INFLUENCE OF DIFFERENT LIGHTING REGIMEN ON THE MORPHOMETRIC CHARACTERISTICS OF NEURONS IN THE PARAVENTRICULAR NUCLEI OF THE RAT HYPOTHALAMUS

Paraventricular nuclei (PVN) of the hypothalamus are the autonomic center forcoordination of functions and consists of a number of neuronal populations - sub-nuclei,which differ in structural and functional features and the nature of nerve connectionswith various parts of the nervous and neuroendocrine systems. When studying stressreactions and actions of the stress-limiting factors, it is important to study subpopulationsof PVN neurons of the hypothalamus, synthesizing stress-releasing hormones, whichinitiate stress reactions of the body. One of the main factors that show a pronouncedeffect in the regulation of ACTH secretion is corticotropin-releasing factor (CRF). TheCRF-immunoreactive tracer was found mainly in the medial small-cell subnucleus of theparaventricular nuclei of the rat hypothalamus. Despite deep and comprehensive studiesof the hypothalamus, until now there are no unifed ideas about its individual reactivityand the degree of involvement of these structures into the stress reaction caused by theprolonged change in the lighting regime.Purpose - to fnd out the effect of different illumination regimes on the morphometriccharacteristics of the medial small-cell subnuclei of the paraventricular nuclei of thehypothalamus of mature and old rats.Material and methods. The experiments were conducted on 72 nonlinear white malerats, divided into 6 series of studies, in each of which the biomaterial sampling wascarried out at 14.00 and 02.00 h using morphometric and statistical research methods.Results. Morphometric assessment of the medial small-cell sub-nuclei of theparaventricular nuclei (msPVN) of the hypothalamus of rats revealed the diurnaldynamics of indices. It has been established that in both old and mature rats, theiraverage volume (p <0.05) signifcantly decreases at 2.00 compared to 14.00 undernormal lighting. The nuclear-cytoplasmatic ratio at 02.00 increases in comparison with14.00 respectively.When the animals were kept under constant illumination, more pronounced changesin the structures under study were established. In particular, the volume of neurons inthe msPVN of the hypothalamus decreases both mature and old rats compared withrats under standard illumination and even more in comparison with rats under lightdeprivation. In accordance with this, the NCR also changes. The average number ofneurons on the standard plane of the histological section also decreases in comparisonwith other illumination regimes. It is also necessary to point out that under conditionsof light stimulation in mature rats in msPVN, the average volume of neurons (p <0.05)noticeably decreases at 02:00 in comparison with 14:00, when the volume of theirnuclei does not change on average during the indicated study periods. This is reflected,respectively, in the NCR change, which increases at 02.00 in comparison with 14.00.As to the old rats, the average neuron volume does not decrease at 2.00 in comparisonwith 14.00 in msPVN neurons at light stimulation, as well as the volume of their neucleichanges, on average, is barely noticeable ,and according to it, NCR at 02.00 remainsstable in comparison with 14.00, and the average quantity of neurocytes in msPVN doesnot change on a standard plane of the histological section during various periods ofthe twenty four hours. At the same time, with various modifcations of the light regime,cytometric parameters of neurons under study in old rats, on average, are signifcantlylower (p <0.001) than those in mature rats.Conclusions. 1. The duration of the photoperiod signifcantly affects the 24 hoursactivity of msPVN in the hypothalamus of mature and old rats. In particular, in bothinvestigated groups of rats, the average volume of neurons (p <0.05) reliably decreasesat 2.00 under normal illumination in comparison with 14.00, and, accordingly, the NCR at 02.00 increases compared to 14.00. All cytometric parameters of their neurons in oldrats are, on average, signifcantly lower (p <0.001) than in mature rats.2. Constant illumination causes more pronounced changes in the morphometricparameters of the msPVN of the hypothalamus than light deprivation. Thus, in maturerats in the msPVN, the average volume of neurons (p <0.05) decreases noticeably at02:00 in comparison with 14:00, which is reflected, respectively, in the change in NCR,which increases at 02:00 compared to 14:00. For old rats, under light stimulation, allthe studied cytometric parameters of their neurons, on average, are signifcantly lower(p <0.001) than those in mature rats.

Relationship between Oxytocin and Osteoarthritis: Hope or Despair?

Oxytocin (OT) is involved in breastfeeding and childbirth and appears to play a role in regulating the bone matrix. OT is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and is released in response to numerous stimuli. It also appears to be produced by osteoblasts in the bone marrow, acting as a paracrine–autocrine regulator of bone formation. Osteoarthritis (OA) is a disease of the whole joint. Different tissues involved in OA express OT receptors (OTRs), such as chondrocytes and osteoblasts. This hormone, which levels are reduced in patients with OA, appears to have a stimulatory effect on chondrogenesis. OT involvement in bone biology could occur at both the osteoblast and chondrocyte levels. The relationships between metabolic syndrome, body weight, and OA are well documented, and the possible effects of OT on different parameters of metabolic syndrome, such as diabetes and body weight, are important. In addition, the effects of OT on adipokines and inflammation are also discussed, especially since recent data have shown that low-grade inflammation is also associated with OA. Furthermore, OT also appears to mediate endogenous analgesia in animal and human studies. These observations provide support for the possible interest of OT in OA and its potential therapeutic treatment.

Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats

Microbiota is involved in the host blood pressure (BP) regulation. The immunosuppressive drug mofetil mycophenolate (MMF) ameliorates hypertension. The present study analyzed whether MMF improves dysbiosis in mineralocorticoid-induced hypertension. Male Wistar rats were assigned to three groups: untreated (CTR), deoxycorticosterone acetate (DOCA)-salt, and DOCA treated with MMF for 4 weeks. MMF treatment reduced systolic BP, improved endothelial dysfunction, and reduced oxidative stress and inflammation in aorta. A clear separation in the gut bacterial community between CTR and DOCA groups was found, whereas the cluster belonging to DOCA-MMF group was found to be intermixed. No changes were found at the phylum level among all experimental groups. MMF restored the elevation in lactate-producing bacteria found in DOCA-salt joined to an increase in the acetate-producing bacteria. MMF restored the percentage of anaerobic bacteria in the DOCA-salt group to values similar to control rats. The improvement of gut dysbiosis was associated with an enhanced colonic integrity and a decreased sympathetic drive in the gut. MMF inhibited neuroinflammation in the paraventricular nuclei in the hypothalamus. This study demonstrates for the first time that MMF reduces gut dysbiosis in DOCA-salt hypertension models. This effect seems to be related to its capacity to improve gut integrity due to reduced sympathetic drive in the gut associated with reduced brain neuroinflammation.

The distribution of oxytocin and the oxytocin receptor in rat brain: relation to regions active in migraine

Background Recent work, both clinical and experimental, suggests that the hypothalamic hormone oxytocin (OT) and its receptor (OTR) may be involved in migraine pathophysiology. In order to better understand possible central actions of OT in migraine/headache pathogenesis, we mapped the distribution of OT and OTR in nerve cells and fibers in rat brain with a focus on areas related to migraine attacks and/or shown previously to contain calcitonin gene related peptide (CGRP), another neuropeptide involved in migraine. Methods Distribution of OT and OTR in the adult, rat brain was qualitatively examined with immunohistochemistry using a series of well characterized specific antibodies. Results As expected, OT was extensively localized in the cell somas of two hypothalamic nuclei, the supraoptic (SO or SON) and paraventricular nuclei (Pa or PVN). OT also was found in many other regions of the brain where it was localized mainly in nerve fibers. In contrast, OTR staining in the brain was mainly observed in cell somas with very little expression in fibers. The most distinct OTR expression was found in the hippocampus, the pons and the substantia nigra. In some regions of the brain (e.g. the amygdala and the hypothalamus), both OT and OTR were expressed (match). Mismatch between the peptide and its receptor was primarily observed in the cerebral and cerebellar cortex (OT expression) and hippocampus (OTR expression). Conclusions We compared OT/OTR distribution in the CNS with that of CGRP and identified regions related to migraine. In particular, regions suggested as “migraine generators”, showed correspondence among the three mappings. These findings suggest central OT pathways may contribute to the role of the hypothalamus in migraine attacks.

Muscarinic M2 receptor promotes vasopressin synthesis in mice supraoptic nuclei

Muscarinic acetylcholine receptors have been suggested to be implicated in arginine–vasopressin secretion because intracerebroventricular muscarinic agonist administration induces arginine–vasopressin release into the circulation. Although which subtype is involved in the regulation of arginine–vasopressin secretion is unclear, M2 receptors have been reported to be highly expressed in the hypothalamus. In the present study, M2 receptor-knockout mice were used to elucidate whether M2 receptor regulates arginine–vasopressin synthesis in the paraventricular nuclei and supraoptic nuclei of the hypothalamus. The number of arginine–vasopressin-immunoreactive neurons in M2 receptor-knockout mice was significantly decreased in the supraoptic nuclei, but not in the paraventricular nuclei compared with wild-type mice. Plasma arginine–vasopressin level in M2 receptor-knockout mice was also significantly lower than in the wild-type mice. Urinary volume and frequency as well as water intake in M2 receptor-knockout mice were significantly higher than those in wild-type mice. The V2 vasopressin receptor expression in kidneys of M2 receptor-knockout mice was comparable with that of wild-type mice, and increased urination in M2 receptor-knockout mice was significantly decreased by administration of desmopressin, a specific V2 receptor agonist, suggesting that V2 receptors in the kidneys of M2 receptor-knockout mice are intact. These results suggest that M2 receptors promote arginine–vasopressin synthesis in the supraoptic nuclei and play a role in the regulation and maintenance of body fluid.