Protein cargo of Nef-containing exosomal extracellular vesicles may predict HIV-associated Neurocognitive Impairment status.

Exosomal extracellular vesicles (xEVs) in plasma and cerebrospinal fluid (CSF) of aviremic people living with HIV/AIDS (PLWHA) contain the HIV Negative factor (Nef) protein. However, the role of xEVs and Nef-containing-xEVs(xEV-Nef) in HIV-associated neuropathology is unknown. Here we performed a cross-sectional analysis of the content of xEVs derived from matched serum and CSF samples of PLWHAs diagnosed with either asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD).

Tibolone facilitates lordosis behavior through estrogen, progestin, and GnRH-1 receptors in estrogen-primed rats.

A dose-response study was made of the broad-spectrum gonadal steroid agonist tibolone (TBL) on lordosis behavior in estradiol benzoate (EB: 5 µg) primed rats. Doses of TBL (0, 1, 4, and 16 μg) were infused to the right lateral ventricle 2 h before testing. The highest dose increased lordosis quotients significantly at 240 min and 360 min following infusion.

Protein kinase inhibitors infused intraventricularly or into the ventromedial hypothalamus block short latency facilitation of lordosis by oestradiol.

An injection of unesterified oestradiol (E ) facilitates receptive behaviour in E benzoate (EB)-primed, ovariectomised female rats when it is administered i.c.v.

Estrogen receptor α and β are involved in the activation of lordosis behavior in estradiol-primed rats.

The present study was designed to assess the participation of estrogen receptors alpha (ERα) and beta (ERβ) in the short-term facilitation of lordosis behavior in ovariectomized (ovx), estradiol (E) primed rats. In experiment 1, dose response curves for PPT and DPN (ERα and ERβ agonists, respectively) facilitation of lordosis behavior (lordosis quotient and lordosis score) were established by infusing these agonists into the right lateral ventricle (icv) in female rats injected 40h previously with 5μg of E benzoate. PPT doses of 0.

The importance of the chemical structure of pregnanes in the concurrent inhibition of estrous behavior in the female rat.

An investigation of aspects ranging from behavior to molecular electronic structure and physicochemical properties was performed to explore the role of 5α-pregnanedione (5α-DHP), 5β-pregnanedione (5β-DHP) and their precursor progesterone (P) on the concurrent inhibition of the sexual lordosis response in female rats. The concurrent inhibition of lordosis behavior occurs when ovariectomized rodents are primed simultaneously with estradiol (E2) and P. Thus, a second administration of P 40h later fails to induce the expected sexual response that takes place when E2 and P are administered sequentially 40h apart.

Sexual receptivity facilitated by unesterified estradiol: Dependence on estrogen and progestin receptors and priming dose of estradiol benzoate.

In some conditions, female sexual behavior in ovariectomized rats can be induced by continuous exposure of estradiol (E2) alone or by a single injection of a high dose of the long-lasting, esterified estradiol benzoate (EB). However, there are inconsistencies in the literature on the role of estrogens during priming or in the facilitation on female sexual behavior in EB-primed rats, as well as the cellular mechanisms involved. Either subcutaneous (sc) or intracerebral (icv) administration of some doses of free unesterified E2, induced lordosis in EB-primed rats.

Lordosis facilitation by leptin in ovariectomized, estrogen-primed rats requires simultaneous or sequential activation of several protein kinase pathways.

The present study tested the hypothesis that the Janus kinase 2, Src tyrosine kinases, and mitogen-activated protein kinase interact to regulate lordosis behavior induced by leptin in ovariectomized, estrogen-primed rats. The role of protein kinase A and protein kinase C in lordosis facilitation by leptin was also assessed. In experiment 1, the intracerebroventricular administration of leptin to ovariectomized, estradiol-primed rats significantly stimulated lordosis behavior at 1, 2 and 4 h post-injection tests.

Src kinase signaling mediates estrous behavior induced by 5β-reduced progestins, GnRH, prostaglandin E2 and vaginocervical stimulation in estrogen-primed rats.

The progesterone receptor (PR) is a dual function protein that acts in the nucleus as a transcriptional factor and at the cytoplasm as a scaffold for the Src-MAPK signaling pathway. Several agents lacking affinity for the PR, such as 5β-reduced progestins, GnRH or prostaglandin E(2) (PGE(2)) facilitate estrous behavior in ovariectomized (ovx), estrogen-primed rats yet their action is blocked by the antiprogestin RU486. We hypothesize that these agents act by using the PR-Src-mitogen activated protein kinase alternative pathway.

The nitric oxide pathway participates in lordosis behavior induced by central administration of leptin.

Intracerebroventricular (icv) administration of leptin facilitates lordosis behavior in ad libitum-fed, estrogen-primed rats. The cellular mechanism involved in this response is unknown. The present study tested the hypothesis that the nitric oxide-guanylyl cyclase, cGMP-dependent protein kinase (PKG) pathway is involved in the facilitation of lordosis behavior induced by the central administration of leptin.

Leptin facilitates lordosis behavior through GnRH-1 and progestin receptors in estrogen-primed rats.

Dose response curves for leptin facilitation of estrous behavior (lordosis and proceptivity) were made by infusing the peptide into the lateral ventricle (icv) of ovariectomized (ovx), ad libitum-fed rats injected 40h previously with 5μg of estradiol benzoate. Leptin doses of 1 and 3μg produced significant lordosis quotient at 60min post-injection, with maximal lordosis being displayed at 120min. Yet the intensity of lordosis was weak, and a high incidence of rejection behaviors was found.

A role for Src kinase in progestin facilitation of estrous behavior in estradiol-primed female rats.

This study tested the hypothesis that the Src/Raf/MAPK signaling pathway is involved in the facilitation of the lordosis and proceptive behaviors induced by progesterone (P) and its ring A-reduced metabolites in ovariectomized, estradiol-primed rats. Intraventricular (icv) infusion of PP2 (7.5, 15 and 30 microg), a Src kinase inhibitor, significantly depressed P-dependent estrous behavior (lordosis and proceptivity) in estradiol-primed rats.

Role of progesterone receptor isoforms in female sexual behavior induced by progestins in rats.

Progesterone and its ring A reduced metabolites regulate female sexual behavior through the direct or indirect activation of progesterone receptor (PR) which has two isoforms with different function and regulation: PR-A and PR-B. The contribution of each PR isoform to the regulation of lordosis in rats is unknown. We explored the role of PR isoforms in lordosis display induced by progesterone and two of its ring A reduced metabolites: 5alpha-pregnan-3,20-dione (5alpha-DHP), and 5beta,3beta-pregnan-20-one (5beta,3beta-Pgl) in adult ovariectomized rats.

Nitric oxide and ERK/MAPK mediation of estrous behavior induced by GnRH, PGE2 and db-cAMP in rats.

We tested the hypothesis that GnRH, PGE2 and db-cAMP act via the nitric oxide (NO)-cGMP and MAPK pathways to facilitate estrous behavior (lordosis and proceptivity) in estradiol-primed female rats. Estradiol-primed rats received intracerebroventricular (icv) infusions of pharmacological antagonists of NO synthase (L-NAME), NO-dependent soluble guanylyl cyclase (ODQ), protein kinase G (KT5823), or the ERK1/2 inhibitor PD98059 15 min before icv administration of 50 ng of GnRH, 1 microg of PGE2 or 1 microg of db-cAMP. Icv infusions of GnRH, PGE2 and db-cAMP enhanced estrous behavior at 1 and 2 h after drug administration.

GnRH mediates estrous behavior induced by ring A reduced progestins and vaginocervical stimulation.

The present study was designed to assess the participation of gonadotropin-releasing hormone (GnRH) in the display of estrous behavior induced by application of vaginal-cervical stimulation (VCS) and by the intracerebroventricular (icv) administration of progesterone and its ring A-reduced metabolites to ovariectomized (ovx), estradiol benzoate (E2B) primed rats. Icv injection of Antide, a GnRH-1 receptor antagonist, significantly depressed lordosis behavior in ovx, E2B-primed rats treated with icv GnRH. Application of VCS to ovx, E2B-primed rats facilitated both lordosis and proceptivity.

Lordosis facilitation by LHRH, PGE2 or db-cAMP requires activation of the kinase A signaling pathway in estrogen primed rats.

Dose-response curves for lordosis and proceptive behaviors were obtained for luteinizing hormone releasing hormone (LHRH), prostaglandin E2 (PGE2) and dibutyryl cyclic AMP (db-cAMP), by infusing them in the right lateral ventricle (i.c.v.

Facilitation of estrous behavior by vaginal cervical stimulation in female rats involves alpha1-adrenergic receptor activation of the nitric oxide pathway.

In estrogen-primed female rats, vaginal cervical stimulation (VCS) provided by male intromissions or by an experimenter enhances estrous behaviors exhibited by females during subsequent mating with a male. We tested the hypothesis that alpha(1)-adrenergic receptors, acting via the nitric oxide-cGMP-protein kinase G pathway, mediate VCS-induced facilitation of female reproductive behaviors. Ovariectomized, estradiol-primed rats received intracerebroventricular (icv) infusions of vehicle or pharmacological antagonists 15 or 60min before VCS.

Differential effect of kinase A and C blockers on lordosis facilitation by progesterone and its metabolites in ovariectomized estrogen-primed rats.

Dose response curves for lordosis behavior was obtained for progesterone (P) and its two ring A-reduced metabolites: 5alpha-pregnanedione (alpha-DHP) and 5alpha,3alpha-pregnanolone (5alpha,3alpha-Pgl) by infusing these progestins in the right lateral ventricle (rlv) of ovariectomized (ovx) estradiol-treated rats (2 microg estradiol benzoate; EB), 40 h before intracerebro-ventricular (icv) injection. Effective doses 50 (ED50) revealed that ring A-reduced progestins were more potent than P itself to induce lordosis behavior. Two dose levels, one producing the maximal effect and the other one producing a submaximal response (ED50-ED60), were selected for testing the capacity of RpAMPS, a kinase A blocker, and H7, a kinase C blocker, to modify the response to the three progestins.

Estradiol and testosterone modulate the anesthetic action of the GABA-A agonist THIP, but not of the neurosteroid 3alpha,5beta-pregnanolone in the rat.

Rationale: As sex steroids modify the number and distribution of brain gamma-aminobutyric acid (GABA)A receptor subunits, we investigated the potential modulation of anesthesia, induced by agents acting on the GABAA receptor, by estrogen and androgen.

Objectives: To assess possible effects of sex and hormonal condition (i.e.