RESUMO
BACKGROUND: Fetal alcohol spectrum disorder (FASD) is one of the leading causes of neurodevelopmental disorder for which there is a pressing need for an effective treatment. Recent studies have investigated the essential nutrient choline as a postnatal treatment option. Supplementation with choline has produced improvements in behavioral tasks related to learning and memory and reverted changes in methylation signature following third-trimester equivalent ethanol exposure. We examined whether there are related improvements in hippocampal synaptic plasticity in vivo. METHODS: Sprague-Dawley offspring were administered binge-levels of ethanol from postnatal day (PND) 4 to 9, then treated with choline chloride (100 mg/kg/day) from PND 10 to 30. In vivo electrophysiology was performed on male and female offspring from PND 55 to 70. Long-term potentiation (LTP) was induced in the medial perforant pathway of the dentate gyrus using a theta-burst stimulation (TBS) protocol, and field-evoked postsynaptic potentials (EPSPs) were evoked for 60 min following the conditioning stimulus. RESULTS: Developmental ethanol exposure caused long-lasting deficits in LTP of the slope of the evoked responses and in the amplitude of the population spike potentiation. Neither deficit was rescued by postnatal choline supplementation. CONCLUSIONS: In contrast to our prior findings that choline can improve hippocampal plasticity (Nutrients, 2022, 14, 2004), here we found that deficits in hippocampal synaptic plasticity due to developmental ethanol exposure persisted into adulthood despite adolescent choline supplementation. Future research should examine more subtle changes in synaptic plasticity to identify synaptic changes that mirror behavioral improvements.
RESUMO
Cannabis use has risen dramatically in recent years due to global decriminalization and a resurgence in the interest of potential therapeutic benefits. While emerging research is shaping our understanding of the benefits and harms of cannabis, there remains a paucity of data specifically focused on how cannabis affects the female population. The female experience of cannabis use is unique, both in the societal context and because of the biological ramifications. This is increasingly important given the rise in cannabis potency, as well as the implications this has for the prevalence of Cannabis Use Disorder (CUD). Therefore, this scoping review aims to discuss the prevalence of cannabis use and CUD in women throughout their lifespan and provide a balanced prospective on the positive and negative consequences of cannabis use. In doing so, this review will highlight the necessity for continued research that goes beyond sex differences.
Assuntos
Cannabis , Abuso de Maconha , Humanos , Feminino , Masculino , Cannabis/efeitos adversos , Abuso de Maconha/epidemiologia , LongevidadeRESUMO
Hippocampal slices are widely used for in vitro electrophysiological experiments to study underlying mechanisms for synaptic transmission and plasticity, and there is a growing appreciation for sex differences in synaptic plasticity. To date, several studies have shown that the process of making slices from male animals can induce synaptogenesis in cornu ammonis area 1 (CA1) pyramidal cells, but there is a paucity of data for females and other brain regions. In the current study we use microcrystals of the lipophilic carbocyanine dye DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) to stain individual neurons in the CA1 and dentate gyrus (DG) hippocampal subfields of postnatal day 21 male and female rats. We show that the preparation of sections for electrophysiology produces significant increases in spines in sections obtained from females, similar to that observed in males. We also show that the procedures used for in vitro electrophysiology also result in significant spine increases in the DG and CA1 subfields. These results demonstrate the utility of this refined DiI procedure for staining neuronal dendrites and spines. They also show, for the first time, that in vitro electrophysiology slice preparations enhance spine numbers on hippocampal cells equivalently in both juvenile females and males.NEW & NOTEWORTHY This study introduces a new DiI technique that elucidates differences in spine numbers in juvenile female and male hippocampus, and shows that slice preparations for hippocampal electrophysiology in vitro may mask these differences.
Assuntos
Região CA1 Hipocampal/citologia , Carbocianinas , Espinhas Dendríticas , Giro Denteado/citologia , Eletrofisiologia/métodos , Corantes Fluorescentes , Caracteres Sexuais , Coloração e Rotulagem/métodos , Animais , Feminino , Masculino , RatosRESUMO
Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability, and is the leading known single-gene cause of autism spectrum disorder. FXS patients display varied behavioural deficits that include mild to severe cognitive impairments in addition to mood disorders. Currently there is no cure for this condition, however minocycline is becoming commonly prescribed as a treatment for FXS patients. Minocycline has been reported to alleviate social behavioural deficits, and improve verbal functioning in patients with FXS; however, its mode of action is not well understood. Previously we have shown that FXS results in learning impairments that involve deficits in N-methyl-d-aspartate (NMDA) receptor-dependent synaptic plasticity in the hippocampal dentate gyrus (DG). Here we tested whether chronic treatment with minocycline can improve these deficits by enhancing NMDA receptor-dependent functional and structural plasticity in the DG. Minocycline treatment resulted in a significant enhancement in NMDA receptor function in the dentate granule cells. This was accompanied by an increase in PSD-95 and GluN2A and GluN2B subunits in hippocampal synaptoneurosome fractions. Minocycline treatment also enhanced dentate granule cell dendritic length and branching. In addition, our results show that chronic minocycline treatment can rescue performance in novel object recognition in FXS mice. These findings indicate that minocycline treatment has both structural and functional benefits for hippocampal cells, which may partly contribute to the pro-cognitive effects minocycline appears to have for treating FXS.
Assuntos
Proteína do X Frágil da Deficiência Intelectual/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Minociclina/administração & dosagem , Neurônios/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Animais , Esquema de Medicação , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/patologia , Técnicas de Cultura de Órgãos , Resultado do TratamentoRESUMO
Fragile-X syndrome (FXS) is caused by the transcriptional repression of the Fmr1 gene resulting in loss of the Fragile-X mental retardation protein (FMRP). This leads to cognitive impairment in both male and female patients, however few studies have focused on the impact of FXS in females. Significant cognitive impairment has been reported in approximately 35% of women who exhibit a heterozygous Fmr1 gene mutation, however to date there is a paucity of information regarding the mechanistic underpinnings of these deficits. We, and others, have recently reported that there is significant impairment in N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal dentate gyrus (DG) of male Fmr1 knock out mice. Here we examined if female mice displaying a heterozygous loss of the Fmr1 gene (Fmr1+/-) would exhibit similar impairments in DG-dependent spatial memory processing and NMDAR hypofunction. We found that Female Fmr1+/- mice did not show impaired metabotropic glutamate receptor (mGluR)-LTD in the CA1 region, and could perform well on a temporal ordering task that is thought to involve this brain region. In contrast, female Fmr1+/- mice showed impairments in a pattern separation task thought to involve the DG, and also displayed a significant impairment in both NMDAR-dependent LTD and LTP in this region. The LTP impairment could be rescued by administering the NMDAR co-agonist, glycine. Our data suggests that NMDAR hypofunction in the DG may partly contribute to learning and memory impairment in female Fmr1+/- mice. Targeting NMDAR-dependent mechanisms may offer hope as a new therapeutic approach for treating female FXS patients with learning and memory impairments.
Assuntos
Giro Denteado/patologia , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Síndrome do Cromossomo X Frágil/patologia , Plasticidade Neuronal/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Modelos Animais de Doenças , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/genética , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/tratamento farmacológico , Síndrome do Cromossomo X Frágil/genética , Genótipo , Glicina/uso terapêutico , Elevação dos Membros Posteriores , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Comportamento Espacial/efeitos dos fármacos , Comportamento Espacial/fisiologia , Natação/psicologia , Valina/análogos & derivados , Valina/farmacologia , Valina/uso terapêuticoRESUMO
The fragile X mental retardation protein (FMRP) is an important regulator of protein translation, and a lack of FMRP expression leads to a cognitive disorder known as fragile X syndrome (FXS). Clinical symptoms characterizing FXS include learning impairments and heightened anxiety in response to stressful situations. Here, we report that, in response to acute stress, mice lacking FMRP show a faster elevation of corticosterone and a more immediate impairment in N-methyl-d-aspartate receptor (NMDAR) dependent long-term potentiation (LTP) in the dentate gyrus (DG). These stress-induced LTP impairments were rescued by administering the glucocorticoid receptor (GR) antagonist RU38486. Administration of RU38486 also enhanced LTP in Fmr1(-/y) mice in the absence of acute stress to wild-type levels, and this enhancement was blocked by application of the NMDAR antagonist 2-amino-5-phosphonopentanoic acid. These results suggest that a loss of FMPR results in enhanced GR signaling that may adversely affect NMDAR dependent synaptic plasticity in the DG.
Assuntos
Corticosteroides/sangue , Giro Denteado/metabolismo , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Plasticidade Neuronal/genética , Transdução de Sinais/genética , Animais , Estimulação Elétrica , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/genética , Proteína do X Frágil da Deficiência Intelectual/genética , Antagonistas de Hormônios/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mifepristona/uso terapêutico , Plasticidade Neuronal/efeitos dos fármacos , Técnicas de Patch-Clamp , Restrição Física/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/etiologia , Fatores de Tempo , Valina/análogos & derivados , Valina/farmacologiaRESUMO
Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and results from a loss of Fragile X mental retardation protein (FMRP). FMRP is important for mRNA shuttling and translational control and binds to proteins important for synaptic plasticity. Like many developmental disorders, FXS is associated with alterations in synaptic plasticity that may impair learning and memory processes in the brain. However, it remains unclear whether FMRP plays a ubiquitous role in synaptic plasticity in all brain regions. We report that a loss of FMRP leads to impairments in N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity in the dentate gyrus (DG), but not in the cornu ammonis area 1 (CA1) subregion of the hippocampus of adult mice. DG-specific deficits are accompanied by a significant reduction in NMDAR GluN1, GluN2A, and GluN2B subunit levels and reduced serine 831 GluA1 phosphorylation specifically in this region. Importantly, we demonstrate that treatment with NMDAR co-agonists (glycine or D-serine) independently rescue impairments in NMDAR-dependent synaptic plasticity in the DG of the Fragile X mental retardation 1 (Fmr1) knockout mouse. These findings implicate the NMDAR in the pathophysiology of FXS and suggest that indirect agonists of the NMDAR may be a successful therapeutic intervention in FXS.
Assuntos
Proteína do X Frágil da Deficiência Intelectual/genética , Hipocampo/metabolismo , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/genética , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/metabolismo , Glicina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/metabolismo , Serina/farmacologiaRESUMO
Exposure to ethanol in utero is associated with a myriad of sequelae for the offspring. Some of these effects are morphological in nature and noticeable from birth, while others involve more subtle changes to the brain that only become apparent later in life when the individuals are challenged cognitively. One brain structure that shows both functional and structural deficits following prenatal ethanol exposure is the hippocampus. The hippocampus is composed of two interlocking gyri, the cornu ammonis (CA) and the dentate gyrus (DG), and they are differentially affected by prenatal ethanol exposure. The CA shows a more consistent loss in neuronal numbers, with different ethanol exposure paradigms, than the DG, which in contrast shows more pronounced and consistent deficits in synaptic plasticity. In this study we show that significant deficits in adult hippocampal neurogenesis are apparent in aged animals following prenatal ethanol exposure. Deficits in hippocampal neurogenesis were not apparent in younger animals. Surprisingly, even when ethanol exposure occurred in conjunction with maternal stress, deficits in neurogenesis did not occur at this young age, suggesting that the capacity for neurogenesis is highly conserved early in life. These findings are unique in that they demonstrate for the first time that deficits in neurogenesis associated with prenatal ethanol consumption appear later in life.
Assuntos
Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiopatologia , Neurogênese/fisiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Estresse Psicológico/fisiopatologia , Animais , Depressores do Sistema Nervoso Central/sangue , Depressores do Sistema Nervoso Central/toxicidade , Etanol/sangue , Etanol/toxicidade , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Gravidez , Ratos Sprague-Dawley , Restrição Física , Caracteres SexuaisRESUMO
Alcohol consumption during pregnancy is deleterious to the developing brain of the fetus and leads to persistent deficits in adulthood. Long-term potentiation (LTP) is a biological model for learning and memory processes and previous evidence has shown that prenatal ethanol exposure (PNEE) affects LTP in a sex specific manner during adolescence. The objective of this study was to determine if there are sex specific differences in adult animals and to elucidate the underlying molecular mechanisms that contribute to these differences. Pregnant Sprague-Dawley dams were assigned to either; liquid ethanol, pair-fed or standard chow diet. In vivo electrophysiology was performed in the hippocampal dentate gyrus (DG) of adult offspring. LTP was induced by administering 400 Hz stimuli. Western blot analysis for glutamine synthetase (GS) and glutamate decarboxylase from tissue of the DG indicated that GS expression was increased following PNEE. Surprisingly, adult females did not show any deficit in N-methyl-D-aspartate (NMDA)-dependent LTP after PNEE. In contrast, males showed a 40% reduction in LTP. It was indicated that glutamine synthetase expression was increased in PNEE females, suggesting that altered excitatory neurotransmitter replenishment may serve as a compensatory mechanism. Ovariectomizing females did not influence LTP in control or PNEE animals, suggesting that circulating estradiol levels do not play a major role in maintaining LTP levels in PNEE females. These results demonstrate the sexually dimorphic effects of PNEE on the ability for the adult brain to elicit LTP in the DG. The mechanisms for these effects are not fully understood, but an increase in glutamine synthetase in females may underlie this phenomenon.
Assuntos
Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Caracteres Sexuais , Animais , Western Blotting , Eletrofisiologia , Feminino , Glutamato Descarboxilase/biossíntese , Glutamato-Amônia Ligase/biossíntese , Hipocampo/enzimologia , Hipocampo/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Sprague-DawleyRESUMO
Neurogenesis continues to occur in restricted regions of the brain throughout adulthood and can be modulated by dietary factors. Liquid or "soft" diets are commonly used for the administration of drugs in experimental models of disease, making it critical to determine whether dietary composition itself can affect neurogenesis. In this study Sprague-Dawley rats were fed either a liquid or a solid diet of identical composition from weaning until young adulthood. No differences in neuronal differentiation and survival of newly born cells were observed between rats that were fed a liquid diet and those that received a solid diet. However, a significant reduction in hippocampal cell proliferation was observed in the liquid diet-fed group, as assessed by the expression of two endogenous proliferation markers, Ki67 and proliferating cell nuclear antigen (PCNA). The method of feeding did not alter the basal function of the hypothalamic-pituitary-adrenal (HPA) axis in these animals, as no changes in circulating levels of corticosterone (CORT) were detected between liquid and solid diet-fed groups. There was also a significant reduction in cellular proliferation in the hypothalamus of liquid diet-fed rats, a brain region known to be involved in feeding-related behaviors. These findings indicate that liquid diets themselves can directly impact rates of cellular proliferation, but this does not seem to impact levels of overall neurogenesis in the adult brain.
Assuntos
Proliferação de Células , Alimentos Formulados/efeitos adversos , Hipocampo/citologia , Hipocampo/fisiologia , Neurogênese/fisiologia , Fatores Etários , Animais , Proteína Duplacortina , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
The medial perforant path (MPP) and lateral perforant path (LPP) inputs to the hippocampal dentate gyrus form two distinct laminar inputs onto the middle and distal aspects of granule cell dendrites. Previous evidence indicated that paired stimuli reliably produced paired-pulse depression (PPD) in the MPP and paired-pulse facilitation (PPF) in the LPP. Despite this, several years of practical experience in our laboratory questioned the utility of using paired-pulse administration to reliably differentiate the MPP and LPP in vitro. Using visualized field and whole-cell recordings in male Sprague-Dawley rats, we demonstrate that both pathways show net PPF of the excitatory postsynaptic potential (fEPSP) at 50-ms interpulse intervals. LPP afferents did reliably exhibit greater PPF than MPP afferents. Thus, the LPP reliably exhibits a greater paired-pulse ratio than the MPP. The magnitude of the paired-pulse ratio was reduced in both afferents by raising calcium levels or lowering the temperature of the recording chamber. PPD of MPP-evoked fEPSPs was only reliably detected at moderate to high stimulus intensities when population spike activity was evident. PPD was more evident in whole cell voltage clamp recordings but nonetheless was not completely diagnostic as PPD was occasionally observed with LPP stimulation as well. We found the MPP and LPP could be reliably identified using conventional microscopy with hippocampal slices, and that they could be distinguished through the analysis of evoked waveform kinetics. This work refines our knowledge of electrophysiological differences between MPP and LPP projections and will help to facilitate the selective activation of these pathways.
Assuntos
Giro Denteado/fisiologia , Via Perfurante/fisiologia , Animais , Giro Denteado/citologia , Eletrofisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Masculino , Plasticidade Neuronal/fisiologia , Técnicas de Patch-Clamp , Via Perfurante/citologia , Ratos , Ratos Sprague-DawleyRESUMO
The hippocampus is a dynamic brain structure involved with learning and memory. Long-term potentiation (LTP) is a neuronal model of learning and memory and, in adult rodents, is enhanced by voluntary exercise (VEx). The current study sought to elucidate whether synaptic plasticity in the male and female adolescent hippocampus is augmented by VEx. Consistent with previous studies, VEx significantly enhanced LTP in adolescent males following weak and strong theta-burst stimulation. Despite running the same amount as males, however, VEx did not enhance LTP in females above non-runner females. Surprisingly, the exercise-induced enhancement to LTP in males was seen in the absence of a change in brain derived neurotrophic factor in the dentate gyrus (DG). These findings indicate that adolescent males and females are differentially sensitive to the potentiating effect of exercise on hippocampal synaptic plasticity.
Assuntos
Giro Denteado/fisiologia , Potenciação de Longa Duração/fisiologia , Condicionamento Físico Animal/métodos , Animais , Biofísica , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Estimulação Elétrica/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Regulação da Expressão Gênica/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Fatores SexuaisRESUMO
Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the selective loss of the expression of the Fmr1 gene. Key symptoms in FXS include intellectual impairment and abnormal anxiety-related behaviors. Fmr1 knockout (KO) mice exhibited reduced anxiety on two behavioral tests as well as a blunted corticosterone response to acute stress. Spatial learning and memory was not impaired when tested with both the classic Morris water and Plus-shaped mazes. Adult hippocampal neurogenesis has been associated with spatial learning and memory and emotions such as anxiety and depression. The process of neurogenesis appears abnormal in young adult Fmr1 KO mice, with significantly fewer bromodeoxyuridine-positive cells surviving for at least 4 weeks in the ventral subregion of the dentate gyrus (DG), a hippocampal subregion more closely associated with emotion than the dorsal DG. Within this smaller pool of surviving cells, we observed a concomitant increase in the proportion of surviving cells that acquire a neuronal phenotype. We did not observe a clear difference in cell proliferation using both endogenous and exogenous markers. This work indicates that loss of Fmr1 expression can alter anxiety-related behaviors in mice as well as produce region-specific alterations in hippocampal adult neurogenesis.
Assuntos
Ansiedade/genética , Ansiedade/patologia , Giro Denteado/patologia , Giro Denteado/fisiologia , Proteína do X Frágil da Deficiência Intelectual/genética , Neurogênese/genética , Animais , Ansiedade/fisiopatologia , Sobrevivência Celular/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
The spontaneous or targeted deletion of the nuclear receptor transcription factor Nr2e1 produces a mouse that shows hypoplasia of the hippocampal formation and reduced neurogenesis in adult mice. In these studies we show that hippocampal synaptic transmission appears normal in the dentate gyrus and cornu ammonis 1 subfields of adult mice that lack Nr2e1 (Nr2e1-/-), and that fEPSP shape, paired-pulse responses, and short-term plasticity are not substantially altered in either subfield. In contrast, the expression of long-term potentiation is selectively impaired in the dentate gyrus, and not in the cornu ammonis 1 subfield. Golgi analysis revealed that there was a significant reduction in both dendritic branching and dendritic length that was specific to dentate gyrus granule cells in the Nr2e1-/- mice. These results indicate that Nr2e1 deletion can significantly alter both synaptic plasticity and dendritic structure in the dentate gyrus.
Assuntos
Dendritos/fisiologia , Giro Denteado/fisiologia , Plasticidade Neuronal/fisiologia , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/fisiologia , Sinapses/fisiologia , Animais , Dendritos/ultraestrutura , Giro Denteado/citologia , Giro Denteado/ultraestrutura , Estimulação Elétrica , Eletrodos Implantados , Eletrofisiologia , Feminino , Genótipo , Histocitoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sinapses/ultraestrutura , Transmissão Sináptica/genética , Transmissão Sináptica/fisiologiaRESUMO
Neurogenesis is a constitutive activity in the adult dentate gyrus whereby new cells are created in the subgranular zone, before becoming neurons in the dentate gyrus granule cell layer. New granule cells are thought to migrate from the subgranular zone outwards to the edge of the cell layer as they mature. In these experiments we examined the dendritic morphology of granule cells in the subgranular zone, and the inner and outer regions of the granule cell zone in Sprague-Dawley rats with low and high rates of neurogenesis. In animals with lower rates of neurogenesis, the number of primary dendrites, degree of dendritic complexity and total dendritic length was lowest in cells located in the subgranular zone, higher in inner granule cell zone neurons, and highest in outer granule cell zone granule cells. Subgranular zone granule cells typically extended one primary dendrite and had a simple, immature dendritic tree, while granule cells in the outer granule cell zone had an increased number of primary dendrites, greater dendritic complexity, and greater total dendritic length. Animals that engaged in voluntary exercise showed increased neurogenesis, and the proportion of cells with one or two primary dendrites was increased in all of the granule cell zones. Despite having fewer primary processes, these cells showed enhanced dendritic complexity and an overall increase in their total dendritic length. These results indicate that granule cell dendritic morphology may be indicative of the age and position of a cell in the granule cell layer, but that in animals with increased rates of neurogenesis, the proportion of cells exhibiting what is considered an immature phenotype is increased throughout the all regions of the dentate gyrus cell layer.
Assuntos
Dendritos/ultraestrutura , Giro Denteado/anatomia & histologia , Animais , Divisão Celular/fisiologia , Grânulos Citoplasmáticos/ultraestrutura , Giro Denteado/citologia , Complexo de Golgi/ultraestrutura , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Nestin is a putative neural stem cell marker that is expressed in different areas of the adult mammalian brain that are known to support mitotic activity. Recently the neocortex has been proposed to support neurogenesis, however little is known of the expression pattern of nestin in neocortex. In the present study, we demonstrate that cells that express nestin can be found throughout the neocortex, and that these cells are morphologically heterogeneous. Some nestin-expressing cells had one extension arising from the cell body, reminiscent of the nestin-expressing cells that are thought to be young neurons in the hippocampus. The frequency of single extension cells in the neocortex was approximately one cell per 50,000 microm(2). Other cells had numerous extensions arising from the cell body. In all cases, cells that expressed nestin were also found to co-label with the glial marker glial fibrillary acidic protein. In addition, nestin-expressing cells in the neocortex did not express the cell cycle marker, Ki-67, indicating they were not actively engaged in mitotic activity. When small lesions were made in cortex, nestin could also be observed in reactive astrocytes as part of the inflammatory response. Approximately 94% of reactive astrocytes expressed Ki-67. These results demonstrate that there are different populations of cells in the neocortex that can express nestin, but that only reactive astrocytes in this region are mitotically active.
Assuntos
Proteínas de Filamentos Intermediários/biossíntese , Neocórtex/citologia , Neocórtex/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Neurônios/metabolismo , Células-Tronco/metabolismo , Animais , Astrócitos/metabolismo , Contagem de Células , Imuno-Histoquímica , Masculino , Mitose/fisiologia , Nestina , Ratos , Ratos Sprague-DawleyRESUMO
The culturable component of bacterial communities found in the endoroot and associated exoroot (root zone soil) was examined in potatoes (Solanum tuberosum L.) grown under either conventional or minimum tillage systems. Bacterial species--abundance relationships were determined and in vitro antibiosis ability investigated to discover whether tillage practice or bacteria source (endo- or exoroot) influenced bacterial community structure and functional versatility. Antibiosis abilities against Phytophthora erythroseptica Pethyb. (causal agent of pink rot of potatoes), Streptomyces scabies (Thaxt.) Waksm. and Henrici) (causal agent of potato common scab), and Fusarium oxysporum Schlecht. Emend. Snyder and Hansen (causal agent of fusarium potato wilt) were selected as indicators of functional versatility. Bacterial community species richness and diversity indices were significantly greater (P = 0.001) in the exoroot than in the endoroot. While both endo- and exoroot communities possessed antibiosis ability against the phytopathogens tested, a significantly greater proportion (P = 0.0001) of the endoroot population demonstrated antibiosis ability than its exoroot counterpart against P. erythroseptica and F. oxysporum. Tillage regime had no significant influence on species-abundance relationships in the endo- or exoroot but did influence the relative antibiosis ability of bacteria in in vitro challenges against S. scabies, where bacteria sourced from minimum tillage systems were more likely to have antibiosis ability (P = 0.0151). We postulate that the difference in the frequency of isolates with antibiosis ability among endoroot versus exoroot populations points to the adaptation of endophytic bacterial communities that favour plant host defence against pathogens that attack the host systemically.
Assuntos
Antibiose , Bactérias/crescimento & desenvolvimento , Fusarium/crescimento & desenvolvimento , Phytophthora/crescimento & desenvolvimento , Tubérculos/microbiologia , Solanum tuberosum/microbiologia , Streptomyces/crescimento & desenvolvimento , Agricultura/métodos , Bactérias/classificação , Bactérias/isolamento & purificação , Ecossistema , Doenças das Plantas/microbiologiaRESUMO
Corticotrophin-releasing hormone is a key regulator of the mammalian stress response. Although its actions on behavior are well documented, the actions of corticotrophin-releasing hormone in cortical neuronal systems are poorly understood. In the present experiments, adult male Sprague-Dawley rats were anesthetized and field excitatory post-synaptic potential recordings were made from sensorimotor cortex layer II/III and layer V cells. Infusions of corticotrophin-releasing hormone (100 ng/nl) directly into the sensorimotor cortex produced a significant depression of the initial excitatory component of evoked responses that could be prevented by prior administration of a corticotrophin-releasing hormone antagonist. Although requiring the activation of corticotrophin-releasing hormone receptors, the depression was also dependent upon N-methyl-D-aspartate receptor activity and could be blocked by the competitive N-methyl-D-aspartate antagonist -3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonate. These findings demonstrate that corticotrophin-releasing hormone has a novel depressant-like action in sensorimotor cortex in vivo that may play a role in modulating motor activity during periods of stress.
Assuntos
Hormônio Liberador da Corticotropina/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Córtex Motor/citologia , Neurônios/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Interações Medicamentosas , Estimulação Elétrica/métodos , Eletrofisiologia/métodos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Depressão Sináptica de Longo Prazo/fisiologia , Depressão Sináptica de Longo Prazo/efeitos da radiação , Masculino , Piperazinas/farmacologia , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
We have previously shown that voluntary exercise produces enhanced neurogenesis and long-term potentiation (LTP) in the dentate gyrus (DG) of mice in vitro. In the present experiments we show that rats given access to a running wheel (Runners) exhibit significantly more short-term potentiation and LTP with theta-patterned conditioning stimulation in vivo than do age-matched litter mates (Controls). This increase in LTP appears to reflect an alteration in the induction threshold for synaptic plasticity that accompanies voluntary exercise. Weak theta-patterned stimulation, which did not produce LTP in control subjects, produced a robust and long-lasting LTP in Runners. LTP induction in both groups was dependent upon the activation of N-methyl-D-aspartate (NMDA) receptors, and could be blocked by the competitive antagonist [+/-]-3-[2-carboxypiperazin-4-yl] propanephosphonic acid. Consistent with these findings, we found that mRNA levels for NR2B subtype of NMDA receptor were increased specifically in the DG of Runners. In addition to changes in NR2B mRNA levels, quantitative polymerase chain reaction analysis revealed that brain-derived neurotrophic factor (BDNF) and glutamate receptor 5 mRNA levels were also significantly elevated in the DG of Runners, but not in other areas of the hippocampus. Thus, alterations in the expression of BDNF, and specific glutamate receptor subtypes, may underlie the ability of exercise to enhance neurogenesis and reduce the threshold for LTP in the DG.
Assuntos
Giro Denteado/citologia , Giro Denteado/fisiologia , Potenciação de Longa Duração/fisiologia , Plasticidade Neuronal/fisiologia , Condicionamento Físico Animal/fisiologia , Fatores Etários , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Contagem de Células , Divisão Celular/fisiologia , Estimulação Elétrica , Expressão Gênica/fisiologia , Masculino , Neurônios/citologia , Neurônios/fisiologia , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Receptores de Ácido Caínico/genética , Receptores de N-Metil-D-Aspartato/genética , Corrida/fisiologia , VoliçãoRESUMO
The ionotropic glutamate receptor subunit GluR6 undergoes developmentally and regionally regulated Q/R site RNA editing that reduces the calcium permeability of GluR6-containing kainate receptors. To investigate the functional significance of this editing in vivo, we engineered mice deficient in GluR6 Q/R site editing. In these mutant mice but not in wild types, NMDA receptor-independent long-term potentiation (LTP) could be induced at the medial perforant path-dentate gyrus synapse. This indicates that kainate receptors with unedited GluR6 subunits can mediate LTP. Behavioral analyses revealed no differences from wild types, but mutant mice were more vulnerable to kainate-induced seizures. Together, these results suggest that GluR6 Q/R site RNA editing may modulate synaptic plasticity and seizure vulnerability.