Signaling Role of Prokineticin 2 on the Estrous Cycle of Female Mice

The possible signaling role of prokineticin 2 (PK2) and its receptor, prokineticin receptor 2 (PKR2), on female reproduction was investigated. First, the expression of PKR2 and its co-localization with estrogen receptor (ERα) in the hypothalamus was examined. Sexually dimorphic expression of PKR2 in the preoptic area of the hypothalamus was observed. Compared to the male mice, there was more widespread PKR2 expression in the preoptic area of the hypothalamus in the female mice. The likely co-expression of PKR2 and ERα in the preoptic area of the hypothalamus was observed. The estrous cycles in female PK2-null, and PKR2-null heterozygous mice, as well as in PK2-null and PKR2-null compound heterozygous mice were examined. Loss of one copy of PK2 or PKR2 gene caused elongated and irregular estrous cycle in the female mice. The alterations in the estrous cycle were more pronounced in PK2-null and PKR2-null compound heterozygous mice. Consistent with these observations, administration of a small molecule PK2 receptor antagonist led to temporary blocking of estrous cycle at the proestrous phase in female mice. The administration of PKR2 antagonist was found to blunt the circulating LH levels. Taken together, these studies indicate PK2 signaling is required for the maintenance of normal female estrous cycles

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

PKR2 antagonist reduced plasma LH levels (Mean ± S.E.).

<p>The LH levels in the PKR2 antagonist (10 mg/kg 3Cl-MPL) group were significantly reduced compared to the vehicle treatment (n = 6 for each group, p<0.01.</p

Potency of PKR2 antagonist, 3Cl-MPL, in antagonizing PKR2.

<p>Antagonist potency was examined in Chinese Hamster Ovary (CHO) cells that stably express PKR2. RLU is an index for calcium influx measurement with a luminescence-based assay. The IC50 of 3Cl-MPL for PKR2 were 24.9±4.3 nM(Mean ± S.E.). Shown was representative of three independent experiments.</p

Abnormality of estrous cycle in PK2, PKR2 single and compound heterozygotic female mice.

<p>Three female mice in wild-type group, six female mice in each three mutant groups were studied. Panel A shows that three mutant groups exhibited irregular and longer estrous cycles compared to the wild-type control. PKR2 heterozygotes and the compound heterozygous female mice exhibited more pronounced abnormality. Panel B shows the quantification of estrous cycle lengths (Mean ± S.E.), * p<0.05 ** p<0.01. Panel C shows the percentage of days at each stage in 20 days of observance. D: diestrus, M: metestrus, E: estrus, P: proestrus.</p

Blocking of estrous cycle by PKR2 antagonist treatment.

<p>The administration of 3Cl-MPL (shown in red arrows) prevented the progression to estrous stage. Vehicle treatment was shown by blue arrows. E: estrus, P: proestrus, D: diestrus, M: metestrus.</p

The coexpression of PKR2 and ERα in the preoptic area. PKR2 and ERα were detected by immunofluorescence staining.

<p>PKR2-GFP expression was shown in green and ERα expression was shown in red. Yellow or orange color in the MnPO and AVPV regions indicates likely co-expression of PKR2 and ERα (scale bars:100 μm).</p

Neural compensation in older people with brain amyloid-β deposition

Recruitment of extra neural resources may allow people to maintain normal cognition despite amyloid-β (Aβ) plaques. Previous fMRI studies have reported such hyperactivation, but it is unclear whether increases represent compensation or aberrant overexcitation. We found that older adults with Aβ deposition had reduced deactivations in task-negative regions, but increased activation in task-positive regions related to more detailed memory encoding. The association between higher activity and more detailed memories suggests that Aβ-related hyperactivation is compensatory