Expansion and mechanistic insights into de novo DEAF1 variants in DEAF1-associated neurodevelopmental disorders.

De novo deleterious and heritable biallelic mutations in the DNA binding domain (DBD) of the transcription factor deformed epidermal autoregulatory factor 1 (DEAF1) result in a phenotypic spectrum of disorders termed DEAF1-associated neurodevelopmental disorders (DAND). RNA-sequencing using hippocampal RNA from mice with conditional deletion of Deaf1 in the central nervous system indicate that loss of Deaf1 activity results in the altered expression of genes involved in neuronal function, dendritic spine maintenance, development, and activity, with reduced dendritic spines in hippocampal regions. Since DEAF1 is not a dosage-sensitive gene, we assessed the dominant negative activity of previously identified de novo variants and a heritable recessive DEAF1 variant on selected DEAF1-regulated genes in 2 different cell models.

Regulation of cytokine-inducible SH2-containing protein (CIS) by ubiquitination and Elongin B/C interaction.

Cytokine-inducible SH2-containing protein (CIS) inhibits prolactin receptor (PRLR) signaling and acts as part of an E3 ubiquitin ligase complex through interactions with Elongin B/C proteins. This study aimed to identify CIS lysine ubiquitination sites and determine roles of ubiquitination and Elongin B/C interactions on CIS protein stability and PRLR signaling inhibition. Site-directed mutations revealed that CIS can be ubiquitinated on all six lysine residues.

Progesterone decreases tyrosine hydroxylase phosphorylation state and increases protein phosphatase 2A activity in the stalk-median eminence on proestrous afternoon.

The progesterone (P(4)) rise on proestrous afternoon is associated with dephosphorylation of tyrosine hydroxylase (TH) and reduced TH activity in the stalk-median eminence (SME), which contributes to the proestrous prolactin surge in rats. In the present study, we investigated the time course for P(4) effect on TH activity and phosphorylation state, as well as cAMP levels and protein phosphatase 2A (PP2A) activity and quantity, in the SME on proestrous morning and afternoon. P(4) (7.

Adenosine receptor antagonists and behavioral activation in NF-kappaB p50 subunit knockout mice.

Aims: Our previous work revealed that mice lacking the p50 subunit of transcription factor nuclear factor kappa B (NF-kappaB) (p50 KO mice) and genetically intact F2 mice have similar locomotion under basal conditions, yet p50 KO mice show greater locomotor activation after caffeine ingestion. In this report, we test whether KO mice display altered caffeine pharmacokinetics or increased caffeine-induced DA turnover relative to F2 mice, and evaluate the impact of intraperitoneal administration of specific adenosine and DA receptor antagonists on locomotor activity.

Main Methods: Concentrations of DA and caffeine were measured using high performance liquid chromatography.

Phosphorylation state of tyrosine hydroxylase in the stalk-median eminence is decreased by progesterone in cycling female rats.

Progesterone has the capacity to suppress hypothalamic dopaminergic neuronal activity on proestrous afternoon and prolong or amplify the preovulatory prolactin surge in rats. In the present study, we examined enzyme activity and phosphorylation state of tyrosine hydroxylase (TH) in the stalk-median eminence of cycling female rats on proestrus and estrus and related these to circulating progesterone levels. Phospho-TH levels were evaluated by Western blot analysis.

Estrogen genomic and membrane actions at an intersection.

Estradiol is a primary hormonal signal that synchronizes central neuronal activity changes during the female reproductive cycle. The cellular and molecular mechanisms for many of these changes are still not well understood. Exciting new findings of Roepke and colleagues indicate that estradiol regulates expression of key potassium channels as well as modulatory intracellular signaling molecules.

Prolactin modulates hypothalamic preproenkephalin, but not proopiomelanocortin, gene expression during lactation.

The aim of this study was to examine prolactin (PRL) regulation of preproenkephalin and proopiomelanocortin (POMC) gene expression in the hypothalamus during lactation. In the first experiment, lactating rats were deprived of pups for 3, 6, 12, or 24 h. Preproenkephalin mRNA levels were decreased in the arcuate nucleus (ARC) to 60 or 53% of suckled levels and in the ventromedial nucleus to 70% of suckled levels after 12 or 24 h but were unchanged in the striatum.

Progesterone induces dephosphorylation and inactivation of tyrosine hydroxylase in rat hypothalamic dopaminergic neurons.

After in vivo treatment, progesterone initially decreases tyrosine hydroxylase (TH) activity in the TIDA neurons, but subsequently increases TH activity with prolonged treatment. In order to explore the cellular mechanism for progesterone's effect, this study examined the acute inhibitory action of progesterone on TH activity in rat fetal hypothalamic dopaminergic neurons in vitro. Progesterone caused a rapid decrease in TH activity within 1 h, which was sustained for at least 6 h.