Biomedical subjects

R Quirion

Publications and source records attributed to R Quirion.

At least 19 recordsLinked to original sources

PubMed2001

Application of in vivo microdialysis to the study of cholinergic systems.

The application of in vivo microdialysis to the study of acetylcholine (ACh) release has contributed greatly to our understanding of cholinergic brain systems. This article reviews standard experimental procedures for dialysis probe selection and implantation, perfusion parameters, neurochemical detection, and data analysis as they relate to microdialysis assessments of cholinergic function. Particular attention is focused on the unique methodological considerations that arise when in vivo microdialysis is dedicated expressly to the recovery and measurement of ACh as opposed to other neurotransmitters. Limitations of the microdialysis technique are discussed, as well as methodological adaptations that may prove useful in overcoming these limitations. This is followed by an overview of recent studies in which the application of in vivo microdialysis has been used to characterize the basic pharmacology and physiology of cholinergic neurons. Finally, the usefulness of the microdialysis approach for testing hypotheses regarding the cholinergic systems' involvement in cognitive processes is examined. It can be concluded that, in addition to being a versatile and practical method for studying the neurochemistry of cholinergic brain systems, in vivo microdialysis represents a valuable tool in our efforts to better comprehend ACh's underlying role in a variety of behavioral processes.

Acetylcholine↗

PubMed2001

Say NO to Alzheimer's disease: the putative links between nitric oxide and dementia of the Alzheimer's type.

Alzheimer's disease (AD) is the most common form of dementia, with progressive cognitive deficits being the primary symptom. AD is neuropathologically characterized by amyloid and neurofibrillary tangle depositions, basal forebrain cholinergic deficit, and extensive neuronal loss and synaptic changes in the cortex and hippocampus. Mutations of amyloid precursor protein or presenilin genes or apolipoprotein E gene polymorphism appear to affect amyloid formation, which in turn causes neuronal death via a number of possible mechanisms, including Ca(2+) homeostasis disruption, oxidative stress, excitotoxicity, energy depletion, neuro-inflammation and apoptosis. Nitric oxide (NO) is an enzymatic product of nitric oxide synthase, which exists in three isoforms. In addition to its vasoactive and immunological properties, NO has significant neurophysiological functions. However, NO can also be neurotoxic primarily due to its free radical properties, and it has been implicated in neurodegenerative diseases. Interestingly, there is increasing evidence that NO may have a role in the aforementioned AD pathogenetic mechanisms, and putative links between NO and AD are beginning to be recognized. This review focuses on these issues highlighting the possible relevance of NO in AD, either as a neuroprotective or neurotoxic agent.

Alzheimer Disease↗

PubMed2000

Insulin-like growth factor-I and its receptor in the frontal cortex, hippocampus, and cerebellum of normal human and alzheimer disease brains.

Assimilated evidence indicates that the neurotoxic potential of amyloid beta (Abeta) peptide and an alteration in the level of growth factor(s) may possibly be involved in the loss of neurons observed in the brain of patients suffering from Alzheimer disease (AD), the prevalent cause of dementia in the elderly. In the present study, using receptor binding assays and immunocytochemistry, we evaluated the pharmacological profile of insulin-like growth factor-I (IGF-I) receptors and the distribution of IGF-I immunoreactivity in the frontal cortex, hippocampus, and cerebellum of AD and age-matched control brains. In control brains, [(125)I]IGF-I binding was inhibited more potently by IGF-I than by Des(1-3)IGF-I, IGF-II or insulin. The IC(50) values for IGF-I in the frontal cortex, hippocampus, and cerebellum of the normal brain did not differ significantly from the corresponding regions of the AD brain. Additionally, neither K(D) nor B(max) values were found to differ in the hippocampus of AD brains from the controls. At the regional levels, [(125)I]IGF-I binding sites in the AD brain also remained unaltered compared to the controls. As for the peptide itself, IGF-I immunoreactivity, in normal control brains, was evident primarily in a subpopulation of astrocytes in the frontal cortex and hippocampus, and in certain Purkinje cells of the cerebellum. In AD brains, a subset of Abeta-containing neuritic plaques, apart from astrocytes, exhibit IGF-I immunoreactivity. These results, taken together, suggest a role for IGF-I in compensatory plasticity and/or survival of the susceptible neurons in AD brains.

Aged↗

PubMed2000

Insulin-like growth factor-1-induced phosphorylation of the forkhead family transcription factor FKHRL1 is mediated by Akt kinase in PC12 cells.

The Forkhead family transcription factor FKHRL1, a mammalian homolog of DAF16 in the nematode Caenorhabditis elegans, is an inducer of apoptosis in its unphosphorylated form and was recently reported as a substrate of Akt kinases. Insulin-like growth factor (IGF-1) is a potent stimulant of Akt kinase, leading to inhibition of the apoptotic pathway. In this study, we characterized the phosphorylation of FKHRL1 induced by IGF-1 in PC12 cells and various neuronal cell types and examined the potential role of Akt in this regard. IGF-1 rapidly induced the phosphorylation of Akt and FKHRL1 in PC12 cells. The phosphorylation of Akt and FKHRL1 induced by 10 nm IGF-1 was inhibited by the phosphatidylinositide 3-kinase (PI3K) inhibitors wortmannin (0.25-2 microm) and LY294002 (12.5-100 microm), but not by the MEK inhibitor PD98059 (50 microm) or the p70 S6 kinase pathway inhibitor rapamycin (50 nm), suggesting that the phosphorylation of FKHRL1 induced by IGF-1 is mediated by the PI3K pathway. As observed for IGF-1, an in vitro kinase assay with purified active Akt kinase demonstrated that the kinase is capable of directly phosphorylating FKHRL1 at Thr(32) and Ser(253), leading to inhibition of its pro-apoptotic properties. Moreover, transient expression of constitutively active Akt (MS-Akt, where MS is a myristylation signal) increased the phosphorylation of FKHRL1, whereas the expression of kinase-dead Akt (M179A Akt) attenuated the phosphorylation of FKHRL1 induced by 10 nm IGF-1 in PC12 cells. Interestingly, FKHRL1 co-immunoprecipitated with Akt in PC12 cells, indicating that these two proteins can associate in these cells. As IGF-1 also induced the phosphorylation of FKHRL1 in primary cortical and cerebellar neuronal cultures, these data, taken together, demonstrate that IGF-1, acting via the PI3K/Akt kinase pathway, can regulate the phosphorylation of FKHRL1, leading to inhibition of this apoptotic transcription factor in neuronal cells.

3T3 Cells↗

PubMed2000

Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression.

Exogenous neuropeptide Y (NPY) reduces experimental anxiety in a wide range of animal models. The generation of an NPY-transgenic rat has provided a unique model to examine the role of endogenous NPY in control of stress and anxiety-related behaviors using paradigms previously used by pharmacological studies. Locomotor activity and baseline behavior on the elevated plus maze were normal in transgenic subjects. Two robust phenotypic traits were observed. (i) Transgenic subjects showed a markedly attenuated sensitivity to behavioral consequences of stress, in that they were insensitive to the normal anxiogenic-like effect of restraint stress on the elevated plus maze and displayed absent fear suppression of behavior in a punished drinking test. (ii) A selective impairment of spatial memory acquisition was found in the Morris water maze. Control experiments suggest these traits to be independent. These phenotypic traits were accompanied by an overexpression of prepro-NPY mRNA and NPY peptide and decreased NPY-Y1 binding within the hippocampus, a brain structure implicated both in memory processing and stress responses. Data obtained using this unique model support and extend a previously postulated anti-stress action of NPY and provide novel evidence for a role of NPY in learning and memory.

Animals↗

PubMed2000

Stimulation of protein kinase C modulates insulin-like growth factor-1-induced akt activation in PC12 cells.

Activation of protein kinase C (PKC) plays an important role in the negative regulation of receptor signaling, but its effect on insulin-like growth factor-1 (IGF-1) receptor signaling remains unclear. In this study, we characterized the intracellular pathways involved in IGF-1-induced activation of Akt and evaluated the effects of the PKC activator phorbol 12-myristate 13-acetate (PMA) on the Akt activation by IGF-1. IGF-1 induced a time- and concentration-dependent activation of Akt. The effect of IGF-1 was blocked by the phosphatidylinositide 3-kinase (PI3K) inhibitors LY294002 (50 micrometer) and wortmannin (0.5 micrometer), but not by the MEK inhibitor PD98059 (50 micrometer) or the p70 S6 kinase pathway inhibitor rapamycin (50 nm), suggesting that the stimulation of Akt by IGF-1 is mediated by the PI3K pathway. Interestingly, cotreatment with PMA (400 nm) attenuated IGF-1-induced activation of Akt. The attenuation was blocked completely by the PKC inhibitor GO6983 (0.5 micrometer), but only partially by the MEK inhibitor PD98059 (50 micrometer), indicating that MAPK-dependent and -independent pathways are involved. PMA induced the activation of PKC in PC12 cells, and this induction was blocked by GO6983. These data further support the role of PKC in the effect of PMA. Moreover, PKCdelta is likely involved in the action of PMA on the basis of data obtained using isoform-specific inhibitors such as rottlerin. PMA also decreased IGF-1-induced tyrosine phosphorylation of insulin receptor substrate-1 and its association with PI3K. Taken together, these results suggest, for the first time, that stimulation of PKC modulates IGF-1-induced activation of Akt.

Animals↗

PubMed2000

Dopamine D-5 receptor modulates hippocampal acetylcholine release.

Dopamine is intimately involved in cognitive processes in the brain. Of the several subtypes of dopamine receptors, the possible role of dopamine D1-like receptors in brain functions, especially in learning and memory, has recently generated much interest. However, molecularly the D1-like receptors are comprised of at least two subtypes, namely D-1 and D-5, and it has not been possible to ascertain which of these two receptor classes is responsible for these functions due to the lack of selective ligands. In the present study, utilizing a combined antisense-in vivo dialysis approach, we show that the D-5 subtype is the dopamine D1-like receptor involved in modulating hippocampal acetylcholine (ACh) release, a transmitter implicated in a variety of cognitive processes. This is one of the first evidence for a functional role for the D-5 receptor.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2000

Olfactory bulbectomy alters NMDA receptor levels in the rat prefrontal cortex.

Olfactory bulbectomized (OBX) rats show a variety of behavioral and biochemical deficits that parallel human depression. We investigated the expression of glutamate receptor subtypes in cortical and subcortical brain regions following bilateral olfactory bulbectomy in adult rats. Quantitative receptor autoradiography using [(125)I]MK-801 (NMDA receptor), [(3)H]AMPA (AMPA receptor), and [(3)H]kainate (kainate receptor) was performed on brain sections at 1-5 weeks following olfactory bulbectomy. Our results show an elevation of NMDA receptors in the medial prefrontal cortex within 1 week following bulbectomy, which persisted up to at least 5 weeks post-bulbectomy. Neither kainate nor AMPA receptors were altered in any brain region examined. The potential significance of these results is discussed in light of experimental findings supporting a role for NMDA receptors in the mechanism of action of antidepressant drugs and the pathophysiology of major depression.

Animals↗

PubMed2000

Insulin-like growth factor-1 (IGF-1): a neuroprotective trophic factor acting via the Akt kinase pathway.

Insulin-like growth factor-I (IGF-I) is a pleiotropic polypeptide with a wide range of actions in both central and peripheral nervous sytems. Over the past few years, we studied the trophic as well as neuromodulatory roles of IGF-I in the brain. Accumulated evidence indicates that IGF-I, apart from regulating growth and development, protects neurons against cell death induced by amyloidogenic derivatives, glucose or serum deprivation via the activation of intracellular pathways implicating phosphatidylinositide 3/Akt kinase, winged-helix family of transcription factor FKHRL1 phosphorylation or production of free radicals. The effects of IGF-I on neuroprotection, glucose metabolism and activity-dependent plasticity suggest the potential usefulness of this growth factor or related mimetics in the treatment of Alzheimer's disease and other neurodegenerative disorders.

Alzheimer Disease↗

PubMed2000

Behavioral and neurochemical alterations following repeated phencyclidine administration in rats with neonatal ventral hippocampal lesions.

Exposure to chronic phencyclidine (PCP) has been reported to mimic certain aspects of schizophrenia in normal subjects as well as to exacerbate symptoms in schizophrenic patients. Analogous to schizophrenics, adult rats with neonatal ventral hippocampal (VH) lesions have been shown to display enhanced sensitivity to both stress and psychostimulants. In order to examine whether repeated PCP treatment can modulate behavior when administered to neonatal VH-lesioned animals, we examined locomotor activity and immobility time in the forced swimming test (FST) in neonatal VH-lesioned rats following repeated PCP treatment. Receptor autoradiography studies were also performed for dopamine (DA) and N-methyl-D-aspartate (NMDA) receptors to identify neurochemical correlates of the altered behavior in these animals. Though repeated PCP administration resulted in increased levels of locomotor activity and rearing in both VH-lesioned as well as sham rats, the effects were much more enhanced in the lesioned rats compared to sham. However, repeated PCP treatment induced hypolocomotion during the habituation period in both sham and lesioned rats. In the FST paradigm, lesioned rats displayed an altered retention of acquired immobility. Repeated PCP administration increased DA D1-like receptors in the caudate-putamen in lesioned rats and decreased striatal D2-like receptors in both sham and lesioned rats. Moreover, repeated PCP administration in lesioned rats decreased NMDA binding sites in the prefrontal cortex while increasing labelling in the subcortical regions. These results suggest that repeated administration of PCP can qualitatively and quantitatively affect behaviors in neonatal VH-lesioned rats related to abnormal neurodevelopmental processes presumably via prefrontal glutamatergic and subcortical dopaminergic dysfunctions.

Animals↗

PubMed2000

Rediscovering good old friend IGF-I in the new millenium: possible usefulness in Alzheimer's disease and stroke.

Much research has been done over the past two decades on the role of insulin-like growth factors I and II (IGF) in the maintenance of normal body homeostasis, especially in regard to various endocrine functions, growth and aging. For example, IGF-I is a well established promoter of tissue growth and has been used in the clinics for the treatment of growth related disorders, even being abused by athletes to enhance performance in competitions. In contrast, comparatively limited attention has been given to the potential significance of the IGFs in the central nervous system. Over the past few years, we have studied the trophic as well as neuromodulatory roles of the IGFs in the brain. IGF-I and IGF-II are potent modulators of acetylcholine release, IGF-I inhibiting release while IGF-II is a potent stimulant. Moreover, only the internalization of the IGF-I receptor complex was blocked by an inhibitor of phosphotyrosylation. This is in accordance with the differential nature of the IGF-I and IGF-II receptors, the former being a tyrosine kinase receptor while the later is a single transmembrane domain protein bearing binding sites for 6-mannose phosphate containing residues. The activation of IGF-I receptors protected neurons against cell death induced by amyloidogenic derivatives likely by an intracellular mechanism distinct from those involved in the regulation of acetylcholine release and neuronal growth. The stimulation of IGF-I receptors can activate intracellular pathways implicating a PI3/Akt kinase and CREB phosphorylation or modulate the production of free radicals. The effects, particularly those of IGF-I on key markers of the Alzheimer's (AD) brains namely cholinergic dysfunction, neuronal amyloid toxicity, tau phosphorylation and glucose metabolism suggest the potential usefulness of this growth factor in the treatment of neurodegenerative diseases. However, the poor bioavailability, enzymatic stability and brain penetration of IGF-I hamper progress in this regard. The recent development of a small, non-peptidyl mimetic of insulin able to directly activate the insulin receptor [Zhang, B., Salituro, G., Szalkowski, D., Li, Z., Zhang, Y., Royo, I., Vilella, D., Diez, M.T., Pelaez, F., Ruby, C., Kendall, R.L., Mao, X., Griffin, P., Calaycay, J., Zierath, J.R., Heck, J. V., Smith, R.G., Moller, D.E., 1999. Science, 284, 974-977] suggests that a similar strategy could be used for IGF-I and the IGF-I receptor leading to the characterization of IGF-I mimics of potential clinical usefulness.

Alzheimer Disease↗

PubMed2000

The molecular pharmacology of CGRP and related peptide receptor subtypes.

Calcitonin gene-related peptides (alpha and beta isoforms), better known as CGRPalpha and CGRPbeta, were isolated twenty years ago. In fact, these were the first peptides to be characterized using a molecular cloning strategy, which is not the traditional approach of biochemical extraction and purification. Paradoxically, progress in the characterization of CGRP receptor subtypes has been extremely slow as a result of difficulties in their cloning and the lack of selective receptor subtype agonists and antagonists. However, exciting progress has been made overthe pasttwo years and is briefly reviewed here.

Amino Acid Sequence↗

PubMed2000

Acetylcholine induces neuritic outgrowth in rat primary olfactory bulb cultures.

The rat olfactory bulb is innervated by basal forebrain cholinergic neurons and is endowed with both nicotinic and muscarinic receptors. The development of this centrifugal cholinergic innervation occurs mainly in early postnatal stages. This developmental time-course and the demonstration that acetylcholine can modulate some aspects of neuronal proliferation, differentiation or death, suggests the possible involvement of cholinergic afferents in the morphogenesis and/or plasticity of the olfactory bulb. The purpose of the present work was to assess whether acetylcholine could modulate neuronal morphogenesis in the olfactory bulb. Toward this aim, we developed a primary culture model of rat olfactory bulbs. Three major cell types were identified on the basis of their morphological and immunocytochemical phenotype: neuronal-shaped cells expressing the neuronal markers neuron specific enolase, microtubule associated protein 2, neural cell adhesion molecule and beta-tubulin III; glial-like cells immunoreactive for glial fibrillary acidic protein and flattened cells immunolabelled with antibodies against beta-tubulin III and nestin, most likely neuronal precursors. After three to six days of treatment with 100-microM carbachol, a cholinergic agonist, significant increase in neuritic length was observed in cultured olfactory bulb neurons. The neurite outgrowth effect of carbachol was abolished by co-treatment with 1 microM alpha-bungarotoxin, an alpha 7 subunit nicotinic receptor antagonist, but was not affected by the addition of 10 microM atropine, a general muscarinic antagonist. The effect of carbachol was also mimicked by the nicotinic agonists, nicotine (100 microM) and epibatidine (10 microM). This pharmacological profile suggested the involvement of nicotinic receptors of the alpha 7-like subtype as confirmed using 125I-alpha-bungarotoxin receptor autoradiography.Taken together, these data argue for a role for nicotinic receptors in neuritic outgrowth in the rat olfactory bulb and provide a cellular support to the previously described effects of acetylcholine on olfactory bulb plasticity in vivo.

Acetylcholine↗

PubMed2000

Decreased levels of neuropeptide Y(5) receptor binding sites in two experimental models of epilepsy.

It has been suggested that the anticonvulsant effects of neuropeptide Y (NPY) could be mediated by the activation of Y(2) and/or Y(5) receptors. NPY Y(1) receptor levels are known to decrease and Y(2) to increase in rat models of epilepsy. By using an autoradiographic approach, we investigated whether epilepsy models (kainic acid and kindling) are also associated with changes in Y(5) receptors. Compared with naive controls, [125I][Leu(31), Pro(34)]PYY/BIBP3226-insensitive (Y(5)) binding sites in the hippocampus (strata oriens and radiatum of CA3 and CA1) and in the neocortex (superficial layers) were unchanged in sham-stimulated rats, but reduced by approximately 50% in kindled rats (seven days after the last stimulus evokes seizure), and further reduced (to approximately -90%) 1h after a kindled seizure. Additionally, Y(5) receptor binding sites in the hippocampus and in the neocortex were unchanged 6h after kainic acid injection, but were highly reduced at 12 and 24h. No changes in Y(5) binding levels were found in the dentate gyrus and the pyramidal cell layer of the hippocampus. The present data suggest that changes in Y(5) receptor levels occur in epilepsy models. These changes may play a role in seizure expression and/or in the maintenance of kindling hyperexcitability.

Animals↗

PubMed2000

Morphine treatment induced calcitonin gene-related peptide and substance P increases in cultured dorsal root ganglion neurons.

The mechanism of spinal tolerance to the analgesic effects of opiates is unclear at present. We have reported previously that calcitonin gene-related peptide-like immunoreactivity was significantly increased in primary afferents of the spinal dorsal horn during the development of morphine tolerance, suggesting that changes in the level of pain-related neuropeptides in dorsal root ganglion neurons may be involved [Menard D. P. et al. (1996) J. Neurosci. 16, 2342-2351]. In this study, we investigated if in vitro treatment with morphine can mimic the in vivo findings and induce increases in calcitonin gene-related peptide-like immunostaining in cultured dorsal root ganglion neurons from young (three-month-old) and middle-aged (10-month-old) adult rats. Following a repetitive exposure to morphine sulfate (1, 5, 10 microM) for six days, the number of calcitonin gene-related peptide- and substance P-immunoreactive neurons in cultured dorsal root ganglia from three- and 10-month-old rats was significantly increased. A lower concentration (0.5 microM) of morphine induced these increases only in dorsal root ganglion neurons from middle-aged rats. Morphine treatment was also found to increase the number of calcitonin gene-related peptide-immunoreactive neurons possessing multiple, long branches (i.e. with at least one branch >0.5mm). This apparent increase in the number of calcitonin gene-related peptide- and substance P-immunoreactive neurons observed following morphine treatment was blocked by naloxone, an opiate antagonist, indicating the involvement of genuine opioid receptors. No significant change in the number of neuropeptide Y- or galanin-immunoreactive neurons in cultured dorsal root ganglia was detected following any of these treatments. These data suggest that repeated exposure to morphine rather selectively increases calcitonin gene-related peptide- and substance P-like immunoreactivity in cultured dorsal root ganglion neurons. Moreover, the sensitivity to morphine-induced changes is greater in cultured dorsal root ganglion neurons from 10- compared to three-month-old rats. Hence, cultured dorsal root ganglion neurons can provide a model to investigate the cellular and molecular mechanisms underlying alterations in neuropeptide levels following repeated exposure to opiates and their relevance to the development of opioid tolerance.

Age Factors↗

PubMed2000

Alteration of expression levels of neuronal nitric oxide synthase and haem oxygenase-2 messenger RNA in the hippocampi and cortices of young adult and aged cognitively unimpaired and impaired Long-Evans rats.

Neuronal nitric oxide synthase and haem oxygenase-2 are postulated to be important enzymes involved in neuronal transmission and modulation of free radical levels in neurons. Hippocampal and cortical neuronal nitric oxide synthase and haem oxygenase-2 expressions were compared in young adult (6 months) and aged (24-26 months) Long-Evans rats. Aged rats were assigned as either cognitively unimpaired or impaired based on their performances in the Morris water maze behavioural task. In situ hybridization revealed increased neuronal nitric oxide synthase messenger RNA levels in selected regions of the hippocampi and cortices of aged rats. Moreover, aged cognitively impaired animals showed significantly higher neuronal nitric oxide synthase messenger RNA expression than aged cognitively unimpaired animals in several brain regions. For haem oxygenase-2 mRNA expressions, both young and aged cognitively impaired rats showed increased expressions in hippocampi compared with aged cognitively unimpaired rats, while no difference was found in cortices between all three animal groups. The increase in neuronal nitric oxide synthase messenger RNA expression levels in the aged animals may be related to increased free radical production occurring in ageing. Alternatively, elevated neuronal nitric oxide synthase and haem oxygenase-2 messenger RNA expressions may represent compensatory responses to oxidative stress and age-related changes in neuronal functions. Regarding cognitive status, aged cognitively impaired rats showed significant spatial memory deficits relative to young and aged cognitively unimpaired rats. Our data suggest a correlation between age-related cognitive impairment and change in messenger RNA expressions for the neuronal nitric oxide synthase and haem oxygenase-2 systems in brain areas implicated in learning and memory processes.

Aging↗

PubMed2000

Increase in AMPA receptors in aged memory-impaired rats is not associated with increase in monoamine oxidase B levels.

Aged rats may be behaviorally classified as either cognitively impaired or unimpaired based upon their performance in the Morris water maze task. In aged Long-Evans rats, emergence of functional deficits has been related to the increase in the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subtype in most hippocampal subfields, not observed in other brain structures. As AMPA receptors expressed in astrocytes may participate in the delayed and long-term glial response to injury, we investigated whether astrocytes participate in the increase of AMPA receptor observed in these aged rats. To this end, distribution of monoamine oxidase B, used as an astroglial marker, was characterized by quantitative autoradiography in the hippocampus and septum of young adults (six months) and aged (24-25 months) rats using [3H]lazabemide. Specific binding to brain sections of young, aged unimpaired, and aged impaired animals were calculated densitometrically. Compared to young animals, all hippocampal subfields in the aged unimpaired group showed a significant age-related increased labeling, which was not present in the aged impaired group. This contrasts with the increased glial transcription described in this last group. We propose that increase in AMPA receptors in the aged memory-impaired animals may be related to an atypic astrocytic reactivity.

Aging↗

PubMed2000

Ontogenic profile of the expression of the mu opioid receptor gene in the rat telencephalon and diencephalon: an in situ hybridization study.

The developmental profile of mu (mu) opioid receptor gene expression has been characterized in the embryonic, postnatal and adult rat brain by in situ hybridization histochemistry. By ED12, mu opioid receptor mRNA was detectable in the deep neuroepithelium of the cortical plate. In the developing rat central nervous system (ED13-PD40), transcripts were seen over numerous telencephalic and diencephalic structures, such as the olfactory bulb, caudate-putamen, nucleus accumbens, amygdaloid complex, hippocampal formation, hypothalamus and thalamus. In the vast majority of brain regions examined, the developmental profile of the mu opioid receptor gene expression is similar to that of its translated protein as established using receptor autoradiography. Once a hybridization signal is detected in the prenatal period, it gradually increased to reach maximal levels during the second and third postnatal weeks. By the end of the third postnatal week, mu opioid receptor mRNA levels decreased to reach amounts seen in adulthood. Our study demonstrates that mu opioid receptor gene expression is seen very early on in the embryonic rat brain with transient increases observed during the critical period of neurogenesis, neuronal migration and synaptogenesis, suggesting a role of this opioid receptor subtype in brain developmental processes.

Animals↗