Methylphenidate alleviates cognitive dysfunction caused by early manganese exposure: Role of catecholaminergic receptors.

Environmental manganese (Mn) exposure is associated with impaired attention and psychomotor functioning, as well as impulsivity/hyperactivity in children and adolescents. We have shown previously that developmental Mn exposure can cause these same dysfunctions in a rat model. Methylphenidate (MPH) lessens impairments in attention, impulse control, and psychomotor function in children, but it is unknown whether MPH ameliorates these dysfunctions when induced by developmental Mn exposure.

Methylphenidate alleviates cognitive dysfunction from early Mn exposure: Role of catecholaminergic receptors.

Environmental manganese (Mn) exposure is associated with impaired attention and psychomotor functioning, as well as impulsivity/hyperactivity in children and adolescents. We have shown previously that developmental Mn exposure can cause these same dysfunctions in a rat model. Methylphenidate (MPH) lessens impairments in attention, impulse control, and sensorimotor function in children, but it is unknown whether MPH ameliorates these dysfunctions when induced by developmental Mn exposure.

Rapid forgetting of social learning in the Ts65Dn mouse model of Down syndrome: New evidence for hippocampal dysfunction.

The Ts65Dn mouse model of Down syndrome recapitulates the hallmark areas of dysfunction that characterize the human disorder, including impaired performance in tasks designed to tap hippocampus-dependent learning and memory. Unfortunately, performance in the water maze tasks most commonly used for this purpose can be affected by behavioral and/or physiological abnormalities characteristic of Ts65Dn mice (e.g.

The effect of manganese exposure in Atp13a2-deficient mice.

Loss of function mutations in the P-ATPase ATP13A2 are associated with Kufor-Rakeb Syndrome and Neuronal Ceroid Lipofuscinosis. While the function of ATP13A2 is unclear, in vitro studies suggest it is a lysosomal protein that interacts with the metals manganese (Mn) and zinc and the presynaptic protein alpha-synuclein. Loss of ATP13A2 function in mice causes sensorimotor deficits, enhanced autofluorescent storage material, and accumulation of alpha-synuclein.

Substrate specificity of prostate-specific membrane antigen.

A series of putative dipeptide substrates of prostate-specific membrane antigen (PSMA) was prepared that explored alpha- and beta/gamma-linked acidic residues at the P1 position and various chromophores at the P2 position, while keeping the P1' residue constant as L-Glu. Four chromophores were examined, including 4-phenylazobenzoyl, 1-pyrenebutyryl, 9-anthracenylcarboxyl-gamma-aminobutyryl, and 4-nitrophenylbutyryl. When evaluating these chromophores, it was found that a substrate containing 4-phenylazobenzoyl at the P2 position was consumed most efficiently.

Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates.

To explore for the existence of an auxiliary hydrophobic binding register remote from the active site of PSMA a series of phenylalkylphosphonamidate derivatives of glutamic acid were synthesized and evaluated for their inhibitory potencies against PSMA. Both the phenyl- and benzylphosphonamidates (1a and 1b) exhibited only modest inhibitory potency against. The phenethyl analog 1c was intermediate in inhibitory potency while inhibitors possessing a longer alkyl tether from the phenyl ring, resulted in markedly improved K(i) values.