Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the pubertal period the mesocortical dopamine (DA) system undergoes substantial reorganization of neuronal connectivity and functional refinement. Netrins are guidance cues involved in the organization of neuronal circuitry. We have previously shown that adult mice that develop with reduced levels of the netrin-1 receptor [deleted in colorectal cancer (DCC)] display selective reorganization of mesocortical DA circuitry, show enhanced mesocortical DA function and exhibit a behavioural phenotype opposite to that observed in animal models of schizophrenia. Here we assess whether the dcc behavioural and DA phenotypes are present prior to the maturation of the mesocortical DA system by comparing dcc-heterozygous and wild-type mice at the post-weaning and peri-pubertal periods on various indices of DA function. At both the post-weaning and peri-pubertal ages, but unlike in adulthood, dcc-heterozygous and wild-type mice show no differences in the number of midbrain DA neurones or in tyrosine hydroxylase protein levels in the medial prefrontal cortex. Furthermore, the elevated baseline concentration of mesocortical DA and DA metabolites observed in adult dcc-heterozygous mice is not present in either post-weanling or peri-pubertal mice. Interestingly, post-weanling, but not peri-pubertal, dcc-heterozygous mice show greater baseline concentrations of DA metabolites in the nucleus accumbens, opposite to what was observed in adulthood. Finally, neither post-weanling nor peri-pubertal dcc-heterozygous mice demonstrate the blunted amphetamine-induced locomotor response observed in adulthood. Thus, these findings show that the 'protective' dcc phenotype has a post-pubertal emergence and indicate that DCC may play a role in the normal maturation of the mesocorticolimbic DA system.
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PMID:Post-pubertal emergence of a dopamine phenotype in netrin-1 receptor-deficient mice. 1978 79

We have shown previously that the netrin-1 receptor, unc-5 homologue C (UNC5C), is expressed by ventral tegmental area (VTA) dopamine (DA) neurons of rodents, but only from adolescence onwards (Manitt et al., 2010; Auger et al., 2013). The goal of this study was to characterize the expression of UNC5C by these neurons. Specifically, we assessed whether UNC5C expression is selective to DA neurons that project to the medial prefrontal cortex (mPFC), which undergo significant maturation during the adolescent period. To this end, we injected fluorescent retrograde tracer beads into the mPFC, nucleus accumbens (NAcc) core, or NAcc lateral shell of adult male wild-type C57Bl/6J mice and processed their brains for tyrosine hydroxylase (TH) and UNC5C immunofluorescence 2-3weeks later. VTA neurons with any combination of these immunolabels were visualized and counted using optical fractionator stereology. Our analysis revealed two main findings: (1) there are no differences in the proportions of UNC5C-positive DA neurons projecting to the mPFC, NAcc core, or NAcc lateral shell, and (2) the proportion of non-DA UNC5C-positive neurons targeting the mPFC is greater than the proportions of non-DA UNC5C-positive neurons targeting the NAcc core or lateral shell. These findings show that, contrary to our hypothesis, DA neurons projecting to the mPFC do not express UNC5C selectively. However, UNC5C expression by non-DA VTA neurons is predominantly found in those projecting to the mPFC and, as such, may play a role in their function.
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PMID:Target-dependent expression of the netrin-1 receptor, UNC5C, in projection neurons of the ventral tegmental area. 2433 68