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At least 865 records · Page 48Linked to original sources

PubMed1997

Amygdala kindling alters N-methyl-D-aspartate receptor subunit messenger RNA expression in the rat supraoptic nucleus.

Intense electrical activity throughout the brain which results from generalized epileptic or kindled seizures is thought to cause persistent and widespread neuronal plastic changes. We have previously reported that stage 5 kindled seizures cause an increase in vasopressin messenger RNA content and nitric oxide synthase activity in neuroendocrine cells of the supraoptic nucleus which lasts for at least four months after the last seizure. To evaluate whether changes in the expression of N-methyl-D-aspartate receptor subunits might contribute to these effects, the expression of NR1, NR2A, NR2B. NR2C and NR2D subunit messenger RNAs was examined by in situ hybridization in neuroendocrine cells of the supraoptic nucleus one month after amygdala kindling to stage 5 seizures. No change in NR1 subunit messenger RNA expression was seen. In contrast, NR2B subunit messenger RNA was significantly increased. by about 63%, and NR2D subunit messenger RNA was significantly decreased, by about 22%. indicating a shift in NR2 subunit messenger RNA expression. NR2B subunit messenger RNA was also significantly increased in adjacent limbic structures. The long-lasting shift towards increased NR2B and decreased NR2D messenger RNA expression after kindling suggests that N-methyl-D-aspartate receptor NR2 composition may be an important factor in the maintenance of pathological plasticity following generalized seizures. If these changes in messenger RNA are translated into increased NR2B and decreased NR2D subunits in the N-methyl-D-aspartate receptors in vivo, both a decrease in sensitivity due to a strong magnesium block and an increase in channel ion gating might be predicted.

Amygdala↗

PubMed2004

[Neuropsychological equivalences and therapeutic consequences of the dynamic structural model].

Firstly the core concepts of the dynamic structural model and the methods from which the model was developed will be discussed. These core concepts include concepts of personality structure and affect dynamic, of dynamic affective derailment with dissociation of individual element structures, the capacity of disactualisation of unwanted mental content, and autopraxis as the basis of memory renewals, which are formed and channelled through selection. Furthermore we will consider the dependence of memory function on texturing, development of coherence, affective freighting and repetition of usage in Janzarik's system. Neuropsychological counterparts are to be found in experimental studies on filter, gating and control functions, in studies on automatic vs. controlled processes, the central executive and executive control function. Autopraxis and priming operations will be related to each other. Furthermore, the connection of neuronal plasticity to a raised signal-to-noise ratio and the relationship to extinction of delusional content through broadening of new fields of experience will be discussed. In a summary of the frappant parallels of experimental and clinical viewpoints of Janzarik's model we will show the therapeutic perspective and the psychotherapeutically important integration of the lifeworld of the patient with experimentally investigated neuropsychological functions through Janzarik's conceptualisation.

Humans↗

PubMed1998

The disconnection hypothesis.

This article reviews the disconnection hypothesis of schizophrenia and presents a mechanistic account of how dysfunctional integration among neuronal systems might arise. This neurobiological account is based on the central role played by neuronal plasticity in shaping the connections and the ensuing dynamics that underlie brain function. The particular hypothesis put forward here is that the pathophysiology of schizophrenia is expressed at the level of modulation of associative changes in synaptic efficacy; specifically the modulation of plasticity in those brain systems responsible for emotional learning and memory, in the post-natal period. This modulation is mediated by ascending neurotransmitter systems that: (i) have been implicated in schizophrenia; and (ii) are known to be involved in consolidating synaptic connections during learning. The proposed pathophysiology would translate, in functional terms, into a disruption of the reinforcement of adaptive behaviour that is consistent with the disintegrative aspects of schizophrenic neuropsychology.

Brain↗

PubMed2005

Glutamate modulators as novel interventions for mood disorders.

UNLABELLED: Recent evidence suggests that critical molecules in neurotrophic signaling cascades are long-term targets for currently available monoaminergic antidepressants. As chronic and severe mood disorders are characterized by impairments in neuronal resilience, pharmacological strategies that subserve a neuroprotective function might alter disorder pathophysiology and modify disease progression. Several promising approaches involve modulation of the glutamate neurotransmitter system, via post-synaptic receptor blockade or potentiation and presynaptic vesicular release inhibition. A focused review of the extant scientific literature was conducted, with a discussion of 3 compounds or classes of drugs currently undergoing clinical investigation: ketamine, riluzole, and AMPA receptor potentiators. Recent investigations in mood disordered patients suggest that the NMDA receptor antagonist ketamine might demonstrate rapid antidepressant properties. Riluzole has been shown to reverse glutamate-mediated impairments in neuronal plasticity and to stimulate the synthesis of brain derived neurotrophic factor. Open-label trials in treatment-resistant depression have yielded promising results. Likewise, AMPA receptor potentiators favorably impact neurotrophic factors as well as enhance cognition. CONCLUSIONS: Pharmacological approaches that modulate components of the glutamate system offer novel targets for severe, recurrent mood disorders. Controlled studies are necessary.

Animals↗

PubMed1985

Synaptic amplification by active membrane in dendritic spines.

The suspected functional role of dendritic spines as loci of neuronal plasticity (possibly memory and learning) is greatly enriched when active membrane properties are assumed at the spine head. Computations with reasonable electrical and structural parameter values (corresponding to an optimal range for spine stem resistance) show that an active spine head membrane can provide very significant synaptic amplification and also strongly non-linear properties that could modulate the integration of input from many afferent sources.

Cell Membrane↗

PubMed1999

Memory restoring and neuroprotective effects of the proline-containing dipeptide, GVS-111, in a photochemical stroke model.

Local thrombosis of the frontal cortex (Fr1 and Fr3 fields), caused by combination of the intravenous photosensitive dye Rose Bengal administration with focused high-intensity illumination of the frontal bone, was shown to provoke a pronounced deficit in step-through passive avoidance performance in rats without concomitant motor disturbances. N-Phenylacetyl-L-prolylglycine ethyl ester (GVS-111) administered intravenously at a dose of 0.5 mg/kg/day, for the first time 1 h after ischaemic lesion and then for 9 post-operative days, with the last administration 15 min before testing, attenuated the deficit. This treatment significantly diminished the volume of the infarcted area. Thus, post-ischaemic injection of GVS-111 demonstrated both cognition-restoring and neuroprotective properties. The cognition-restoring effect is probably based on an increase in neocortical and hippocampal neuronal plasticity. Neuroprotective effects of GVS-111 combine antioxidant activity with the ability to attenuate glutamate-provoked neurotoxicity and block voltage-gated ionic channels, i.e. the compound mitigates the main metabolic shifts involved in pathogenesis of brain ischaemia.

Animals↗

PubMed1999

Schizophrenia and the disconnection hypothesis.

This article reviews the disconnection hypothesis of schizophrenia and presents a mechanistic account of how dysfunctional integration among neuronal systems might arise. This neurobiological account is based on some simple observations about schizophrenia and the central role that neuronal plasticity plays in shaping the connections, and the ensuing dynamics, that underlie brain function. The particular hypothesis put forward here is that the pathophysiology of schizophrenia is expressed at the level of modulation of associative changes in synaptic efficacy, specifically the modulation of plasticity in those brain systems that are responsible for learning, memory and emotion. This modulation is mediated by ascending neurotransmitter systems that (i) have been implicated in schizophrenia and (ii) are known to be involved in consolidating synaptic connections during learning. The proposed pathophysiology would translate, in functional terms, into a disruption of the reinforcement of adaptive behaviour that is consistent with the disintegrative aspects of schizophrenic neuropsychology.

Brain↗

PubMed2002

Augmentation of allergic early-phase reaction by nerve growth factor.

The allergic early-phase reaction, a hallmark of allergic bronchial asthma, is caused by allergen and immunoglobulin E-dependent mediator release from mast cells. It was previously shown that nerve growth factor (NGF) contributes to acute airway inflammation. This study further investigates the role of NGF in the allergic early-phase reaction using a well-established mouse model of ovalbumin-induced allergic airway inflammation. Treatment of sensitized and aerosol challenged BALB/c mice with blocking anti-NGF antibodies inhibited allergen-induced early-phase reaction and suppressed airway inflammation. Transgenic mice constitutively overexpressing NGF in the airways (Clara-cell secretory protein promoter [CCSP]-NGF-tg) were employed and compared with wild-type animals. In sensitized and challenged CCSP-NGF-tg mice, early-phase reaction, airway inflammation, as well as percental relative increases in serotonin levels were augmented compared with wild-type mice. These effects were paralleled by increased serotonin levels in the airways, whereas immunoglobulin E levels remained unaffected. Furthermore, CCSP-NGF-tg mice developed an increased reactivity of sensory neurons in response to inhaled capsaicin demonstrating NGF-mediated neuronal plasticity. These data provide evidence for the functional role of NGF in the development of allergic early phase responses in the airways and the lung.

Acute-Phase Reaction↗

PubMed2003

Mechanosensory-induced behavioural gregarization in the desert locust Schistocerca gregaria.

Desert locusts show an extreme form of phenotypic plasticity, changing between a cryptic solitarious phase and a swarming gregarious phase that differ in many aspects of behaviour, physiology and appearance. Solitarious locusts show rapid behavioural phase change in response to tactile stimulation directed to the hind femora. Repeatedly touching as little as one quarter of the anterior (outer) surface area of a hind femur produced full behavioural gregarization within 4 h. Solitarious locusts have approximately 30% more mechanosensory trichoid sensilla on the hind femora than do gregarious locusts but have similar or fewer numbers of sensilla elsewhere on the legs. Tactile stimulation of a hind femur in solitarious locusts that had been restrained so that they could not move their legs failed to induce any behavioural gregarization. Patterned electrical stimulation of metathoracic nerve 5, which innervates the hind leg, however, produced full gregarization in restrained locusts. Our data show for the first time that the gregarizing signal combines both exteroceptive and proprioceptive components, which travel in both nerves 5B1 and 5B2, and provides us with a powerful experimental method with which to elicit and study neuronal plasticity in this system. Acetic acid odour, a strong chemosensory stimulus that activates the same local processing pathways as exteroceptive stimuli, failed to elicit behavioural gregarization, suggesting an early segregation in the central nervous system of the mechanosensory signals that leads to gregarization.

Acetic Acid↗

PubMed2003

cDNA profiling of epileptogenesis in the rat brain.

Symptomatic temporal lobe epilepsy typically develops in three phases: brain insult --> latency period (epileptogenesis) --> recurrent seizures (epilepsy). We hypothesized that remodeling of neuronal circuits underlying epilepsy is associated with altered gene expression during epileptogenesis. Epileptogenesis was induced by electrically triggered status epilepticus (SE) in rats. Animals were continuously monitored with video-EEG, and the hippocampus and temporal lobe were collected either during epileptogenesis (1, 4 and 14 days) or after the first spontaneous seizures (14 days) for cDNA array analysis. Altogether, 282 genes had altered expression, from which 87 were in the hippocampus and 208 in the temporal lobe (overlap in 13). Assessment of hippocampal gene expression during epileptogenesis indicated that 37 genes were altered in the 1-day group, 12 in the 4-day group and 14 in the 14-day epileptogenesis group. There were 42 genes with altered expression in the 14-day epilepsy group. In the temporal lobe, the number of genes with altered expression was 29 in the 1-day group, 155 in the 4-day group, 32 in the 14-day epileptogenesis group and 62 in the 14-day epilepsy group. Products of the altered genes are involved in neuronal plasticity, gliosis, organization of the cytoskeleton or extracellular matrix, cell adhesion, signal transduction, regulation of cell cycle, and metabolism. As most of these genes have not previously been implicated in epileptogenesis or epilepsy, these data open new avenues for understanding the molecular basis of epileptogenesis and provide new targets for rational development of anti-epileptogenic treatments for patients with an elevated risk of epileptogenesis after brain injury.

Animals↗

PubMed2003

Cdk5 in the adult non-demented brain.

Cyclin-dependent kinase 5 (Cdk5), a Ser/Thr kinase, regulates the phosphorylation of neuronal proteins and thereby influences neuronal morphology, migration and axon growth. Tightly coordinated interactions between Cdk5 and its activator proteins p35 and p39 are critical for the developmental processes of post-mitotic neurons as well as functioning of the adult CNS. Excessive up-regulation of Cdk5 activity leading to hyperphosphorylation of cytoskeletal proteins has been linked to neurodegenerative disorders, such as Alzheimer's disease (AD). On this basis it was proposed that Cdk5 might be a promising drug target. The physiologic role of Cdk5 in the adult CNS has been addressed recently. It was demonstrated that Cdk5 is involved in striatal and hippocampal neuronal plasticity and long-term behavioral changes associated with these processes. On the basis of the newly identified role of Cdk5 in synaptic plasticity, learning and memory the view that Cdk5 represents a good drug target in AD accompanied by cognitive dysfunctions may have to be revisited. Alternatively, targeting the mechanisms up-stream of Cdk5 leading to deregulation of Cdk5 activity, such as proteolytic cleavage of its activating subunits may prove to be more beneficial as a therapeutical approach.

Animals↗

PubMed2002

Differential rat brain expression of EGR proteins and of the transcriptional corepressor NAB in response to acute or chronic cocaine administration.

Members of the Egr family of early genes are known to play a prominent role in neuronal plasticity. Using in situ hybridization, we report the induction in the rat forebrain of the immediate early gene egr-1 and of the transcriptional repressor NAB2 in response to acute or repeated cocaine administration. A single exposure to cocaine enhanced the expression of egr-1 in dopaminergic brain areas. Chronic cocaine treatment was not followed by induction of egr-1 mRNA initially, but only 12 h following the last injection, whereas Egr-1 binding activity was maintained elevated at 2 h and was increased again at 12 h. Expression of the Egr corepressor NAB2, but not NAB1, was rapidly and transiently stimulated by cocaine. Both acute and chronic cocaine treatment displayed biphasic NAB2 mRNA expression. It appears that NAB2 operates as an inducible regulator of gene expression in postmitotic neurons. Egr-3 displayed an expression profile similar to that of Egr-1 in response to acute cocaine injection and was expressed slightly earlier upon repeated cocaine treatment. Regulation of Egr transcription factors during chronic cocaine treatment appears to differ from that of the AP1 transcription factor, since Egr-1 and Egr-3 were induced after both acute and repeated cocaine administration, and that neither Egr-2 nor Egr-3 substituted for Egr-1 after chronic cocaine treatment. Our data suggest that Egr-1, Egr-3, and NAB2 are the key members of their families that regulate expression of Egr target genes.

Animals↗

PubMed2004

Cortical reorganization--effects of intensive therapy.

Recovery from hemiparesis after stroke largely depends on widespread functional and structural neuronal plasticity. Based on animal studies of rehabilitative and pharmacological interventions on recovery, recent neuroscientific findings suggest that new rehabilitative interventions may also have benefits by modulating neuroplastic mechanisms in stroke patients. Neurofunctional imaging methods such as Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI) as well as transcranial magnetic stimulation (TMS) now permit direct studies of training-induced plasticity in stroke patients. Prospectively conducted studies using these techniques have investigated how plasticity relates to recovery of motor function and how intensive training modulates cortical reorganization. Despite technical and methodological differences, consistent neuroanatomic findings on training-induced reorganization of the motor system have been reported. These discoveries have important implications for the future development of neurorehabilitative training methods. With continuously improving methods to study cortical reorganization and over 100 randomized clinical trials on stroke rehabilitation published during the past five years, this promises to be an exciting time in stroke rehabilitation research.

Cerebral Cortex↗

PubMed1991

Functional recovery and collateral neuronal sprouting examined in young and aged rats following a partial neural lesion.

The rat pineal gland was chosen as a model system to study how aging affects the capacity of surviving neurons to compensate for partial destruction of a neural pathway. The pineal gland receives bilateral overlapping sympathetic innervation from the two internal carotid nerves, whose activity regulates several aspects of pineal metabolism in a circadian fashion. The most dramatic of these is the marked nighttime increase in the activity of N-acetyltransferase, the rate-limiting enzyme in melatonin synthesis. These features allow for the pineal gland to be used as a model system for studies on neuronal plasticity, since it is possible to create specific partial neural lesions and to evaluate functional recovery subsequently at the cellular level. We examined the activity of N-acetyltransferase and the content of melatonin in the pineal gland as indices of pineal function at various time points after unilateral surgical denervation (lesion of one of the two internal carotid nerves) in 4-month-(young) and 25-month-old (aged) rats. At both ages, the nighttime levels of the two parameters were significantly lower 8 h after this lesion than in sham-operated animals of the same age, indicating impaired function. When examined at later time points (i.e., 1.5 and 10 days after this lesion), both young and aged animals exhibited full recovery in these two parameters. Measurement of specific neuronal uptake of [3H]norepinephrine was utilized as an index of the number of sympathetic varicosities innervating the pineal gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed2003

Neurotrophins in allergic airway dysfunction: what the mouse model is teaching us.

Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are potent mediators of neuronal plasticity in the adult. There is increasing evidence that they regulate a variety of immune functions as well. Thus, neurotrophins are candidate molecules for neuroimmune interactions in allergic bronchial asthma, where elevated neurotrophin levels have been reported. In a mouse model of allergic airway inflammation we have identified macrophages and lymphocytes as additional cellular sources of NGF and BDNF in the inflamed lung. There was an unusual time course of BDNF in bronchoalveolar lavage fluid. BDNF levels peaked 1 week after the last allergen challenge, and did not correlate with the time course of the inflammatory response. In a series of experiments using blocking anti-NGF and anti-BDNF antibodies, we have shown that NGF specifically enhances inflammation and the allergic early-phase response. In contrast, BDNF influenced chronic airway obstruction and local neuronal hyperreactivity without affecting inflammation. Using transgenic mice overexpressing NGF in the airway epithelium, we have confirmed the data obtained from anti-NGF experiments. Allergen-challenged NGF overexpressors displayed a markedly augmented airway inflammation, early-phase response, and sensory irritation compared to wild-type mice. Studies with p75-NTR (-/-) knockout mice showed that these NGF effects are at least in part mediated by the low-affinity neurotrophin receptor. Thus, our experiments suggest that NGF and BDNF have a profound, but differential impact on allergic airway dysfunction.

Allergens↗

PubMedDate not supplied

[The relationship between the Wnt signaling and the psychiatric diseases].

It has been demonstrated that the neuronal plasticity and resilience could participate in the pathophysiology of neurodegenerative diseases such as Alzheimer and others like depression and schizophrenia. Recently, it has been proposed a new intracellular pathway, known as Wnt pathway, which could be related to the induction of the plastic changes mentioned above. The glycogen synthase kinase-3beta (GSK-3beta), one of the main enzymes of the Wnt signaling, has been associated to Alzheimer;s and schizophrenia diseases etiology. Furthermore, the mood stabilizing agents;s action mechanism, like lithium and valproic acid, implies the inhibition of this protein. The issue of this work is to describe the proteins that are recruited when this pathway is activated and the GSK-3beta role in the pathologies mentioned.

Alzheimer Disease↗

PubMed2006

The role of the endoplasmic reticulum Ca2+ store in the plasticity of central neurons.

The smooth endoplasmic reticulum (SER) is a well-characterized buffer and source of Ca2+ in both axonal and dendritic compartments of neurons. Ca2+ release from the SER can be evoked by stimulation of the ryanodine receptor or the inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] receptor. Both receptors can couple to the activation of neurotransmitter-gated receptors and voltage-gated Ca2+ channels on the plasma membrane, thus enabling the SER to discriminate between different types of neuronal activity. In axonal terminals, Ca2+-induced Ca2+ release (CICR) mediates spontaneous, evoked and facilitated neurotransmission. Store release might also regulate the mobilization and recycling of synaptic vesicles. In the dendritic compartment, the distribution of Ins(1,4,5)P3 receptors and ryanodine receptors influences the intracellular encoding of neuronal activity. Thus, the functionality of the Ca2+ store can affect both the polarity and the spatial extent of Ca2+-dependent shifts in synaptic efficacy. In hippocampal neurons, for example, CICR in the spine heads underlies homosynaptic plasticity, whereas heterosynaptic plasticity is mediated by Ins(1,4,5)P3-dependent Ca2+ signalling. Purkinje neurons primarily express Ins(1,4,5)P3 receptors in the spine heads, and long-term depression of synaptic efficacy is crucially dependent on Ins(1,4,5)P3.

Animals↗

PubMed2004

Experience-dependent immediate early gene expression in the adult central nervous system: evidence from enriched-environment studies.

Here I discuss evidence from our group's work that implicates the immediate early genes NGFI-A and arc as possible regulators of neuronal plasticity. The enriched environment (EE) paradigm has been demonstrated to induce neural plasticity in both developing and mature mammals. Others and we have recently demonstrated that adult rats placed within an enriched environment underwent central nervous system-wide increases in the expression levels for the IEGs NGFI-A and arc. The relationships between the altered expression profiles for both genes in response to an EE exposure, and their putative role in orchestrating network restructuring in response to enhanced environmental complexity are discussed.

AIDS-Related Complex↗