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Results for “Neuronal Plasticity”

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PubMed2004

Morphine exposure and abstinence define specific stages of gene expression in the rat nucleus accumbens.

Intermittent exposure to addictive drugs causes long-lasting changes in responsiveness to these substances due to persistent molecular and cellular alterations within the meso-corticolimbic system. In this report, we studied the expression profiles of 159 genes in the rat nucleus accumbens during morphine exposure (14 days, 10 mg/kg s.c.) and drug-abstinence (3 weeks). We used real-time quantitative PCR to monitor gene expression after establishing its sensitivity and resolution to resolve small changes in expression for genes in various abundance classes. Morphine-exposure (5 time points) and subsequent abstinence (6 time points) induced phase-specific temporal gene expression of distinct functional groups of genes, for example, short-term homeostatic responses. Opiate withdrawal appeared to be a new stimulus in terms of gene expression and mediates a marked wave of gene repression. Prolonged abstinence resulted in persistently changed expression levels of genes involved in neuronal outgrowth and re-wiring. Our findings substantiate the hypothesis that this new gene program, initiated upon morphine-withdrawal, may subserve long-term neuronal plasticity involved in the persistent behavioral consequences of repeated drug-exposure.

Adaptation, Physiological↗

PubMed2002

[Physiopathology of the enteric nervous system: recent advances and clinical implications].

Enteric neuropathies may significantly affect the patient's quality of life, although they have a fatal outcome only in a minority of cases. Motor derangement (often, hypomotility) is a typical feature of primary and secondary neuropathies affecting the myenteric plexus. This review addresses some pathophysiological aspects of enteric neuropathies and tries to outline the limitations of the experimental evidence obtained so far as well as some questions that can possibly receive an answer by applying new concepts and new techniques. In particular, the concept of neuronal plasticity, originally developed by investigators studying the central nervous system, is discussed and applied to the enteric microenvironment, with specific reference to adaptive phenomena occurring during intestinal inflammation. The role of neurotrophins and the potential therapeutic applications are also briefly discussed.

Animals↗

PubMed2006

Axonal plasticity is associated with motor recovery following amphetamine treatment combined with rehabilitation after brain injury in the adult rat.

Clinical and laboratory studies have suggested that amphetamine treatment when paired with rehabilitation results in improved recovery of function after stroke or traumatic brain injury. In the present study, we investigated whether new anatomical pathways developed in association with improved motor function after brain damage and amphetamine treatment linked with rehabilitation. Following a unilateral sensorimotor cortex lesion in the adult rat, amphetamine (2 mg/kg) was administered in conjunction with physiotherapy sessions on postoperative days two and five. Physiotherapy was continued twice daily for the first 3 weeks after injury, and then once daily until week six. Performance on skilled forelimb reaching and ladder rung walking was used to assess motor improvement. Our results show that animals with sensorimotor cortical lesions receiving amphetamine treatment linked with rehabilitation had significant improvement in both tasks. Neuroanatomical tracing of efferent pathways from the opposite, non-damaged cortex resulted in the novel finding that amphetamine treatment linked with rehabilitation, significantly increased axonal growth in the deafferented basilar pontine nuclei. These results support the notion that pharmacological interventions paired with rehabilitation can enhance neuronal plasticity and thereby improve functional recovery after CNS injury.

Amphetamine↗

PubMed2005

Recovery and brain reorganization after stroke in adult and aged rats.

Stroke is a prevalent and devastating disorder, and no treatment is currently available to restore lost neuronal function after stroke. One unique therapy that improves recovery after stroke is neutralization of the neurite inhibitory protein Nogo-A. Here, we show, in a clinically relevant model, improved functional recovery and brain reorganization in the aged and adult rat when delayed anti-Nogo-A therapy is given after ischemic injury. These results support the efficacy of Nogo-A neutralization as treatment for ischemic stroke, even in the aged animal and after a 1-week delay, and implicate neuronal plasticity from unlesioned areas of the central nervous system as a mechanism for recovery.

Age Factors↗

PubMed1990

Protein structure: the primary substrate for memory.

The motility of protein structure, the existence of discrete conformational states, and the multifarious modes of supramolecular protein organization seem to underlie neuronal plasticity. These aspects of protein structure are surveyed from the viewpoint of their potential role in short-term and long-term memory. It is suggested that long-term memory may ensue from the remodelling of synaptic protein assemblies requiring extra copies of pre-existing proteins.

Animals↗

PubMed1997

Synaptic beta-amyloid precursor proteins increase with learning capacity in rats.

The precursor proteins of Alzheimer's disease beta-amyloid peptide, the beta-amyloid precursor protein isoforms, comprise a family of neuronal proteins with synaptic localization whose physiological roles in brain are poorly understood. One possible role for synaptic proteins is involvement in neuronal plasticity. After exposure to an enriched environment compared to impoverished conditions, rats exhibited superior cognitive capacity. Up to approximately four-fold increased overall levels of beta-amyloid precursor proteins were found in cortical/subcortical tissue of the enriched animals displaying significantly more synapses immunoreactive for the different beta-amyloid precursor protein isoforms (beta-amyloid precursor protein695- and beta-amyloid precursor protein751/770) in hippocampus and adjacent occipital cortex. This correlation thus provides in vivo evidence for an association of beta-amyloid precursor proteins with plastic changes induced by complex environment with consequences for cognitive functions and suggests that impaired beta-amyloid precursor protein metabolism at synapses might contribute to brain dysfunction in Alzheimer's disease.

Amyloid beta-Protein Precursor↗

PubMed2006

Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength.

The CB1 cannabinoid receptor has attracted much recent interest because of the observation that CB1 receptor antagonists have efficacy in treating metabolic syndrome and obesity. CB1 receptors also mediate most of the psychotropic effects of Delta9-tetrahydrocannabinol (Delta9THC), the principal psychoactive component of cannabis. In addition, they are one component of an interesting and widespread paracrine signaling system, the endocannabinoid system. The endocannabinoid system is comprised of cannabinoid receptors, endogenous cannabinoids, and the metabolic pathways responsible for their synthesis and degradation. The details of the endocannabinoid system have been most thoroughly studied in the brain. Here it has been shown to be intimately involved in several forms of neuronal plasticity. That is, activation of CB1 receptors by endocannabinoids produces either short- or long-term changes in the efficacy of synaptic transmission. The behavioral consequences of these changes are many, but some of the most striking and relevant to the current symposium are those associated with endogenous reward and consumptive behavior.

Appetite Regulation↗

PubMed2003

Plasticity in the visual system is correlated with a change in lifestyle of solitarious and gregarious locusts.

We demonstrate pronounced differences in the visual system of a polyphenic locust species that can change reversibly between two forms (phases), which vary in morphology and behavior. At low population densities, individuals of Schistocerca gregaria develop into the solitarious phase, are cryptic, and tend to avoid other locusts. At high densities, individuals develop instead into the swarm-forming gregarious phase. We analyzed in both phases the responses of an identified visual interneuron, the descending contralateral movement detector (DCMD), which responds to approaching objects. We demonstrate that habituation of DCMD is fivefold stronger in solitarious locusts. In both phases, the mean time of peak firing relative to the time to collision nevertheless occurs with a similar characteristic delay after an approaching object reaches a particular angular extent on the retina. Variation in the time of peak firing is greater in solitarious locusts, which have lower firing rates. Threshold angle and delay are therefore conserved despite changes in habituation or behavioral phase state. The different rates of habituation should contribute to different predator escape strategies or flight control for locusts living either in a swarm or as isolated individuals. For example, increased variability in the habituated responses of solitarious locusts should render their escape behaviors less predictable. Relative resistance to habituation in gregarious locusts should permit the continued responsiveness required to avoid colliding with other locusts in a swarm. These results will permit us to analyze neuronal plasticity in a model system with a well-defined and controllable behavioral context.

Action Potentials↗

PubMed1999

Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions.

Compelling evidence has accumulated over the last several years from our laboratory, as well as others, indicating that central hyperactive states resulting from neuronal plastic changes within the spinal cord play a critical role in hyperalgesia associated with nerve injury and inflammation. In our laboratory, chronic constriction injury of the common sciatic nerve, a rat model of neuropathic pain, has been shown to result in activation of central nervous system excitatory amino acid receptors and subsequent intracellular cascades including protein kinase C translocation and activation, nitric oxide production, and nitric oxide-activated poly(ADP ribose) synthetase activation. Similar cellular mechanisms also have been implicated in the development of tolerance to the analgesic effects of morphine. A recently observed phenomenon, the development of "dark neurons," is associated with both chronic constriction injury and morphine tolerance. A site of action involved in both hyperalgesia and morphine tolerance is in the superficial laminae of the spinal cord dorsal horn. These observations suggest that hyperalgesia and morphine tolerance may be interrelated at the level of the superficial laminae of the dorsal horn by common neural substrates that interact at the level of excitatory amino acid receptor activation and subsequent intracellular events. The demonstration of interrelationships between neural mechanisms underlying hyperalgesia and morphine tolerance may lead to a better understanding of the neurobiology of these two phenomena in particular and pain in general. This knowledge may also provide a scientific basis for improved pain management with opiate analgesics.

Animals↗

PubMed2002

Acute administration of antipsychotics modulates Homer striatal gene expression differentially.

Typical and atypical antipsychotics, the mainstay of schizophrenia pharmacotherapy, have been demonstrated to affect differently neuronal gene expression in several preclinical paradigms. Here we report the differential gene expression of the glutamatergic post-synaptic density proteins Homer and PSD-95 in rat forebrain following acute haloperidol or olanzapine treatment. Moreover, considering the extensive interactions between dopaminergic and opioidergic systems we also measured striatal preproenkephalin mRNA. Male Sprague-Dawley rats were treated with haloperidol 1 mg/kg or olanzapine 0.5 mg/kg or vehicle, i.p. and sacrificed 3 h after the injection. Homer gene expression was significantly increased in caudate putamen and nucleus accumbens of rats treated with haloperidol and in the core of accumbens of rats treated with olanzapine. No changes were detected for Homer in prefrontal and parietal cortex in any of the experimental groups. PSD-95 gene expression was not modulated in our paradigm by administration of either typical or atypical antipsychotics. These results (1) suggest a differential modulation of Homer by typical and atypical antipsychotics; (2) confirm that Homer can be induced as an early gene with putative direct effect on neuronal plasticity and (3) demonstrate different response to antipsychotics by different classes of postsynaptic density proteins at glutamatergic synapses.

Animals↗

PubMed2006

Acetylcholine release at neuromuscular junctions of adult tottering mice is controlled by N-(cav2.2) and R-type (cav2.3) but not L-type (cav1.2) Ca2+ channels.

The mutation in the alpha(1A) subunit gene of the P/Q-type (Ca(v)2.1) Ca(2+) channel present in tottering (tg) mice causes ataxia and motor seizures that resemble absence epilepsy in humans. P/Q-type Ca(2+)channels are primarily involved in acetylcholine (ACh) release at mammalian neuromuscular junctions. Unmasking of L-type (Ca(v)1.1-1.2) Ca(2+) channels occurs in cerebellar Purkinje cells of tg mice. However, whether L-type Ca(2+) channels are also up-regulated at neuromuscular junctions of tg mice is unknown. We characterized thoroughly the pharmacological sensitivity of the Ca(2+) channels, which control ACh release at adult tg neuromuscular junctions. Block of N- and R-type (Ca(v)2.2-2.3), but not L-type Ca(2+) channels, significantly reduced quantal content of end-plate potentials in tg preparations. Neither resting nor KCl-evoked miniature end-plate potential frequency differed significantly between tg and wild type (WT). Immunolabeling of Ca(2+) channel subunits alpha(1A), alpha(1B), alpha(1C), and alpha(1E) revealed an apparent increase of alpha(1B), and alpha(1E) staining, at tg but not WT neuromuscular junctions. This presumably compensates for the deficit of P/Q-type Ca(2+)channels, which localized presynaptically at WT neuromuscular junctions. No alpha(1C) subunits juxtaposed with pre- or postsynaptic markers at either WT or tg neuromuscular junctions. Thus, in adult tg mice, immunocytochemical and electrophysiological data indicate that N- and R-type channels both assume control of ACh release at motor nerve terminals. Recruitment of alternate subtypes of Ca(2+) channels to control transmitter release seems to represent a commonly occurring method of neuronal plasticity. However, it is unclear which conditions underlie recruitment of Ca(v)2 as opposed to Ca(v)1-type Ca(2+) channels.

Acetylcholine↗

PubMed2003

Selective disruption of stimulus-reward learning in glutamate receptor gria1 knock-out mice.

Glutamatergic neurotransmission via AMPA receptors has been an important focus of studies investigating neuronal plasticity. AMPA receptor glutamate receptor 1 (GluR1) subunits play a critical role in long-term potentiation (LTP). Because LTP is thought to be the cellular substrate for learning, we investigated whether mice lacking the GluR1 subunit [gria1 knock-outs (KO)] were capable of learning a simple cue-reward association, and whether such cues were able to influence motivated behavior. Both gria1 KO and wild-type mice learned to associate a light/tone stimulus with food delivery, as evidenced by their approaching the reward after presentation of the cue. During subsequent testing phases, gria1 KO mice also displayed normal approach to the cue in the absence of the reward (Pavlovian approach) and normal enhanced responding for the reward during cue presentations (Pavlovian to instrumental transfer). However, the cue did not act as a reward for learning a new behavior in the KO mice (conditioned reinforcement). This pattern of behavior is similar to that seen with lesions of the basolateral nucleus of the amygdala (BLA), and correspondingly, gria1 KO mice displayed impaired acquisition of responding under a second-order schedule. Thus, mice lacking the GluR1 receptor displayed a specific deficit in conditioned reward, suggesting that GluR1-containing AMPA receptors are important in the synaptic plasticity in the BLA that underlies conditioned reinforcement. Immunostaining for GluR2/3 subunits revealed changes in GluR2/3 expression in the gria1 KOs in the BLA but not the central nucleus of the amygdala (CA), consistent with the behavioral correlates of BLA but not CA function.

Acoustic Stimulation↗

PubMed2000

Delayed and blunted induction of mRNA for tissue plasminogen activator in the brain of old rats following pentylenetetrazole-induced seizure activity.

The ability of the rodent brain to support plasticity-related phenomena declines with increasing age. Here we investigated the extent to which old rats retain the capacity to initiate transcription for immediate early genes, particularly as it relates to brain plasticity, in response to a strong stimulus. The intraperitoneal administration of pentylenetetrazole (PTZ) to rats of various ages evoked tonic-clonic seizures. Using an RNA gel-blot and in situ hybridization analysis, we found that 1 hour after the onset of seizure, messenger RNA (mRNA) for tissue plasminogen activator (TPA) was increased approximately 3.7-fold in the hippocampi of 3-month-old rats. The levels of TPA mRNA in the hippocampi and cortices of 3-month-old rats returned to control levels by 3 hours after PTZ administration. The levels of TPA mRNA increased 2.5-fold in the hippocampi of 18-month-old rats and 1.8-fold in the brains of the 28-month-old-rats at 3 hours and returned to basal levels by 15 hours following PTZ treatment. Quantitatively similar increases were calculated for the cortex. At peak induction the transcripts were localized throughout the cortical layers of the 3-month-old rats, whereas the TPA mRNA expression was restricted to cortical layer V of the older rats. Our results suggest that although the aging brain retains the capacity to respond to chemically induced seizures, the induction of TPA mRNA is temporarily delayed and the levels are diminished with increasing age. Because TPA has been implicated in neuronal plasticity, this finding suggests that immediate early genes are important factors in the limited plasticity of the aging brain.

Aging↗

PubMed2004

Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor.

A diet high in total fat (HF) reduces hippocampal levels of brain-derived neurotrophic factor (BDNF), a crucial modulator of synaptic plasticity, and a predictor of learning efficacy. We have evaluated the capacity of voluntary exercise to interact with the effects of diet at the molecular level. Animal groups were exposed to the HF diet for 2 months with and without access to voluntary wheel running. Exercise reversed the decrease in BDNF and its downstream effectors on plasticity such as synapsin I, a molecule with a key role in the modulation of neurotransmitter release by BDNF, and the transcription factor cyclic AMP response element binding protein (CREB), important for learning and memory. Furthermore, we found that exercise influenced the activational state of synapsin as well as of CREB, by increasing the phosphorylation of these molecules. In addition, exercise prevented the deficit in spatial learning induced by the diet, tested in the Morris water maze. Furthermore, levels of reactive oxygen species increased by the effects of the diet were decreased by exercise. Results indicate that exercise interacts with the same molecular systems disrupted by the HF diet, reversing their effects on neural function. Reactive oxygen species, and BDNF in conjunction with its downstream effectors on synaptic and neuronal plasticity, are common molecular targets for the action of the diet and exercise. Results unveil a possible molecular mechanism by which lifestyle factors can interact at a molecular level, and provide information for potential therapeutic applications to decrease the risk imposed by certain lifestyles.

Animals↗

PubMed2004

Regulation of Nogo and Nogo receptor during the development of the entorhino-hippocampal pathway and after adult hippocampal lesions.

Axonal regeneration in the adult CNS is limited by the presence of several inhibitory proteins associated with myelin. Nogo-A, a myelin-associated inhibitor, is responsible for axonal outgrowth inhibition in vivo and in vitro. Here we study the onset and maturation of Nogo-A and Nogo receptor in the entorhino-hippocampal formation of developing and adult mice. We also provide evidence that Nogo-A does not inhibit embryonic hippocampal neurons, in contrast to other cell types such as cerebellar granule cells. Our results also show that Nogo and Nogo receptor mRNA are expressed in the adult by both principal and local-circuit hippocampal neurons, and that after lesion, Nogo-A is also transiently expressed by a subset of reactive astrocytes. Furthermore, we analyzed their regulation after kainic acid (KA) treatment and in response to the transection of the entorhino-hippocampal connection. We found that Nogo-A and Nogo receptor are differentially regulated after kainic acid or perforant pathway lesions. Lastly, we show that the regenerative potential of lesioned entorhino-hippocampal organotypic slice co-cultures is increased after blockage of Nogo-A with two IN-1 blocking antibodies. In conclusion, our results show that Nogo and its receptor might play key roles during development of hippocampal connections and that they are implicated in neuronal plasticity in the adult.

Animals↗

PubMedDate not supplied

Temporal dynamics of degenerative and regenerative events associated with cerebral ischemia in aged rats.

BACKGROUND AND PURPOSE: The age-related decline in plasticity of the brain may be one factor underlying the poor functional recovery after stroke. In the present work we tested the hypothesis that the attenuation of neural plasticity could be the result of an age-related REDUCTION in the upregulation of factors promoting brain plasticity (microtubule-associated protein 1B [MAP1B], beta-amyloid precursor protein [betaAPP]), and an age-related INCREASE in glial reactivity and the accumulation of Abeta, a proteolytic cleavage product of betaAPP with neurotoxic properties. METHODS: Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. The functional outcome was assessed in neurobehavioral tests 3, 7, 14 and 28 days after surgery. At the indicated time points, brains were removed and immunostained for glial cells. Abeta, as well as the markers of brain plasticity, betaAPP and MAP1B. RESULTS: Histologically, in young rats there was a gradual activation of both microglia and astrocytes that peaked by days 14-28 with the formation of a glial scar. In contrast, aged rats showed an accelerated astrocytic and microglial reaction that peaked in the first week after stroke. The expression patterns of a growth-associated phenotype of betaAPP as well as with MAP1B accumulation in varicosities along axons in cortical areas affected by stroke peaked between days 14 and 28 in young animals. In aged rats their expression was both delayed (28 days) and reduced. In addition the carboxy terminal fragment of betaAPP steadily accumulated over time and reached a maximum by day 14 in aged rats as compared to 28 days in young rats. CONCLUSIONS: These results suggest that a temporally anomalous gliotic reaction to cerebral ischemia in aged rats in conjunction with a late and limited upregulation of neuronal plasticity proteins as well as a diminished neurogenesis potential lead to the prevalence of scar tissue that impedes functional recovery from stroke.

Aging↗

PubMed2005

[Paralyzed face. Ansa-cervicalis-nervi-hypoglossi].

INTRODUCTION: For 100 years hypoglossal-facial nerve anastomosis (HFA) has been a common surgical procedure for reanimation of paralyzed mimic muscles of the face after axotomy of the facial nerve. However, the denervation and subsequent scarred degeneration of the target muscles of the hypoglossal nerve often results in unfavorable late effects for speech and swallowing. Therefore, the ansa cervicalis nervi hypoglossi-facial nerve anastomosis (ACHFA) can be an alternative to avoid such late effects. As a branch of the hypoglossal nerve the ansa cervicalis innervates the infrahyoidal muscles. Neck dissection surgery proved that resection of the ansa cervicalis causes no side effects for swallowing because of several nerve anastomoses to the cervical plexus. PATIENTS AND METHOD: We compared our clinical results of eight cases following a delayed ACHFA with our own experiences after HFA and results from the literature. RESULTS: We found a reanimation rate lower than usually seen after HFA only in the target muscles of the forehead. This may be caused by a reduced neuronal plasticity of the ansa cervicalis. However, in the target muscles of the other two facial nerve branches we observed the same good results one would expect after HFA. There were no late side effects for swallowing and speech though.

Adult↗

PubMed2006

Age and neuroinflammation: a lifetime of psychoneuroimmune consequences.

This article reviews the literature indicating that the innate immune cells of the brain become more reactive with age. Although it is unclear how glia reactivity increases, emerging evidence suggests these alterations allow exacerbated neuroinflammation and sickness behavior following peripheral immune activation. This amplified or prolonged exposure to inflammatory cytokines in the brain may impair neuronal plasticity and underlie a heightened neuroinflammatory response in the aged that also may lead to other neurobehavioral impairments such as delirium, depression, and, potentially, the onset of neurologic disease. Therefore pharmacologic strategies to decrease neuroinflammation associated with infection may be important for improving recovery from sickness and reducing neurobehavioral deficits in the elderly.

Aging↗