Cerebral Cortex Of Male Rats Research Articles

Reduced ischemia‐reperfusion oxidative stress injury by melatonin and N‐acetylcysteine in the male rat brain

Middle cerebral artery occlusion (MCAO) is a model for inducing ischemic stroke in rodents, leading to devastating brain damage. Oxidative stress (OS) plays a crucial role in the pathogenesis of ischemia. In this study, the effect of melatonin and N-acetylcysteine on ischemia-reperfusion-induced oxidative stress injury in the cerebral cortex of male rats was investigated. 30 male Wistar rats were divided into sham, ischemic, NAC, melatonin and NAC + melatonin groups. All groups, except the sham group, underwent MCAO on the left side, and the treatment groups received intraperitoneal injections of either 50 mg/kg N-acetylcysteine (NAC) or 5 mg/kg melatonin or a combination of both 24 and 48 hours later. At 24 and 72 hours after surgery, the animals were examined for sensory and motor activity. The cerebral cortex was dissected after sacrificing the rats, infarct volume estimated and the concentrations of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nuclear factor erythroid-2 related factor 2 (Nrf2) were analyzed by enzyme-linked immunosorbent assay (ELISA). The results indicate that the NAC + melatonin group exhibited elevated sensory-motor activity and a reduced infarct volume rate in comparison to the ischemic group (p≤ 0.05). Compared to the ischemic group, the NAC + melatonin group showed a significant increase in SOD concentration and a significant decrease in MDA (p≤ 0.05). It can therefore be concluded that the simultaneous administration of NAC and melatonin can reduce the cerebral infarction volume, and improve neurological functions by modulating SOD and MDA.

INVESTIGATION OF GENE EXPRESSION LEVELS OF SOME PROTEINS RELATED TO THE PATHOGENESIS OF PARKINSON'S DISEASE IN RATS EXPOSED TO PRENATAL STRESS

INVESTIGATION OF GENE EXPRESSION LEVELS OF SOME PROTEINS RELATED TO THE PATHOGENESIS OF PARKINSON’S DISEASE IN RATS EXPOSED TO PRENATAL STRESS Ilayda VAROL1*, Sinem Ezgi TURUNC OZOGLU2 1 Department of Biochemistry, Faculty of Pharmacy, Izmir Katip Çelebi University, Izmir, Türkiye 2 Department of Biochemistry, Faculty of Pharmacy, Izmir Katip Çelebi University, Izmir, Türkiye ORCID Numbers: İlayda Varol: 0009-0000-4037-8612 Sinem Ezgi Turunc Ozoglu: 0000-0002-7587-7443 *Corresponding author: Ilayda VAROL Department of Biochemistry, Faculty of Pharmacy, Izmir Katip Çelebi University, Izmir, Türkiye E-mail: varolilayda@gmail.com Tel: +90 507 333 18 35 Ethical Committee Approval: The Ege University Ethics Committee on Animal Experiments approved this study (05/24/2017; Reference No. 2017-023). INVESTIGATION OF GENE EXPRESSION LEVELS OF SOME PROTEINS RELATED TO THE PATHOGENESIS OF PARKINSON’S DISEASE IN RATS EXPOSED TO PRENATAL STRESS Abstract This study was carried out in order to better understand how prenatal stress (PS) may affect the future onset of Parkinson's disease (PD). A dexamethasone-induced PS model was established in rats for the study. Changes in the expression levels of tyrosine hydroxylase (TH), α-synuclein (SNCA), dopamine transporter (SLC6A3), and parkin (PRKN) proteins, which play role in PD pathogenesis, were demonstrated by real-time PCR in the cerebral cortex of male rats exposed to PS. From GD 14 to 21, pregnant rats were injected daily with Dex or saline (100 μg/kg and 1 ml/kg). 3 months after birth, male rats underwent decapitation (n=5), cerebral cortex dissection was performed. Total RNA was isolated from cortexes and used for cDNA synthesis. Gene expression analyzes were performed according to the ∆∆CT method. The statistical differences between groups were analyzed by the Mann-Whitney test. Statistics were deemed significant at a level of 0.05. Dex exposure throughout pregnancy significantly increased mRNA levels of TH and SLC6A3. No significant differences were found in the mRNA levels of PRKN and SNCA between experimental groups. In conclusion, offspring exposed to PS may be more susceptible to PD in adulthood through changes in the cortical mRNA levels of TH and SLC6A3. Keywords: Prenatal stress, Parkinson’s Disease, Tyrosine hydroxylase, Dopamine transporter

Prenatal Dexamethasone Exposure in Male Rats Alters Gene Expression Patterns of Epigenetic Enzymes in Hippocampus and Cortex

Objective: This study aimed to examine the effects of prenatal stress (PS) induced by dexamethasone exposure on gene expression levels of epigenetic enzymes in hippocampus and cerebral cortex of male rats through relative mRNA levels of histone acetyltransferases (activating transcription factor 2, P300), histone deacetylases (HDAC1, HDAC2), and DNA methyltransferases (DNMT1, DNMT3a, DNMT3b). Methods: Pregnant rats were daily injected subcutaneously with dexamethasone (0.2 mg/kg) or saline during the third week of gestation. After birth, male rats were killed at 90 days of age (n = 5 for control and dexamethasone groups). Hippocampal and cortical tissues were used for gene expression analyses. The effects of dexamethasone on epigenetic mechanisms were investigated by real-time polymerase chain reaction through relative mRNA levels of DNMT1, DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2. Statistical comparisons were performed with Student’s t-test. Results: Prenatal dexamethasone exposure (PDE) caused increased DNMT1, DNMT3a, DNMT3b, activating transcription factor 2 and decreased P300 mRNA levels in hippocampus while increased DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2 mRNA levels were achieved in cortex. Furthermore, no significant differences were obtained in cortical DNMT1 and hippocampal HDAC1 and HDAC2 gene expression levels between control and prenatally stressed rats. Conclusion: Our results emphasize the effect of prenatal dexamethasone exposure on gene expression levels of epigenetic enzymes involved in histone acety latio n/dea cetyl ation and DNA methylation in male rats and suggest that prenatal stress may lead to epigenetic dysregulation through alterations in hippocampal and cortical gene expression patterns of DNMT1, DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2.

Neuroprotective effect of dietary black seed flour on key enzymes linked with neuronal signaling molecules in rats exposed to mixture of environmental metals

The study examined the neuroprotective effect of dietary black seed flour (D-BSF) in rats exposed to mixed-metals. Animals were divided into six groups (n = 8): normal control rats; normal rats treated with 10 and 20% black seed flour (D-BSF), respectively; intoxicated rat; intoxicated rats treated with 10 and 20% D-BSF, respectively for 14 days. Our results revealed that neuronal signaling molecules including acetylcholinesterase (AChE), butrylcholinesterase (BuChE), adenosine deaminase (ADA), monoamine oxidase-A (MAO-A) activities, and malonaldehyde (MDA) levels in cerebral cortex were significantly (p < .05) higher followed by alteration in the activity of econucleotidase using ATP, ADP, and AMP as substrates in rats exposed to mixed metals. Remarkably, D-BSF significantly (p < .05) inhibited the activities of AChE, BuChE, ADA, and MAO-A with corresponding wellness of the neuronal MDA contents. However, inhibition of AChE, BuChE, ADA, MAO-A, ectoenzymes activities suggests possible mechanisms by which D-BSF prevent mixed-metal toxicity in cerebral cortex of male rats. Practical application Nigella sativa (Black seed) is widely used in Asian traditional medicine and some part of Africa, as prevention against several diseases such as cough, inflammation and diabetes. Previous investigations have also shown that black seed oil could delay carcinogenic process, inhibit inflammation and interrupt oxidative damage in nephrons. It is also commonly consumed for its supposed multi-functioning ability and neuronal promoting effects. The results of this study revealed valuable evidence concerning the possible usage of D-BSF as natural, alternative and/or complementary supplement with neuroprotective potentials. Hence, this study underscores D-BSF as functional food against neurological disorders and suggests some possible mechanisms by which it prevents mixed-metal intoxication in cerebral cortex of male rats.

Neuroprotective potential of Citrullus lanatus seed extract and vitamin E against mercury chloride intoxication in the brain of male Wistar rat.

Mercury chloride toxicity continues to be relevant in the advent of increased interest in mining activity in Nigeria. The neuroprotective potential of Citrullus lanatus seed extract (CLSE) (Watermelon seed) and vitamin E (VIT E) on mercury chloride intoxication on the frontal cerebral cortex of male rats was investigated. Forty two (42) male rats were randomized into six groups of 7 rats each. Group 1: control group received food and water; Group 2: received CLSE (200 mg/kg); Group 3: received VIT E (500 mg/kg); Group 4: received HgCl2 (4 mg/kg); Group 5: received HgCl2 (4 mg/kg) + VIT E (500 mg/kg) and Group 6: received HgCl2 (4 mg/kg) + CLSE (200 mg/kg). Treatment lasted 14 days and on 15th day of the experiment, gross morphometric, behavioural tests and brain tissue processing using paraffin wax technique were done. While gross body and brain morphometric evaluations were not significantly different, behavioural studies show that CLSE and VIT E significantly (p<0.05) increased the number of lines crossed relative to control. Histology showed that HgCl2 caused degeneration of neurons of the frontal cerebral cortex when compared with the control. Co-treatment of HgCl2 with CLSE and VIT E showed histological features of protection of cerebral neurons from mercury damage. Concluding, CLSE and VIT E mitigated HgCl2–induced degeneration of frontal cerebral cortical neurons thus demonstrating their neuropotential capacity to protect cerebral cortex neurons from mercury toxicity.

Intracellular Progesterone Receptor Mediates the Increase in Glioblastoma Growth Induced by Progesterone in the Rat Brain

Progesterone (P) is a steroid hormone involved in the development of several types of cancer including astrocytomas, the most common and malignant brain tumors. We undertook this study to investigate the effects of P on the growth and infiltration of a tumor caused by the xenotransplant of U87cells derived from a human astrocytoma grade IV (glioblastoma) in the cerebral cortex of male rats and the participation of intracellular progesterone receptor (PR) on these effects. Eight weeks after the implantation of U87cells in the cerebral cortex, we administered phosphorothioated antisense oligodeoxynucleotides (ODNs) to silence the expression of PR. This treatment lasted 15days and was administered at the site of glioblastoma cells implantation using Alzet osmotic pumps. Vehicle (propylene glycol) or P4 (400μg/100g) was subcutaneously injected for 14days starting 1day after the beginning of ODN administration. We observed that P significantly increased glioblastoma tumor area and infiltration length as compared with vehicle, whereas PR antisense ODNs blocked these effects. P, through the interaction with PR, increases the area and infiltration of a brain tumor formed from the xenotransplant of human glioblastoma-derived U87cells in the cerebral cortex of the rat.

Age Increase of Estrogen Receptor-α (ERα) in Cortical Astrocytes Impairs Neurotrophic Support in Male and Female Rats

Rodent models show decreased neuronal responses to estradiol (E2) during aging (E2-desensitization) in association with reduced neuronal estrogen receptor (ER)-α, but little is known about age changes of E2-dependent astrocytic neurotrophic support. Because elevated expression of astrocyte glial fibrillary acidic protein (GFAP) is associated with impaired neurotrophic activity and because the GFAP promoter responds to ERα, we investigated the role of astrocytic ERα and ERβ in impaired astrocyte neurotrophic activity during aging. In vivo and in vitro, ERα was increased greater than 50% with age in astrocytes from the cerebral cortex of male rats (24 vs 3 months), whereas ERβ did not change. In astrocytes from 3-month-old males, experimentally increasing the ERα to ERβ ratio induced the aging phenotype of elevated GFAP and impaired E2-dependent neurite outgrowth. In 24-month-old male astrocytes, lowering ERα reversed the age elevation of GFAP and partially restored E2-dependent neurite outgrowth. Mixed glia (astrocytes to microglia, 3:1) of both sexes also showed these age changes. In a model of perimenopause, mixed glia from 9- to 15-month rats showed E2 desensitization: 9-month regular cyclers retained young-like ERα to ERβ ratios and neurotrophic activity, whereas 9-month noncyclers had elevated ERα and GFAP but low E2-dependent neurotrophic activity. In vivo, ERα levels in cortical astrocytes were also elevated. The persisting effects of ovarian acyclicity in vitro are hypothesized to arise from steroidal perturbations during ovarian senescence. These findings suggest that increased astrocyte ERα expression during aging contributes to the E2 desensitization of the neuronal responses in both sexes.

The potential role of ozone in ameliorating the age-related biochemical changes in male rat cerebral cortex

Controlled ozone (O(3)) administration is known to promote oxidative preconditioning and, thus, may reverse chronic oxidative stress that accompanies aging. Therefore, the present work was undertaken to study the potential role of O(3) in ameliorating certain age-related biochemical changes represented by impaired activities of inner mitochondrial membrane enzymes, compromised energy production and increased oxidative burden in male rat cerebral cortex. Prophylactic administration of O(3)-O(2) mixture to 3 month-old rats, at an intrarectal dose of 0.6 mg O(3) kg(-1) body weight twice/week for 3 months then once/week until the age of 15 months, normalized reduced glutathione content, adenosine triphosphate/adenosine diphosphate ratio, mitochondrial superoxide dismutase (SOD) and complex IV (cytochrome-c oxidase) activities, improved glutathione redox index (GSHRI), complex I (NADH-ubiquinone oxidoreductase) and mitochondrial nitric oxide synthase (mtNOS) activities, and attenuated the rise in malondialdehyde (MDA) and mitochondrial protein carbonyl levels. On the other hand, therapeutic administration of the same dose of O(3)-O(2) mixture to 14 month-old rats three times/week for 1 month, reduced mitochondrial protein carbonyl level only. Other favorable effects, including normalization of Na,K-adenosine triphosphatase (Na,K-ATPase) activity and reduction in lipofuscin level in the prophylactic group, as well as improvement in mitochondrial SOD and complex I activities with a decrease in total MDA level in the therapeutic group, were comparable to the effects observed in the corresponding O(2)-treated control groups. In conclusion, the present study revealed that prophylactic administration of O(3)-O(2) mixture provided better amelioration of age-related cerebrocortical alterations by combining the advantages of both O(3) and O(2) therapies.

Age-changes in gene expression in primary mixed glia cultures from young vs. old rat cerebral cortex are modified by interactions with neurons

Astrocytic GFAP expression increases during normal aging in many brain regions and in primary astrocyte cultures derived from aging rodent brains. As shown below, we unexpectedly found that the age-related increase of GFAP expression was suppressed in mixed glia (astrocytes+microglia). However, the age-related increase of GFAP was observed when E18 neurons were co-cultured with mixed glia. Thus, the presence of microglia can suppress the age-related increase of GFAP, in primary cultures of astrocytes. To more broadly characterize how aging and co-culture with neurons alters glial gene expression, we profiled gene expression in mixed glia from young (3 mo) and old (24 mo) male rat cerebral cortex by Affymetrix microarray (Rat230 2.0). The majority of age changes were independent of the presence of neurons. Overall, the expression of twofold more genes increased with age than decreased with age. The minority of age changes that were either suppressed or revealed by the presence of neurons may be useful to analyze glial-neuron interaction during aging. Some in vitro changes are shared with those of aging rat hippocampus in studies from the Landfield group (Rowe et al., 2007; Kadish et al., 2009).

Estradiol Decreases Cortical Reactive Astrogliosis after Brain Injury by a Mechanism Involving Cannabinoid Receptors

The neuroactive steroid estradiol reduces reactive astroglia after brain injury by mechanisms similar to those involved in the regulation of reactive gliosis by endocannabinoids. In this study, we have explored whether cannabinoid receptors are involved in the effects of estradiol on reactive astroglia. To test this hypothesis, the effects of estradiol, the cannabinoid CB1 antagonist/inverse agonist AM251, and the cannabinoid CB2 antagonist/inverse agonist AM630 were assessed in the cerebral cortex of male rats after a stab wound brain injury. Estradiol reduced the number of vimentin immunoreactive astrocytes and the number of glial fibrillary acidic protein immunoreactive astrocytes in the proximity of the wound. The effect of estradiol was significantly inhibited by the administration of either CB1 or CB2 receptor antagonists. The effect of estradiol may be in part mediated by alterations in endocannabinoid signaling because the hormone increased in the injured cerebral cortex the messenger RNA levels of CB2 receptors and of some of the enzymes involved in the synthesis and metabolism of endocannabinoids. These findings suggest that estradiol may decrease reactive astroglia in the injured brain by regulating the activity of the endocannabinoid system.

Ontogenetic profile of ectonucleotidase activities from brain synaptosomes of pilocarpine-treated rats

Adenosine, a well-known neuromodulator, can act as an endogenous anticonvulsant via the activation of adenosine A1 receptors. This adenine nucleoside can be produced in the synaptic cleft by the ectonucleotidase cascade, which includes the nucleoside triphosphate diphosphohydrolase (NTPDase) family and ecto-5′-nucleotidase. It has been previously reported that ectonucleotidase activities are increased in female adult rats submitted to the pilocarpine model of epilepsy. Several studies have suggested that the immature brain is less vulnerable to morphologic and physiologic alterations after status epilepticus (SE). Here, we evaluate the ectonucleotidase activities of synaptosomes from the hippocampus and cerebral cortex of male and female rats at different ages (7–9, 14–16 and 27–30-day old) submitted to the pilocarpine model of epilepsy. Our results show that ATP and ADP hydrolysis in the hippocampus and cerebral cortex were not altered by the pilocarpine treatment in female and male rats at 7–9, 14–16 and 27–30 days. There were no changes in AMP hydrolysis in female and male rats submitted to the model at different ages, but a significant increase in AMP hydrolysis (71%) was observed in synaptosomes from the cerebral cortex of male rats at 27–30 days. Pilocarpine-treated male rats (60–70-day old) presented an enhancement in ectonucleotidase activities in the synaptosomes of the cerebral cortex (33, 40 and 64% for ATP, ADP and AMP hydrolysis, respectively) and hippocampus (55, 98 and 101% for ATP, ADP and AMP hydrolysis, respectively). These findings highlight differences between the purinergic system of young and adult rats submitted to the pilocarpine model of epilepsy.

Zinc, copper and iron concentrations in cerebral cortex of male rats exposed to formaldehyde inhalation

Retrospective cohort studies and clinical findings have suggested effects of formaldehyde exposure on the central nervous system in anatomists, embalmers and pathologists. On the other hand, harmful effects of formaldehyde inhalation on the nervous system are not well documented. The concentrations of elements such as zinc, copper and iron within the cerebral cortex indicate whether physiological conditions are maintained. In this study, adult male albino Wistar rats were exposed to formaldehyde at different concentrations (0; 6.1; 12.2 mg · m −3) and during different periods of time (subacute-subchronic), and body weights were recorded weekly. Zinc, copper and iron concentrations were measured in the parietal cortex using atomic absorption spectrometry after wet ashing. We conclude that subacute or subchronic exposure to formaldehyde may cause growth retardation and alter zinc, copper and iron levels in the cerebral cortex.

Quantitative autoradiographic studies of relaxin binding in rat atria, uterus and cerebral cortex: characterization and effects of oestrogen treatment.

The binding characteristics of the relaxin receptor in rat atria, uterus and cortex were studied using a [33P]-labelled human gene 2 relaxin (B33) and quantitative receptor autoradiography. The binding kinetics of [33P]-human gene 2 relaxin (B33) were investigated in slide-mounted rat atrial sections. The binding achieved equilibrium after 60 min incubation at room temperature (23+/-1 degrees C) and dissociated slowly. The association and dissociation rate constants were 4.31+/-0.34x10(8) M(-1) x min(-1) and 1.55+/-0.38x10(-3) min(-1) respectively. Thus, the kinetic dissociation constant was 3.46+/-0.59 pM. Binding was saturable to a single population of non-interacting sites throughout atria, in uterine myometrium and the 5th layer of cerebral cortex. The binding affinities (pK(D)) of [33P]-human gene 2 relaxin (B33) were 8.92+/-0.09 in atrial myocardium and 8.79+/-0.04 in cerebral cortex of male rats, and 8.79+/-0.10 in uterine myometrium. Receptor densities in the cerebral cortex and atria were higher than in uterine myometrium, indicating that relaxin also has important roles in non-reproductive tissues. In male rats, treatment with 17beta-oestradiol (20 microg in 0.1 ml sesame oil s.c., 18-24 h) significantly decreased the density of relaxin receptors in atria and cerebral cortex. Identical treatment in female rats had no significant effect in atria and cerebral cortex, but it significantly increased the density of relaxin receptors in uterine myometrium. Relaxin binding was competitively displaced by porcine and rat native relaxins. Porcine native relaxin binds to the relaxin receptor in male rat atria (8.90+/-0.02), and cerebral cortex (8.90+/-0.03) and uterine myometrium (8.89+/-0.03) with affinities not significantly different from human gene 2 (B33) relaxin. Nevertheless, rat relaxin binds to the receptors with affinities (8.35+/-0.09 in atria, 8.22+/-0.07 in cerebral cortex and 8.48+/-0.06 in uterine myometrium) significantly less than human gene 2 (B33) and porcine relaxins. Quantitative receptor autoradiography is the method of choice for measurement of affinities and densities of relaxin receptor in atria, uterine myometrium and cerebral cortex. High densities were found in all these tissues. 17beta-oestradiol treatment produced complex effects where it increased the densities of relaxin receptors in uterus but decreased those in atria and cerebral cortex of the male rats, and had no effect on the atria and cerebral cortex of the female rats.

Fasting increases the expression of basic fibroblast growth factor (FGF-2) messenger ribonucleic acid in rat hypothalamus.

Basic fibroblast growth factor (FGF-2) has been isolated from the brain, but the regulation of FGF-2 synthesis in the brain is not yet fully understood. Since exogenously administered FGF-2 has been reported to suppress food intake as well as the secretion of gastric acid and pepsin in rats, we examined the effect of fasting on FGF-2 mRNA levels in the hypothalamus and the cerebral cortex of male rats, using RNase protection assay. Fasting for 72 h resulted in an approximately 2-fold increase in FGF-2 mRNA level in the hypothalamus but did not affect FGF-2 mRNA level in the cerebral cortex significantly. These findings support the hypothesis that FGF-2 plays a significant role in regulation of hypothalamic function.

Steroid hormone effects on NMDA receptor binding and NMDA receptor mRNA levels in the hypothalamus and cerebral cortex of the adult rat.

Previous work has demonstrated that N-methyl-D-aspartate (NMDA) is capable of stimulating luteinizing hormone release in a variety of species. Interestingly, the ability of NMDA to stimulate luteinizing hormone release is significantly compromised in castrated male and female rats as compared to intact animals. The purpose of the present study was to determine if a difference exists in the number or affinity of NMDA receptors in the hypothalamus of intact or castrated adult male and female rats and whether steroid replacement has any effect on NMDA receptor binding. NMDA receptor mRNA levels were also determined in the respective models. The cerebral cortex was used as a control to check for specificity of any observed differences. The number of NMDA binding sites in the hypothalamus was found to be approximately 25% of that found in the cerebral cortex and the equilibrium association constant was similar in both tissues. In the female rat, neither ovariectomy nor ovariectomy with estrogen pellet replacement or estrogen and progesterone injections altered NMDA receptor binding or the equilibrium association constant in the hypothalamus or cerebral cortex as compared to intact controls. Similar to the case in the female, NMDA receptor binding in the hypothalamus and cerebral cortex of male rats did not change after castration or after treatment with testosterone propionate. Neither ovariectomy nor ovariectomy with estradiol replacement brought about any change in the NMDA receptor mRNA levels in the hypothalamus. However, in the cerebral cortex ovariectomy with estrogen replacement brought about a small but significant increase in NMDA receptor mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetic properties of the 5α-reductase of testosterone in the purified myelin, in the subcortical white matter and in the cerebral cortex of the male rat brain

The 5α-reductase, the enzyme which converts testosterone into dihydrotestosterone (DHT), is present in several CNS structures of the rat. Recent reports from this laboratory indicate that the subcortical white matter and the myelin possess a 5α-eductase activity several times higher than that present in the cerebral cortex. Moreover, previous ontogenetic observations indicate that in all cerebral tissues examined (including the myelin) the 5α-reductase has a higher activity in immature animals.This study was performed in order to verify whether the differences in the 5α-reductase activity on the various brain components might be due to the presence of different concentrations of the same enzyme or to different isoenzymes. To this purpose, the kinetic properties Km and Vmax were measured in the purified myelin as well as in homogenates of the subcortical white matter and of the cerebral cortex, obtained from the brain of adult (60–90-day-old), immature (23-day-old), and aged (> 20-month-old) male rats.The results indicate that the enzymes present in the myelin, in the subcortical white matter and in the cerebral cortex of adult male rats possess a very similar apparent Km (1.93 ± 0.2, 2.72 ± 0.73 and 3.83 ± 0.49 μM respectively). On the contrary, the Vmax values obtained in the myelin (34.40 ± 5.54), in the white matter (19.57 ± 2.36) and in the cerebral cortex (6.47 ± 1.03 ng/h/mg protein) of adult animals have been found to be consistently different.Very similar Km values were found in the myelin obtained from the brain of immature and very old rats (2.14 ± 0.11 and 3.39 ± 0.75 μM respectively). The Vmax measured in the myelin purified from the immature rat brain (62.25 ± 4.52) showed a value which was much higher than that found in the myelin of adult animals (34.40 ± 5.54); a Vmax (34.31 ± 9.41) almost identical to that of adult animals was found in the myelin prepared from the brain of aged rats.

Gonadal influences on spinal cord and brain monoamines in male rats

Concentrations of norepinephrine (NE), dopamine (DA), 3,4-dihydroxy phenylacetic acid (DOPAC), serotonin (HT) and 5-hydroxyindoleacetic acid (HIAA) were measured by high-performance liquid chromatography—electrical detection (HPLC-ED) in homogenates of lumbosacral spinal cord, mediobasal hypothalamus and cerebral cortex of male rats. The effects of castration and testosterone propionate (TP) (20 μg/day × 2 days) were compared. Castrated animals had the highest levels of DA and DOPAC in the cerebral cortex and NE, HT and HIAA in the spinal cord, as well as decreased hypothalamic DOPAC. Testosterone treatment returned spinal cord monoamine concentrations to intact control levels. These findings point to the spinopetal monoaminergic pathways as sensitive targets for androgen action.

Effect of ?-endorphin on catecholamine levels in rat hypothalamus and cerebral cortex

The present paper deals with the effect of beta-endorphin on catecholamine content in the hypothalamus and cerebral cortex of male rats. beta-endorphin was found to decrease catecholamine content in the rat brain, with the degree of reduction depending on the brain topography and the time following the peptide administration. 5 min later no changes in catecholamine content were observed either in the hypothalamus or in the cerebral cortex. 20 min later beta-endorphin induced a statistically significant fall of catecholamine concentration in the hypothalamus. A tendency towards its decrease was also observed in the cerebral cortex. 60 min later beta-endorphin produced an insignificant decrease in catecholamine level in both brain areas under study. It may be therefore suggested that beta-endorphin-induced decrease of catecholamine content in the hypothalamus and cerebral cortex represents one of the mechanisms underlying beta-endorphin stimulating action on a number of trophic functions of the hypophysis.

Sex hormone receptors in the hypothalamus and their role in sexual differentiation of the male rat brain

In this investigation, changes in the level of receptors for sex hormones in the hypothalamus and cerebral cortex of male rats were studied on the first through fifth days of postnatal life, and the results obtained were compared with the levels of luteinizing hormone and sex hormones in the peripheral blood in order to discover any correlation between these parameters. 2,4,6,7,-/sup 3/H-estradiol-17..beta.. and 1,2,6,7-/sup 3/H-testosterone were used as labeled hormones. The values of the association constant and concentration of specific binding sites for estradiol and testosterone in hypothalamus and cerebral cortex of male rats during neonatal development is shown. It is found that in male rats on the first day after birth, receptors for estradiol and testosterone are present and they enable the action both of the testicular hormone and that of estradiol to be realized.

Plasticity in the 904-day-old male rat cerebral cortex

Ten pairs of male Long-Evans rats living in nonenriched environments (3 rats per small cage) were transferred to either enriched environments (10 rats per large cage plus “toys”) or nonenriched environments (2 rats per small cage) at 766 days of age. One hundred and thirty-eight days later, at 904 days of age, the cerebral cortical thickness from these animals was measured on projected, 10-μm, thioninestained, transverse sections. Although the thickness in the enriched rats was greater than in the nonenriched rats in all sections through the frontal, parietal, and occipital cortices, the 4 to 10% differences were statistically significantly different in only the frontal and occipital cortices. Right greater than left cortical thickness differences were not statistically significant in either the enriched or the nonenriched animals by 904 days of age. Neuron and glial counts were made on enlarged photographs of area 18 in the occipital cortex on 6-μm-thick, luxol fast blue-stained sections. No significant differences in cell counts were noted between the enriched and nonenriched animals. No significant differences in neuronal counts were found among 108-, 650- (from previous experiments), and the 904-day-old nonenriched rats. The notable findings were the plasticity of the extremely old, enriched rats' occipital cortex and the lack of the loss of neurons in cerebral cortical area 18, whether or not the environments were enriched. These results showed that the cerebral cortex remained structurally plastic throughout the lifetime of the organism.