Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Single-minded 1 (SIM1) mutations are one of the few known causes of nonsyndromic monogenic obesity in both humans and mice. Although the role of Sim1 in the formation of the hypothalamus has been described, its postdevelopmental, physiological functions have not been well established. Here we demonstrate that postnatal CNS deficiency of Sim1 is sufficient to cause hyperphagic obesity. We conditionally deleted Sim1 after birth using CaMKII-Cre (alpha-calcium/calmodulin-dependent protein kinase II-Cre) lines to recombine a floxed Sim1 allele. Conditional Sim1 heterozygotes phenocopied germ line Sim1 heterozygotes, displaying hyperphagic obesity and increased length. We also generated viable conditional Sim1 homozygotes, demonstrating that adult Sim1 expression is not essential for mouse or neuron survival and revealing a dosage-dependent effect of Sim1 on obesity. Using stereological cell counting, we showed that the phenotype of both germ line heterozygotes and conditional Sim1 homozygotes was not attributable to global hypocellularity of the paraventricular nucleus (PVN) of the hypothalamus. We also used retrograde tract tracing to demonstrate that the PVN of germ line heterozygous mice projects normally to the dorsal vagal complex and the median eminence. Finally, we showed that conditional Sim1 homozygotes and germ line Sim1 heterozygotes exhibit a remarkable decrease in hypothalamic oxytocin (Oxt) and PVN melanocortin 4 receptor (Mc4r) mRNA. These results demonstrate that the role of Sim1 in feeding regulation is not limited to formation of the PVN or its projections and that the hyperphagic obesity in Sim1-deficient mice may be attributable to changes in the leptin-melanocortin-oxytocin pathway.
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PMID:Postnatal Sim1 deficiency causes hyperphagic obesity and reduced Mc4r and oxytocin expression. 2022 15

The vasopressin 1b receptor (Avpr1b) is critical for social memory and social aggression in rodents, yet little is known about its specific roles in these behaviors. Some clues to Avpr1b function can be gained from its profile of expression in the brain, which is largely limited to the pyramidal neurons of the CA2 region of the hippocampus, and from experiments showing that inactivation of the gene or antagonism of the receptor leads to a reduction in social aggression. Here we show that partial replacement of the Avpr1b through lentiviral delivery into the dorsal CA2 region restored the probability of socially motivated attack behavior in total Avpr1b knockout mice, without altering anxiety-like behaviors. To further explore the role of the Avpr1b in this hippocampal region, we examined the effects of Avpr1b agonists on pyramidal neurons in mouse and rat hippocampal slices. We found that selective Avpr1b agonists induced significant potentiation of excitatory synaptic responses in CA2, but not in CA1 or in slices from Avpr1b knockout mice. In a way that is mechanistically very similar to synaptic potentiation induced by oxytocin, Avpr1b agonist-induced potentiation of CA2 synapses relies on NMDA (N-methyl-D-aspartic acid) receptor activation, calcium and calcium/calmodulin-dependent protein kinase II activity, but not on cAMP-dependent protein kinase activity or presynaptic mechanisms. Our data indicate that the hippocampal CA2 is important for attacking in response to a male intruder and that the Avpr1b, likely through its role in regulating CA2 synaptic plasticity, is a necessary mediator.
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PMID:Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2. 2486 46

Oxytocin (OXT) receptors (OXTRs) are prominently expressed in hippocampal CA2 and CA3 pyramidal neurons, but little is known about its physiological function. As the functional necessity of hippocampal CA2 for social memory processing, we tested whether CA2 OXTRs may contribute to long-term social recognition memory (SRM) formation. Here, we found that conditional deletion of Oxtr from forebrain (Oxtr-/-) or CA2/CA3a-restricted excitatory neurons in adult male mice impaired the persistence of long-term SRM but had no effect on sociability and preference for social novelty. Conditional deletion of CA2/CA3a Oxtr showed no changes in anxiety-like behavior assessed using the open-field, elevated plus maze and novelty-suppressed feeding tests. Application of a highly selective OXTR agonist [Thr4,Gly7]-OXT to hippocampal slices resulted in an acute and lasting potentiation of excitatory synaptic responses in CA2 pyramidal neurons that relied on N-methyl-d-aspartate receptor activation and calcium/calmodulin-dependent protein kinase II activity. In addition, Oxtr-/- mice displayed a defect in the induction of long-term potentiation, but not long-term depression, at the synapses between the entorhinal cortex and CA2 pyramidal neurons. Furthermore, Oxtr deletion led to a reduced complexity of basal dendritic arbors of CA2 pyramidal neurons, but caused no alteration in the density of apical dendritic spines. Considering that the methodologies we have used to delete Oxtr do not rule out targeting the neighboring CA3a region, these findings suggest that OXTR signaling in the CA2/CA3a is crucial for the persistence of long-term SRM.SIGNIFICANCE STATEMENT Oxytocin receptors (OXTRs) are abundantly expressed in hippocampal CA2 and CA3 regions, but there are little known about their physiological function. Taking advantage of the conditional Oxtr knock-out mice, the present study highlights the importance of OXTR signaling in the induction of long-term potentiation at the synapses between the entorhinal cortex and CA2 pyramidal neurons and the persistence of long-term social recognition memory. Thus, OXTRs in the CA2/CA3a may provide a new target for therapeutic approaches to the treatment of social cognition deficits, which are often observed in patients with neuropsychiatric disorders.
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PMID:Conditional Deletion of Hippocampal CA2/CA3a Oxytocin Receptors Impairs the Persistence of Long-Term Social Recognition Memory in Mice. 2927 8