Novel variants in outer protein surface of flavin-containing monooxygenase 3 found in an Argentinian case with impaired capacity for trimethylamine N-oxygenation.

Flavin-containing monooxygenase 3 (FMO3) is a polymorphic drug metabolizing enzyme associated with the genetic disorder trimethylaminuria. We phenotyped a white Argentinian 11-year-old girl by medical sensory evaluation. After pedigree analysis with her brother and parents, this proband showed to harbor a new allele p.

Inner Hair Cell and Neuron Degeneration Contribute to Hearing Loss in a DFNA2-Like Mouse Model.

DFNA2 is a progressive deafness caused by mutations in the voltage-activated potassium channel KCNQ4. Hearing loss develops with age from a mild increase in the hearing threshold to profound deafness. Studies using transgenic mice for Kcnq4 expressed in a mixed background demonstrated the implication of outer hair cells at the initial phase.

Septal grafts restore cognitive abilities and amyloid precursor protein metabolism.

Cortical cholinergic loss and amyloidogenic processing of the beta-amyloid precursor protein (APP), may functionally interact in Alzheimer's disease. However, it is still unknown whether biological restoration of regulatory cholinergic inputs affects APP metabolism in vivo. Rats immunolesioned with 192 IgG-saporin exhibited severe acquisition deficits in place navigation that were paralleled by a dramatic loss of terminal cholinergic innervation and by marked changes in the regional expression of APP-like immunoreactivity.

Muscarinic acetylcholine receptor knockout mice show distinct synaptic plasticity impairments in the visual cortex.

In the present report, we focused our attention on the role played by the muscarinic acetylcholine receptors (mAChRs) in different forms of long-term synaptic plasticity. Specifically, we investigated long-term potentiation (LTP) and long-term depression (LTD) expression elicited by theta-burst stimulation (TBS) and low-frequency stimulation (LFS), respectively, in visual cortical slices obtained from different mAChR knockout (KO) mice. A normal LTP was evoked in M(1)/M(3) double KO mice, while LTP was impaired in the M(2)/M(4) double KO animals.

Developmental modulation of synaptic transmission by acetylcholine in the primary visual cortex.

Despite the evidence that cortical synaptic organization and cognitive functions are influenced by the activity of the cholinergic system during postnatal development, so far no information is available on the effects produced by acetylcholine (ACh) on synaptic transmission. In the present article, we show that the ability of visual cortex slices to respond to ACh depends on postnatal age. In adulthood, ACh exerts mainly a facilitatory action on synaptic transmission, depressing field potential (FP) amplitude only if applied at high concentrations (millimolar range).

Reduction of GFAP induced by long dark rearing is not restricted to visual cortex.

A key component of the astrocyte cytoskeleton is the glial fibrillary acidic protein (GFAP), which plays an essential role in neuron/astrocyte interactions. Environmental conditioning, such as visual experience manipulation, can affect neuronal and/or glial plasticity in specific brain areas. Previous work from our laboratory showed that short light deprivation throughout the period of GFAP maturation does not influence the expression profile of GFAP in mouse visual cortex; however, it was strong enough to affect neuronal phenotype.

Acetylcholine modulates cortical synaptic transmission via different muscarinic receptors, as studied with receptor knockout mice.

The central cholinergic system plays a crucial role in synaptic plasticity and spatial attention; however, the roles of the individual cholinergic receptors involved in these activities are not well understood at present. In the present study, we show that acetylcholine (ACh) can facilitate or depress synaptic transmission in occipital slices of mouse visual cortex. The precise nature of the ACh effects depends on the ACh concentration, and is input specific, as shown by stimulating different synaptic pathways.

Alpha7 but not alpha4 AChR subunit expression is regulated by light in developing primary visual cortex.

In the present paper we analyzed the expression pattern of the alpha4 and alpha7 nicotinic acetylcholine receptor (nAChR) subunits in the rat visual cortex through postnatal development, to clarify whether their expression is developmentally regulated and whether eventual developmental changes are regulated by visual experience. We found that both alpha4 and alpha7 mRNA levels accumulate from postnatal day 12 (P12) before eye opening, to around P35. The immunohistochemical results indicated that both subunits are expressed throughout all cortical laminae, except layer I.