevant for the prevention of sensory disturbances possibly due to reorganization of central sensory circuits after peripheral nerve lesions in humans