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Comparative Study 2002; 23(4): 345-350 PubMed PMID: 12195239 Citation  Keywords:  Aging:metabolism, Animals, Antioxidants:metabolism, Darkness, Hippocampus:enzymology, Lighting, Lipid Peroxidation:physiology, Male, Pineal Gland:physiology, Rats, Rats, Wistar, Receptors, N-Methyl-D-Aspartate:metabolism, Superoxide Dismutase:metabolism,.   

OBJECTIVES: To investigate the effects of pinealectomy on lipid peroxidation, antioxidant status and NMDA receptor subunits 2A and 2B concentrations in hippocampus.

DESIGN: Forty-eight male Wistar-albino rats were used.

SETTINGS: Animals were divided into three groups: 24 h dark throughout the study (highest melatonin release), 24 h light exposure (light-induced functional pinealectomy) and 12 h light/12 h dark exposure (control group). Thereafter, each group was divided into two groups as young and old animals.

RESULTS: There was an increase in NR2A and NR2B concentration in DY group compared to all other treatments. CuZn and Mn SOD activities were found to be increased in CO compared to CY group. Continual light exposure for 4 weeks did not change neural CuZn and Mn SOD activities. In old rats, light exposure reduced the activities of both CuZn and Mn SOD relative to those in the young animals. In addition, CuZn and Mn SOD activities were higher in dark exposed rats than in those in the continual light exposed or LD 12:12 rats. GSH-Px activity was found elevated in the DY rats compared to the CY groups. MDA levels were significantly higher in the CO than in the CY group.

CONCLUSIONS: NR2A and NR2B receptor concentrations in hippocampus of the rats maintained in dark showed significant increases compared to the control and functional pinealectomy groups but there was no significant increase in lipid peroxidation....

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Journal Article 2002; 23(4): 315-320 PubMed PMID: 12195233 Citation  Keywords:  Animals, Genes, Immediate-Early:physiology, Hypothalamus:cytology, Male, Neurons:physiology, Physical Stimulation, Proto-Oncogene Proteins c-fos:genetics, Rats, Rats, Sprague-Dawley, Skin:radiation effects,.   

OBJECTIVES: The purpose of this study was to determine: 1) The spatial pattern of c-fos gene expression in rat hypothalamic neurons after exposure to NMS and 2) The expression of c-fos gene after combined exposure to NMS and EHF irradiation of the rat skin.

METHODS: The experiments were performed on 28 male adult Sprague-Dawley rats. After rats were subjected to noxious mechanical stimulation (NMS) or its combination with EHF irradiation of the skin, cells in various hypothalamic structures were analyzed to determine theirs effects on c-fos gene expression, an accepted marker of the activation of neurons. C-Fos-like protein was revealed by an indirect immunoperoxidase method.

RESULTS: This study revealed that NMS stimulates c-fos gene expression in the anterior hypothalamic nucleus (AHN), dorsomedial hypothalamic nucleus (DMH), ventromedial hypothalamic nucleus (VMH), and lateral hypothalamic area (LHA) by 157, 101, 199 and 115% respectively compared to control animals. Combined exposure to NMS and EHF irradiation directed at the skin in the region of the St36 acupuncture point projection site (left side) results in a decrease of the number of neurons that are activated in the AHN, DMH, VMH, and LHA by 33.6, 13.2, 31.0 and 32.9% respectively compared to the number of neurons activated by exposure to NMS by itself. EHF exposure of the skin of rats not subjected to NMS differentially effects the number of c-Fos positive cells expressed in hypothalamic structures: a decrease of 39.7% was observed in the number of activated neurons in the central part of LHA (level 28) compared to sham-irradiated animals, while an increase of 80.95% was noted in the number of c-Fos positive cells in the DMH compared to sham-irradiated animals.

CONCLUSIONS: The spatial pattern and degree of activation of c-fos gene expression has been shown in cells of the hypothalamus of rats after exposure to NMS by itself and after NMS combined with EHF irradiation of the skin. The "stress" reaction of cells in specific hypothalamic structures has been shown to be decreased after EHF exposure of the skin....

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Comparative Study 2002; 23(3): 249-254 PubMed PMID: 12080287 Citation  Keywords:  Animals, Body Temperature, Brain Ischemia:pathology, Infarction, Middle Cerebral Artery:drug therapy, Male, Neuropeptides:pharmacology, Neuroprotective Agents:pharmacology, Pituitary Adenylate Cyclase-Activating Polypeptide, Rats, Rats, Wistar, Vasoactive.   

OBJECTIVES: Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) belong to the same peptide family, and both neuropeptides have been shown to exert in vitro and in vivo neurotrophic and neuroprotective effects. The aim of the present study was to investigate and compare the protective effects of PACAP and VIP in permanent focal cerebral ischemia in rats. The effect on the progression of the cerebral infarct was also studied.

METHOD: Male rats were injected 450 pmol PACAP or VIP dissolved in physiological saline intracerebroventricularly, preceding the occlusion of the middle cerebral artery. Control animals received vehicle treatment. Permanent focal ischemia was induced by the intraluminal filament occlusion of the middle cerebral artery. Animals were sacrificed 12 or 24 hours after the onset of ischemia, and infarcted brain areas were determined by staining bran sections with triphenyl-tetrazolium chloride.

RESULTS: Twelve hours after ischemia, the infarcted brain volume resulted to be 14.8% in the control group, 15.3% in the VIP-treated group and 5.8% in the PACAP-treated animals. Twenty-four hours after middle cerebral artery occlusion, the infarcted brain volumes were 21.5%, 20.7% and 14.3% in the control, VIP and PACAP-treated animals, respectively.

CONCLUSION: Our results provide further evidence for the neuroprotective effects of PACAP38 as given in form of a preischemic bolus. It slows down the progression of the evolution of the infarct and reduces the final infarct size. In contrast, a related peptide, VIP, does not have neuroprotective effects under the same experimental conditions....

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Journal Article 2002; 23(3): 231-237 PubMed PMID: 12080284 Citation  Keywords:  Altitude, Animals, Animals, Newborn, Hypoxia:pathology, Male, Mitochondria:physiology, Organ Size, Rats, Rats, Wistar, Testis:chemistry, Testosterone:analysis,.   

OBJECTIVE: To investigate the effects of continued hypoxia on postnatal development of the rat testis.

DESIGN: Wistar rats were exposed to simulated hypoxia from birth to postnatal day (PND) 45. Testosterone (T) in the plasma and the testis was measured in rats at PND 3, 7, 14, 21, 28, 35 and 45 respectively. Testis histology and cellular ultrastructure were studied.

RESULTS: a) Hypoxia induced a significant arrest of testes weight gain after PND 28; b) T release was significantly attenuated after PND 21; c) Alterations in histology and cellular ultrastructure were found in the testis, showing the swelling of testis interstitium and the enlargement of mitochondria in Leydig cells.

CONCLUSION: Postnatal hypoxia stress alters testis development both in terms of function and structure, especially at the critical age of gonadal development....

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Journal Article 2002; 23(Suppl 1): 104-109 PubMed PMID: 12019362 Citation  Keywords:  Alkaline Phosphatase:metabolism, Animals, Biomarkers, Bone and Bones:metabolism, Collagen:metabolism, Female, Melatonin:pharmacology, Osteoporosis:metabolism, Ovariectomy, Pineal Gland:physiology, Rats, Rats, Wistar,.   

BACKGROUND AND OBJECTIVES: There have been suggestions in literature that characteristic changes of bone mass in osteoporosis may be related to the melatonin (Mel): The aim of this study was to demonstrate whether pinealectomy and Mel administration can affect postmenopausal osteoporosis processes induced in female rats by way of ovariectomy.

METHODS: The study included 198 animals; 6 remained intact (0), 96 were ovariectomized (Ox), and the remaining ones underwent a sham operation (SOx). Two weeks after surgery, the rats were divided into eight groups: 1) SOx + SPx, 2) SOx + SPx + Mel, 3) Ox + SPx, 4) Ox + SPx + Mel, 5) SOx + Px, 6) SOx + Px + Mel, 7) Ox + Px, 8) Ox + Px + Mel. Animals from the 5th, 6th, 7th and 8th groups were pinealectomized (Px) while the remaining ones underwent a sham operation (SPx). Two weeks after surgery Mel (50microg/100g of bm) were administered intraperitoneally in rats in the 2nd, 4th, 6th and 8th groups while the remaining animals were administered with solvent only (5% solution of ethyl alcohol in physiological saline). Rats were administered the Mel solution or the solvent daily between 5 and 6 pm during a 4-week period. At the appropriate time, i.e. prior to surgery (group 0) and after 6, 12, 18 and 24 weeks from Px or SPx (time subgroups a, b, c and d) the animals were placed separately in metabolic cages (from 6.30 until 9.30 am) in order to collect urine aliquots for HYP and Ca determinations. The blood for the assay of ALP, PICP and ICTP was collected within the next 24 hours at 8 am (rats killed by decapitation).

RESULTS: The study has shown that pinealectomy had inducing, while exogenous Mel suppressing effect upon the level of investigated markers of bone metabolism; these changes were more pronounced in ovariectomized rats. Administration of Mel only partially levelled changes of bone metabolism caused by pinealectomy. In rats with preserved pineal gland effect of Mel on bone turnover markers was less pronounced. After discontinuing administration of Mel distinct tendency to increase studied biochemical markers of bone metabolism was shown.

CONCLUSION: Our findings suggest that Mel is an important modulator of experimental osteoporosis processes induced in female rats by way of ovariectomy....

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Journal Article 2002; 23(2): 149-154 PubMed PMID: 12011801 Citation  Keywords:  Animals, Cells, Cultured, Enzyme Inhibitors:pharmacology, Female, Follicle Stimulating Hormone:blood, Leptin:pharmacology, Luteinizing Hormone:blood, Neuropeptide Y:pharmacology, Nitric Oxide:metabolism, Pituitary Gland:cytology, Rats, Rats, Inbred WKY, o.   

OBJECTIVES: The aim of this study was to investigate the influence of NMMA on the mechanism of leptin and NPY action in in vivo and in vitro on pituitary hormone release by female rats in diestrus.

METHODS: In vivo experiments based on four-day ip injections of: 1) murine recombinant leptin (mrLep); 2) human NPY; 3) saline; 4) NMMA (50 microg) was applied prior to administration of mrLep; 5) NMMA (50 microg) was applied prior to administration of NPY; 6) NMMA (50 microg); 7) NMMA (350 microg) was applied prior to administration of mrLep; 8) NMMA (350 microg). The blood samples for LH and FSH were collected after decapitation of animals on the fifth day of study. In vitro experiments studied the effects of these peptides on LH release from pituitary cell culture.

RESULTS: In vivo: Leptin+ NMMA (50 microg) stimulated LH. NPY+ NMMA (50 microg) increased LH. NMMA (350 microg) stimulated FSH release. In vitro: The stimulatory effect of leptin on LH release in vitro was observed after 120 min of incubation, but after 60 mins of incubation the inhibitory effect of leptin on LH release was increased by NMMA. Leptin +NMMA (vs NMMA) decreased LH release with highest statistical significance. NPY 10 nM 60 min after incubation decreased LH release. There was no effect of NMMA on LH release.

CONCLUSION: In vivo results show, that NO probably mediates in leptin action on LH release. Moreover, effects of leptin on LH release from cultured pituitary cells are dependent on time of incubation. NPY decreased LH release in vitro....

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Journal Article 2002; 23(2): 101-104 PubMed PMID: 12011793 Citation  Keywords:  Animals, Enzyme Activation:drug effects, Gonadal Steroid Hormones:pharmacology, Gonadotropin-Releasing Hormone:metabolism, Male, Nitric Oxide:metabolism, Nitric Oxide Synthase:metabolism, Preoptic Area:drug effects, Rats, Sexual Maturation:physiology, Tes.   

OBJECTIVES: To determine the effect of testosterone administration to prepubertal (15 days old) and peripubertal rats (30 days old) on hypothalamic nitric oxide synthetase (NOS), and GnRH release.

METHODS: Hypothalamic samples containing the anterior preoptic and medial basal areas (APO-MBH) were incubated for 30 minutes in 500 l of Earle's medium with glucose (1 mg/ml) and bacitracin (20 mM). GnRH was determined by RIA in the medium and NOS activity was determined in APO-MBH after 10 min of incubation by the conversion of (14) C arginine to (14) C citrulline.

RESULTS: Treatment with testosterone propionate, significantly decreased NOS hypothalamic activity in prepubertal male rats. (

CONTROL: 58.41 +/- 0.85; Testosterone: 25.61 +/- 1.40, p<0.001) and had no effect in peripubertal male rats (CONTROL 49.28 +/- 1.50; Testosterone 51.48 +/- 5.2 pmoles NO/10 min/hypothalamus). On the other hand, in prepubertal rats the treatment decreased Gn-RH release (

CONTROL: 3.62 +/- 0.23; Testosterone: 1.38 +/- 0.11 (pg/ml medium, p<0.001) and had no effect on Gn-RH release in 30 days old rats (

CONTROL: 3.65 +/- 0.33;Testosterone: 4.15 +/- 0.36 pg/ ml, medium).

CONCLUSION: These results clearly demonstrated that testosterone has an inhibitory effect on hypothalamic NOS activity in prepubertal rats while it did not affect the concentration of this neurotransmitter system in peripubertal rats. This pattern is similar to that observed with GnRH hypothalamic release since testosterone has an inhibitory effect in prepubertal rats and did not modify the GnRH release in peripubertal rats. Taking into account the well known stimulatory effect of NO on GnRH and the decrease in the sensitivity of GnRH-gonadotrophin axis to the inhibitory feedback effect of testosterone during sexual maturation and the onset of puberty, it is proposed that the changes here described are connected with maturational modifications in the sexual hormones on-GnRH axis connected with the onset of puberty....

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Journal Article 2002; 23(1): 49-53 PubMed PMID: 11880862 Citation  Keywords:  Aging:physiology, Animals, Circadian Rhythm, Freund's Adjuvant:administration & dosage, Hydroxyindoleacetic Acid:metabolism, Injections, Subcutaneous, Male, Melatonin:metabolism, Norepinephrine:metabolism, Pineal Gland:metabolism, Rats, Rats, Wistar, Sero.   

OBJECTIVES: This study was performed to search for changes in rat pineal function attributed to age and immunization with Freund's adjuvant.

METHODS: Young (2 months) and old (18-20 months) Wistar rats were injected s.c. with Freund's adjuvant or its vehicle. Eighteen days later, at the acute phase of arthritis, pineal concentration of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) and melatonin was measured by high pressure liquid chromatography at 4 different time intervals throughout the nocturnal activity span.

RESULTS: Old rats had the lowest pineal 5-HT and 5-HIAA content, the decrease in 5-HIAA exceeding that of 5-HT; consequently, old rats had the lowest 5-HIAA/5-HT ratio, an index of pineal 5-HT turnover. Although immunization did not affect globally pineal 5-HT or 5-HIAA levels, significant interactions "immunization x age" and "immunization x time" were found, i.e., immunization augmented pineal 5-HT content at the beginning of the activity span in young rats and at second half of the activity span in young and old rats, and increased pineal 5-HIAA concentration in young rats at the second part of the activity span only. Freund's adjuvant treatment increased pineal 5-HT turnover exclusively in old rats, an effect mainly seen during the second part of the activity span. Old rats exhibited the lowest pineal NE and melatonin levels, immunization further depressing them.

CONCLUSION: The effect of immunization with Freund's adjuvant on a number of pineal pre- and postsynaptic parameters are age-dependent....

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