Brain Of Adult Male Rats Research Articles

Neurotoxic and Genotoxic Potentials of Short Term Copper Exposure in Adult Male Albino Rats (Biochemical, Histopathological, Immunohistochemical and Genotoxic Study)

Objective: Although copper is an essential micronutrient involved in a variety of biological processes indispensable for sustaining life yet it can be toxic when administered in excess. Material and Methods: Thirty six adult male albino rats were equally divided into three groups; the first group was used as a negative control, the second group received normal saline intraperitoneal (positive control group) and the third group received copper chloride 7mg/kg twice weekly intraperitoneal for 8 weeks (treated group). At the end of the experimental period, blood was withdrawn for measuring serum malondialdhyde (MDA) and catalase (CAT), then the rats were sacrificed and the brain was examined by light microscope for detecting histopathological changes. Brain sections were examined immunohistochemically for the detection of the apoptotic BaX protein and finally, the bone marrow was examined for detection of chromosomal aberrations. Results: In Cu chloride treated group (group III), there was a significant elevation in serum malondialdehyde & a significant decrease in serum catalase. Histopathological changes were in the form of increased cellularity of astrocytes, swelling of astrocytes that showed dense eosinophilic cytoplasm, with pyknotic nuclei and multiple apoptotic bodies. Also, there were degenerated neurons with deep eosinophilc cytoplasm using light microscope and BaX showed strong immunoreactions in the brain. Bone marrow showed significant increase in all types of chromosomal aberrations after 8 weeks of Cu chloride treatment. Conclusion: From the previous results, it can be concluded that Cu chloride exposure can induce oxidative stress changes in the form of a significant increase in MDA and significant decrease in CAT enzyme as well as histopathological changes in the brain and genotoxicity in adult male albino rats after short term exposure.

The impact of prenatal stress on insulin-like growth factor-1 and pro-inflammatory cytokine expression in the brains of adult male rats: The possible role of suppressors of cytokine signaling proteins

Stress, inflammation and the reduced expression of neurotrophic factors are risk factors for depression. The objective of this study was to determine if prenatal stress affects IGF-1 – cytokine interactions by influencing suppressors of cytokine signaling (SOCS) in the brains of adult rats, in basal conditions and after acute lipopolysaccharide (LPS) treatment. We demonstrated that prenatal stress leads to depression-like behavior, decreased IGF-1, increased IL-1β, TNF-α and IFN-γ release and disturbed SOCS-1, SOCS-2 and SOCS-3 expression in the hippocampus and frontal cortex of adult offspring. Furthermore, prenatal stress enhances the brain response to LPS-evoked inflammatory challenges.

Shifts in Hormonal Stress Reactivity during Adolescence Are Not Associated with Changes in Glucocorticoid Receptor Levels in the Brain and Pituitary of Male Rats

Preadolescent animals display protracted hormonal stress responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis compared to adults. Though the mechanisms that underlie this shift in stress reactivity are unknown, reduced glucocorticoid-dependent negative feedback on the HPA axis has been posited to contribute to this differential responsiveness. As the glucocorticoid receptors (GRs) are integral to this feedback response, we hypothesize that prior to puberty there will be fewer GRs in the neural-pituitary network that mediate negative feedback. To test this hypothesis we measured GR protein levels in the brains of preadolescent (28 days old), midadolescent (40 days old) and adult (77 days old) male rats via immunohistochemistry. Additionally, we assessed stress-induced plasma adrenocorticotropic hormone and corticosterone in prepubertal (30 days old) and adult (70 days old) male rats and examined GR protein levels via Western blot in the brain and pituitary. We found that despite substantial adolescent-related changes in hormonal responsiveness, no significant differences were found between these ages in GR protein levels in regions that are important in negative feedback, including the medial prefrontal cortex, paraventricular nucleus of the hypothalamus, hippocampal formation, and pituitary. These data indicate that the extended hormonal stress response exhibited by preadolescent animals is independent of significant pubertal changes in GR protein levels.

Presynaptic inhibition of the release of multiple major central nervous system neurotransmitter types by the inhaled anaesthetic isoflurane

Presynaptic effects of general anaesthetics are not well characterized. We tested the hypothesis that isoflurane exhibits transmitter-specific effects on neurotransmitter release from neurochemically and functionally distinct isolated mammalian nerve terminals. Nerve terminals from adult male rat brain were prelabelled with [(3)H]glutamate and [(14)C]GABA (cerebral cortex), [(3)H]norepinephrine (hippocampus), [(14)C]dopamine (striatum), or [(3)H]choline (precursor of [(3)H]acetylcholine; striatum). Release evoked by depolarizing pulses of 4-aminopyridine (4AP) or elevated KCl was quantified using a closed superfusion system. Isoflurane at clinical concentrations (<0.7 mM; ~2 times median anaesthetic concentration) inhibited Na(+) channel-dependent 4AP-evoked release of the five neurotransmitters tested in a concentration-dependent manner. Isoflurane was a more potent inhibitor [expressed as IC(50) (SEM)] of glutamate release [0.37 (0.03) mM; P<0.05] compared with the release of GABA [0.52 (0.03) mM], norepinephrine [0.48 (0.03) mM], dopamine [0.48 (0.03) mM], or acetylcholine [0.49 (0.02) mM]. Inhibition of Na(+) channel-independent release evoked by elevated K(+) was not significant at clinical concentrations of isoflurane, with the exception of dopamine release [IC(50)=0.59 (0.03) mM]. Isoflurane inhibited the release of the major central nervous system neurotransmitters with selectivity for glutamate release, consistent with both widespread inhibition and nerve terminal-specific presynaptic effects. Glutamate release was most sensitive to inhibition compared with GABA, acetylcholine, dopamine, and norepinephrine release due to presynaptic specializations in ion channel expression, regulation, and/or coupling to exocytosis. Reductions in neurotransmitter release by volatile anaesthetics could contribute to altered synaptic transmission, leading to therapeutic and toxic effects involving all major neurotransmitter systems.

Expression and distribution of TRPV2 in rat brain

Transient receptor potential (TRP) proteins are non-selective cation channels that mediate sensory transduction. The neuroanatomical localization and the physiological roles of isoform TRPV2 in the rodent brain are largely unknown. We report here the neuroanatomical distribution of TRPV2 in the adult male rat brain focusing on the hypothalamus and hindbrain regions involved in osmoregulation, autonomic function and energy metabolism. For this we utilized immunohistochemistry combined with brightfield microscopy. In the forebrain, the densest immunostaining was seen in both the supraoptic nucleus (SON) and the magnocellular division of the paraventricular nucleus (PVN) of the hypothalamus. TRPV2 immunoreactivity was also seen in the organum vasculosum of the lamina terminalis, the median preoptic nucleus and the subfornical organ, in addition to the arcuate nucleus of the hypothalamus (ARH), the medial forebrain bundle, the cingulate cortex and the globus pallidus to name a few. In the hindbrain, intense staining was seen in the nucleus of the solitary tract, hypoglossal nucleus, nucleus ambiguous, and the rostral division of the ventrolateral medulla (RVLM) and some mild staining in the area prostrema. To ascertain the specificity of the TRPV2 antibody used in this paper, we compared the TRPV2 immunoreactivity of wildtype (WT) and knockout (KO) mouse brain tissue. Double immunostaining with arginine vasopressin (AVP) using confocal microscopy showed a high degree of colocalization of TRPV2 in the magnocellular SON and PVN. Using laser capture microdissection (LCM) we also show that AVP neurons in the SON contain TRPV2 mRNA. TRPV2 was also co-localized with dopamine beta hydroxylase (DBH) in the NTS and the RVLM of the hindbrain. Based on our results, TRPV2 may play an important role in several CNS networks that regulate body fluid homeostasis, autonomic function, and metabolism.

Effect of time period after boric acid injection on 10B absorption in different regions of adult male rat's brain

Distribution of 10B in different regions of rat normal brain was studied. Two groups were chosen as control and trial. Trial group received 2ml of neutral boron compound. 2, 4 and 6 h after the injection brain removed, coronal sections of forebrain, midbrain and hindbrain were sandwiched between two pieces of polycarbonate. Autoradiography plots of 10B distribution showed significant differences in three regions with the highest 10B concentration in the forebrain during 4h after injection.

Antioxidant activities of Punica granatum (pomegranate) peel extract on brain of rats

Methanol extract of Punica granatum (pomegranate) peel was screened for its antioxidant activity on brain of adult male Wister albino rats. The antioxidant activity was determined by measuring reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase. In addition, hydrogen peroxide (H2O2), nitric oxide (NO) and lipid peroxidation (MDA) were also measured in brain homogenate. Pomegranate peel treatment resulted in marked increase in most antioxidant parameters with reduction in oxidant H2O2, NO and MDA. On the basis of the previous results it can be concluded that pomegranate methanol peel extract is a promising natural product, which could be useful for the prevention of neurodegenerative diseases caused by oxidative stress. Key words: Pomegranate peel, antioxidant enzymes, brain, rats.

Distribution of PDE8A in the nervous system of the Sprague-Dawley rat

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling. Little is known of the distribution and function of the cyclic adenosine monophosphate (cAMP) hydrolyzing PDE8A family. Employing immunohistochemistry and Western blots this study maps the distribution of PDE8A in the brain of adult male Sprague-Dawley rats and in the trigeminal ganglion. PDE8A was confined to neuronal perikaryal cytoplasm and to processes extending from those perikarya. The neurons exhibiting PDE8A-immunoreactivity were widely distributed in the forebrain, brain stem, and cerebellum. Strongly immunoreactive neurons were located in the olfactory bulb, the septal area, zona incerta, and reticular nucleus of the thalamus. Less immunoreactivity was seen in the hippocampus and cerebral cortex. Intense staining was detected in both the substantia nigra and the sensory trigeminal nucleus. In cerebellum PDE8A immunoreactivity was located not only in the Purkinje cells, but also in the granular cells as well as the parallel fibres in the molecular layer. PDE8A immunoreactivity was represented in the epithelial lining of the choroids plexus, the dura mater, and the neurons of the trigeminal ganglion. The localization of the cAMP degrading PDE8A may indicate a role for PDE8A in cAMP signaling related to pain transmission, motor function, cognition and olfaction.

Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain

Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor α (ERα) mRNA expression and decreased ERα promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. The maintenance of methylated or demethylated states of some genes in the adult brain by the presence of steroid hormones may play a role in the homeostatic regulation of behaviorally relevant systems.

The role of hypoxia-inducible factor-1α, aquaporin-4, and matrix metalloproteinase-9 in blood-brain barrier disruption and brain edema after traumatic brain injury

The present study investigated the role of hypoxia-inducible factor-1α (HIF-1α), aquaporin-4 (AQP-4), and matrix metalloproteinase-9 (MMP-9) in blood-brain barrier (BBB) permeability alterations and brain edema formation in a rodent traumatic brain injury (TBI) model. The brains of adult male Sprague-Dawley rats (400-425 g) were injured using the Marmarou closed-head force impact model. Anti-AQP-4 antibody, minocycline (an inhibitor of MMP-9), or 2-methoxyestradiol (2ME2, an inhibitor of HIF-1α), was administered intravenously 30 minutes after injury. The rats were killed 24 hours after injury and their brains were examined for protein expression, BBB permeability, and brain edema. Expression of HIF-1α, AQP-4, and MMP-9 as well as expression of the vascular basal lamina protein (laminin) and tight junction proteins (zona occludens-1 and occludin) was determined by Western blotting. Blood-brain barrier disruption was assessed by FITC-dextran extravasation, and brain edema was measured by the brain water content. Significant (p < 0.05) edema and BBB extravasations were observed following TBI induction. Compared with sham-operated controls, the injured animals were found to have significantly (p < 0.05) enhanced expression of HIF-1α, AQP-4, and MMP-9, in addition to reduced amounts (p < 0.05) of laminin and tight junction proteins. Edema was significantly (p < 0.01) decreased after inhibition of AQP-4, MMP-9, or HIF-1α. While BBB permeability was significantly (p < 0.01) ameliorated after inhibition of either HIF-1α or MMP-9, it was not affected following inhibition of AQP-4. Inhibition of MMP reversed the loss of laminin (p < 0.01). Finally, while inhibition of HIF-1α significantly (p < 0.05) suppressed the expression of AQP-4 and MMP-9, such inhibition significantly (p < 0.05) increased the expression of laminin and tight junction proteins. The data support the notion that HIF-1α plays a role in brain edema formation and BBB disruption via a molecular pathway cascade involving AQP-4 and MMP-9. Pharmacological blockade of this pathway in patients with TBI may provide a novel therapeutic strategy.

Fragrant Dioxane Derivatives Identify β1-Subunit-containing GABAA Receptors

Nineteen GABA(A) receptor (GABA(A)R) subunits are known in mammals with only a restricted number of functionally identified native combinations. The physiological role of beta1-subunit-containing GABA(A)Rs is unknown. Here we report the discovery of a new structural class of GABA(A)R positive modulators with unique beta1-subunit selectivity: fragrant dioxane derivatives (FDD). At heterologously expressed alpha1betaxgamma2L (x-for 1,2,3) GABA(A)R FDD were 6 times more potent at beta1- versus beta2- and beta3-containing receptors. Serine at position 265 was essential for the high sensitivity of the beta1-subunit to FDD and the beta1N286W mutation nearly abolished modulation; vice versa the mutation beta3N265S shifted FDD sensitivity toward the beta1-type. In posterior hypothalamic neurons controlling wakefulness GABA-mediated whole-cell responses and GABAergic synaptic currents were highly sensitive to FDD, in contrast to beta1-negative cerebellar Purkinje neurons. Immunostaining for the beta1-subunit and the potency of FDD to modulate GABA responses in cultured hypothalamic neurons was drastically diminished by beta1-siRNA treatment. In conclusion, with the help of FDDs we reveal a functional expression of beta1-containing GABA(A)Rs in the hypothalamus, offering a new tool for studies on the functional diversity of native GABA(A)Rs.

Methamphetamine-Induced Behavioral and Physiological Effects in Adolescent and Adult HIV-1 Transgenic Rats

We recently reported that six consecutive days of treatment with a moderate dose of methamphetamine (METH) induced greater behavioral sensitization in adult HIV-1 transgenic (HIV-1 Tg) rats than in adult Fischer 344/NHsd (F344) non-transgenic, wild-type control animals. In the present study, we evaluated the effects of a moderate dose of METH on the brains of adolescent versus adult HIV-1 Tg male rats using both behavioral (METH-induced, stereotypic head movement) and physiological (rectal body temperature) parameters. We found that both the acute and behavior-sensitizing effects of METH were greater in HIV-1 Tg rats compared with controls and also in adolescent rats compared with adult animals, regardless of HIV-1 status. We determined that acute hyperthermic effects of METH as well as tolerance to METH-induced hyperthermia were greater in HIV-1 Tg rats than in controls. Taken together, these results suggest that both the neuroadaptations seen in HIV infection and the immaturity of the adolescent brain are associated with increased sensitivity to the psychoactive and behavior-sensitizing properties of METH. Thus, HIV-infected individuals and adolescents may be more vulnerable to the development of METH abuse and dependence than non-infected individuals and adults.

Recombinant truncated and microsomal heme oxygenase-1 and -2: differential sensitivity to inhibitors

Recombinant truncated forms of heme oxygenase-1 and -2 (HO-1 and HO-2) were compared with their crude microsomal counterparts from brain and spleen tissue of adult male rats with respect to their inhibition by azole-based, nonporphyrin HO inhibitors. The drugs tested were an imidazole-alcohol, an imidazole-dioxolane, and a triazole-ketone. Both the recombinant and crude forms of HO-2 were similarly inhibited by the 3 drugs. The crude microsomal spleen form of HO-1 was more susceptible to inhibition than was the truncated recombinant form. This difference is attributed to the extra amino acids in the full-length enzyme. These observations may be relevant in the design of drugs as inhibitors of HO and other membrane proteins.

Effect of Complete Maternal and Littermate Deprivation on Morphine-Induced Fos-Immunoreactivity in the Adult Male Rat Brain

Previous research has demonstrated that rats reared in isolation from their dam and littermates show altered behavioral responsiveness to both natural and drug-mediated rewards. This study examined the effects of complete maternal deprivation through the use of artificial rearing on neural activation after acute morphine exposure in adulthood. Male rats were either artificially reared (AR) or maternally reared (MR) from postnatal day 5 to 21. In adulthood (4 mo old), rats received a single injection of morphine sulfate (10 mg/kg) or equivolume saline 2 h before perfusion and brain extraction. Neural activation was quantified using Fos immunohistochemistry. Analyses of several brain regions revealed a consistent pattern of differences between AR and MR rats. Specifically, relative to MR rats, AR rats showed significantly greater morphine-induced Fos-immunoreactivity in brain regions associated with the mesocorticolimbic "reward" pathway. These results support the hypothesis that functional activity in reward neurocircuitry can be altered by early life experience.

MicroRNAs Show Mutually Exclusive Expression Patterns in the Brain of Adult Male Rats

BackgroundThe brain is a major site of microRNA (miRNA) gene expression, but the spatial expression patterns of miRNAs within the brain have not yet been fully covered.Methodology/Principal FindingsWe have characterized the regional expression profiles of miRNAs in five distinct regions of the adult rat brain: amygdala, cerebellum, hippocampus, hypothalamus and substantia nigra. Microarray profiling uncovered 48 miRNAs displaying more than three-fold enrichment between two or more brain regions. Notably, we found reciprocal expression profiles for a subset of the miRNAs predominantly found (> ten times) in either the cerebellum (miR-206 and miR-497) or the forebrain regions (miR-132, miR-212, miR-221 and miR-222).Conclusions/SignificanceThe results indicate that some miRNAs could be important for area-specific functions in the brain. Our data, combined with previous studies in mice, provides additional guidance for future investigations of miRNA functions in the brain.

Interactive effect of excitotoxic injury and dietary restriction on neurogenesis and neurotrophic factors in adult male rat brain

Dietary restriction (DR) is known to have potential health benefits including enhanced resistance of neurons to excitotoxic, oxidative and metabolic insults, cancer, stress, diabetes, reduced morbidity, and increased life span. In the present study, we examined the effect of DR (alternate day feeding regimen) on neurogenesis, expression of immature neuronal marker polysialic acid neural cell adhesion molecule (PSA-NCAM) and neurotrophic factors from different brain regions such as subventricular zone (SVZ), subgranular zone (SGZ) of hippocampus, median eminence arcuate (ME-ARC) region of hypothalamus, and piriform cortex (PIR) of adult male rats and further challenged ad libitum fed (AL) and DR rats with pilocarpine to induce excitotoxic injury. The quantitative analysis of bromodeoxyuridine (BrdU) labeling revealed a significant increase in the proliferation rate of neuronal progenitor cells from discrete brain regions in DR rats with and without pilocarpine induced seizures as compared to AL rats. DR significantly enhanced the expression of PSA-NCAM and neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). There was a marked reduction in neuronal cell death in SVZ and PIR cortex after pilocarpine administration in DR rats. These results add to the accumulating evidence that DR may be an effective intervention to enhance the resistance of brain to excitotoxic injury.

Increasing of 5alpha-reductase type 1 mRNA levels as an important mechanism in interaction effects of testosterone and morphine at pain and tolerance in the rat

It has been shown that morphine administration decreases brain testosterone levels probably through the activation of 5alpha-reductase (5α-R) enzyme in the brain. Recently, we indicated that finasteride, a 5α - reductase inhibitor, potentiates antinociceptive effects of morphine and prevents the development of morphine tolerance. In this work, we studied the effects of acute (10 mg/kg, i.p.) and chronic (20 mg/kg, i.p. once daily for 4 days) morphine on the 5α-R type 1 (5α-R1) mRNA levels in the adult male rat brain, using an RT-PCR method, in addition to the determination of brain testosterone levels 30 minutes following morphine. The results of our study revealed an increase in the 5α R1 mRNA levels following both acute and chronic morphine administration. It was also founded that testosterone concentration in the brain is reduced 30 minutes following morphine administration. It was concluded that the decreasing effect of morphine exposure on the brain testosterone is through an increase in the brain 5α-R1 mRNA levels. Moreover, tolerance to this effect is not developed in chronic morphine administration. Therefore, morphine may play a regulatory role in metabolism of neurosteroids, especially testosterone, in the brain which may occur at transcription level and/or translation level.This abstract will also be presented as an Oral Paper Presentation. Refer to the daily Schedule-At-A-Glance for presentation time and location. It has been shown that morphine administration decreases brain testosterone levels probably through the activation of 5alpha-reductase (5α-R) enzyme in the brain. Recently, we indicated that finasteride, a 5α - reductase inhibitor, potentiates antinociceptive effects of morphine and prevents the development of morphine tolerance. In this work, we studied the effects of acute (10 mg/kg, i.p.) and chronic (20 mg/kg, i.p. once daily for 4 days) morphine on the 5α-R type 1 (5α-R1) mRNA levels in the adult male rat brain, using an RT-PCR method, in addition to the determination of brain testosterone levels 30 minutes following morphine. The results of our study revealed an increase in the 5α R1 mRNA levels following both acute and chronic morphine administration. It was also founded that testosterone concentration in the brain is reduced 30 minutes following morphine administration. It was concluded that the decreasing effect of morphine exposure on the brain testosterone is through an increase in the brain 5α-R1 mRNA levels. Moreover, tolerance to this effect is not developed in chronic morphine administration. Therefore, morphine may play a regulatory role in metabolism of neurosteroids, especially testosterone, in the brain which may occur at transcription level and/or translation level. This abstract will also be presented as an Oral Paper Presentation. Refer to the daily Schedule-At-A-Glance for presentation time and location.

Long-term Transgene Expression in the Central Nervous System Using DNA Nanoparticles

This study demonstrates proof of concept for delivery and expression of compacted plasmid DNA in the central nervous system. Plasmid DNA was compacted with polyethylene glycol substituted lysine 30-mer peptides, forming rod-like nanoparticles with diameters between 8 and 11 nm. Here we show that an intracerebral injection of compacted DNA can transfect both neurons and glia, and can produce transgene expression in the striatum for up to 8 weeks, which was at least 100-fold greater than intracerebral injections of naked DNA plasmids. Bioluminescent imaging (BLI) of injected animals at the 11th postinjection week revealed significantly higher transgene activity in animals receiving compacted DNA plasmids when compared to animals receiving naked DNA. There was minimal evidence of brain inflammation. Intrastriatal injections of a compacted plasmid encoding for glial cell line-derived neurotrophic factor (pGDNF) resulted in a significant overexpression of GDNF protein in the striatum 1-3 weeks after injection.

Dose-dependent effects of corticosterone on nuclear glucocorticoid receptors and their binding to DNA in the brain and pituitary of the rat

The glucocorticoid receptor (GR) is a transcription factor which regulates glucocorticoid-mediated negative feed-back of the HPA axis. In this study, we have investigated the dose-dependent effects of corticosterone on nuclear GR and GR–DNA binding in the brain and pituitary of adult adrenalectomized male rats. Rats were injected with either saline (1 ml/kg, i.p.) or corticosterone (0.1, 0.3, and 1 mg/kg, i.p.). Nuclear GR and GR–DNA binding were measured in nuclear extracts from hippocampus, hypothalamus, prefrontal cortex, amygdala and pituitary using Western immunoblotting and ELISA, respectively. We found that the dose-dependent effects of corticosterone on nuclear GR and GR–DNA binding are similar across all the areas we analyzed, although at lower levels of corticosterone changes were observed only in the hippocampus. These data have important implications for our understanding of tissue specificity of glucocorticoid action including the corticosteroid-mediated negative feed-back response of the HPA axis.

Period gene expression in the diurnal degu (Octodon degus) differs from the nocturnal laboratory rat (Rattus norvegicus)

Recent data suggest that both nocturnal and diurnal mammals generate circadian rhythms using similarly phased feedback loops involving Period genes in the suprachiasmatic nuclei (SCN) of the hypothalamus. These molecular oscillations also exist in the brain outside of the SCN, but the relationship between SCN and extra-SCN oscillations is unclear. We hypothesized that a comparison of "diurnal" and "nocturnal" central nervous system Per rhythms would uncover differences in the underlying circadian mechanisms between these two chronotypes. Therefore, this study compared the 24-h oscillatory patterns of Per1 and Per2 mRNA in the SCN and putative striatum and cortex of Octodon degus (degu), a diurnal hystricognath rodent, with those of the nocturnal laboratory rat, Rattus norvegicus. The brains of adult male degus and rats were collected at 2-h intervals across 24 h in entrained light-dark and constant darkness conditions, and sections were analyzed via in situ hybridization. In the SCN, degu Per1 and Per2 hybridization signal exhibited 24-h oscillatory patterns similar in phasing to those seen in other rodents, with peaks occurring during the light period and troughs during the dark period. However, Per1 remained elevated for five fewer hours in the degu than in the rat, and Per2 remained elevated for two fewer hours in the degu. In brain areas outside of the SCN, the phase of Per2 hybridization signal rhythms in the degu were 180 degrees out of phase with those found in the rat, and Per1 hybridization signal lacked significant rhythmicity. These results suggest that, while certain basic components of the transcriptional-translational feedback loop generating circadian rhythms are similar in diurnal and nocturnal mammals, there are variations that may reflect adaptations to circadian niche.