Re: abstracts-VIP related & autism

[Guest guest]

From: <thecolemans4@...>

Date: Thu Jan 12, 2006 9:46 pm

Subject: Re: abstracts-VIP related neuroprotection

>Wow! This is a very big deal, isn't it? OMGoodness

I think it is....note the first abstract below and the levels of VIP & NT-3.

Then look at the other two abstracts-research from the scientists with

these new agents. (Brenneman, Gozes)

Down syndrome-NT-3 and CGRP were lower and VIP higher

autistic subjects-NT-3 levels were significantly lower than controls and an

increase in VIP approached statistical significance

(VIP) promotes neuronal differentiation through activity-dependent

neurotrophic factor

ADNF causes secretion of neurotrophin 3 (NT-3)

VIP-ADNF-NT-3 neuronal-glial pathway

Int J Dev Neurosci. 2005 Nov 12; [Epub ahead of print]

Selected neurotrophins, neuropeptides, and cytokines: developmental

trajectory and concentrations in neonatal blood of children with autism or

Down syndrome.

PG, Kuddo T, Song EY, Dambrosia JM, Kohler S, Satyanarayana G,

Vandunk C, Grether JK, KB.

National Institute of Child Health and Development, Building 31, Room 2A25,

Bethesda, MD 20892-2426, USA.

Using a double-antibody immunoaffinity assay (Luminex) and ELISA technology,

we measured concentrations of certain neurotrophins, neuropeptides, and

cytokines in pooled samples (one to three subjects per sample) eluted from

archived neonatal blood of children with later-diagnosed autism, Down

syndrome, very preterm birth, or term control infants. We also measured

analytes in blood from healthy adult controls. Case or control status for

infant subjects was ascertained by retrospective review of service agency

medical records.

We observed inhibitory substances in eluates from archived bloodspots,

especially marked for measurement of BDNF. Concentrations in control

subjects differed by age: BDNF rose markedly with age, while NT-3 and NT-4/5

concentrations were lower in adults than in newborn infants. IL-8

concentrations were higher in newborn infants, preterm and term, than in

adults.

Considered by diagnostic group, total protein was higher in Down syndrome

than in either autism or control subjects.

In infants with Down syndrome, concentrations of IL-8 levels were higher

than in controls, whether or not corrected for total protein; NT-3 and CGRP

were lower and VIP higher.

In samples from autistic subjects, NT-3 levels were significantly lower than

controls and an increase in VIP approached statistical significance.

Concentrations of NT-4/5 and CGRP were correlated in infants with autism but

not in Down syndrome or controls. Some of these results differ from earlier

findings using a single-antibody recycling immunoaffinity chromatography

(RIC) system.

We discuss interrelationships of VIP, NT-3 and IL-8 and their potential

relevance to features of the neuropathology of autism or Down syndrome.

PMID: 16289943 [PubMed - as supplied by publisher]

----------------------------------------

Exp Neurol. 2003 Sep;183(1):56-65.

Vasoactive intestinal peptide in the brain of a mouse model for Down

syndrome.

Hill JM, Ades AM, McCune SK, Sahir N, Moody EM, Abebe DT, Crnic LS,

Brenneman DE.

Section on Developmental and Molecular Pharmacology, NICHD, NIH, Bethesda,

MD 20892, USA. jh139h@...

The most common genetic cause of mental retardation is Down syndrome,

trisomy of chromosome 21, which is accompanied by small stature,

developmental delays, and mental retardation. In the Ts65Dn segmental

trisomy mouse model of Down syndrome, the section of mouse chromosome 16

most homologous to human chromosome 21 is trisomic. This model exhibits

aspects of Down syndrome including growth restriction, delay in achieving

developmental milestones, and cognitive dysfunction.

**Recent data link vasoactive intestinal peptide malfunction with

developmental delays and cognitive deficits. Blockage of vasoactive

intestinal peptide during rodent development results in growth and

developmental delays, neuronal dystrophy, and, in adults, cognitive

dysfunction.

**Also, vasoactive intestinal peptide is elevated in the blood of newborn

children with autism and Down syndrome.

In the current experiments, vasoactive intestinal peptide binding sites were

significantly increased in several brain areas of the segmental trisomy

mouse, including the olfactory bulb, hippocampus, cortex, caudate/putamen,

and cerebellum, compared with wild-type littermates. In situ hybridization

for VIP mRNA revealed significantly more dense vasoactive intestinal peptide

mRNA in the hippocampus, cortex, raphe nuclei, and vestibular nuclei in the

segmental trisomy mouse compared with wild-type littermates. In the

segmental trisomy mouse cortex and hippocampus, over three times as many

vasoactive intestinal peptide-immunopositive cells were visible than in

wild-type mouse cortex.

These abnormalities in vasoactive intestinal peptide parameters in the

segmental trisomy model of Down syndrome suggest that vasoactive intestinal

peptide may have a role in the neuropathology of Down-like cognitive

dysfunction.

PMID: 12957488 [PubMed - indexed for MEDLINE]

------------------------------------------------

J Neurosci. 2000 Nov 1;20(21):8012-20.

A glia-derived signal regulating neuronal differentiation.

Blondel O, Collin C, McCarran WJ, Zhu S, Zamostiano R, Gozes I, Brenneman

DE, McKay RD.

Laboratory of Molecular Biology, National Institute of Neurological

Disorders and Stroke, National Institutes of Health, Bethesda, land

20892, USA.

Astrocytes are present in large numbers in the nervous system, are

associated with synapses, and propagate ionic signals. Astrocytes influence

neuronal physiology by responding to and releasing neurotransmitters, but

the mechanisms that establish the close interaction between these cells are

not defined.

Here we use hippocampal neurons in culture to demonstrate that vasoactive

intestinal polypeptide (VIP) promotes neuronal differentiation through

activity-dependent neurotrophic factor (ADNF), a protein secreted by

VIP-stimulated astroglia.

ADNF is produced by glial cells and acts directly on neurons to promote

glutamate responses and morphological development.

ADNF causes secretion of neurotrophin 3 (NT-3), and both proteins regulate

NMDA receptor subunit 2A (NR2A) and NR2B.

These data suggest that the VIP-ADNF-NT-3 neuronal-glial pathway regulates

glutamate responses from an early stage in the synaptic development of

excitatory neurons and may also contribute to the known effects of VIP on

learning and behavior in the adult nervous system.

PMID: 11050122 [PubMed - indexed for MEDLINE]

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