Presynaptic markers

Early postmortem neurochemical studies suggested reductions in presynaptic markers for the GABAergic neurons, such as glutamatic acid decarboxalase (GAD) activity, in prefrontal cortex in schizophrenic subjects... 

Glutamate Decreased presynaptic markers Decreased HC AMPA and kainate receptor expression Minor changes in FC NMDA R sub-units Altered glutamate fibres in cingulate cortex NMDA receptor antagonists produce schizophrenia-like psychosis Roles of NMDA receptors in development and neurotoxicity Partial NMDA receptor agonists have some therapeutic benefits... 

Reduced dysbindin-1 gene expression in dorsolateral prefrontal cortex (DLPFC) and hippocampal formation (HF) of schizophrenia cases studied with in situ hybridization. Asterisks in histograms indicate a significant difference between controls (darker bars) and schizophrenia cases (lighter bars). DLPFC reductions in dysbindin-1 (a) were found in all cell layers in the absence of any changes in the presynaptic marker synaptophysin (d) or the postsynaptic marker spinophilin A (g). The reductions found in the HF occurred in all areas except CA1. Graphs are accompanied by representative sections from normal (b, e, h, and k) and schizophrenia (c, f, i, and I) cases. Adapted from Weickert et al. (2004) for the DLPFC and Weickert et al. (2008) for the HF... 

Synapse formation and maturation in different in vitro models can be evaluated by immune-staining of presynaptic markers (e.g., synaptophysin and synapsin) [93] and postsynaptic markers (e.g., postsynaptic density protein-95 (PSD-95) and 41 IB) [94], Moreover, neurotransmitter release can be studied by measuring the uptake and release of fluorescent dyes during presynaptic activity (e.g., FM1-43) [95], In spontaneously electrically active in vitro models, electrophysiological techniques can be another option to evaluate the neuronal network development and functional synapses (see paragraph below). Any disturbance of the synaptogenesis process and function induced by chemical exposure would most likely alter the electrical activity that can be used as a sensitive readout for in vitro DNT/neurotoxicity evaluation [12, 96]. 

Neurochemical examination of biopsy and antopsy brain material from Alzheimer patients has revealed loss of the presynaptic marker enzymes acetyl coenzyme A (acetyl-CoA), chohne 6>-acetyltransferase and acetylcholinesterase (AChE), and of muscarinic receptor sites of the M2 subtype correlating with dementia score and severity of nenrohistopathology [8]. These alterations do, to some extent, reflect the well-documented neuronal cell loss in the nucleus of Meynert in presenile dementia and AD. Lesions of this brain nncleus in rats, a limited model for the cholinergic deficit of AD, resnlt in marked reductions in the levels of cholinergic en me markers in the neocortex accompanied by great decreases in the total muscarinic receptor levels [9,10]. 

Gylys KH, Fein JA, Yang F, Cole CM. 2004. Enrichment of presynaptic and postsynaptic markers by size-based gating analysis of synaptosome preparations from rat and human... 

There is now good evidence for a role of presynaptic neuropeptide Y receptors in disease states. As to the cardiovascular system, plasma neuropeptide Y levels are slightly increased in hypertensive patients and to a greater extent in cardiac failure (Morris 2004). An increase in neuropeptide Y levels is even an important prognostic marker for cardiovascular death in hemodialysis patients (Odar-Cederlof et al. 

The neuronal dopamine transporter (DAT) is a presynaptically located protein responsible for reuptake and thus removal of dopamine from the synaptic cleft. Dopamine transport carriers provide one of the most important means by which the actions of synaptic (and extrasynaptic) dopamine are terminated in the brain. As the DAT is exclusively located on terminals of dopamine neurons (reviewed in Boja et al., 1994), this transporter has served as a good anatomical dopaminergic marker. 

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