ABSTRACT
ABSTRACT Background: Enriched environment (EE) is a simple and effective intervention to improve cognitive function in post-stroke cognitive impairment (PSCI), partly due to the rebalancing of the cholinergic signaling pathway in the hippocampus. α7-nicotinic acetylcholine receptor (α7-nAChR) is a cholinergic receptor whose activation inhibits inflammation and promotes the recovery of neurological function in PSCI patients. However, it is still unclear whether EE can regulate α7-nAChR and activate the cholinergic anti-inflammatory pathway (CAP) in PSCI. Objective: To investigate the effects of EE on cognitive impairment, and the role of α7-nAChR in PSCI. Methods: A PSCI rat model was induced by middle cerebral artery occlusion and reperfusion (MCAO/R) and were reared in standard environment (SE) or EE for 28d, control group with sham surgery. Cognitive function was determined by Morris water maze test. The long-term potentiation (LTP) was assessed by Electrophysiology. Histopathological methods were used to determine infarct volume, α7-nAChR expression and the cytokines and cholinergic proteins expression. Results: Compared with SE group, rats in EE group had better cognitive function, higher expression of α7-nAChR positive neurons in hippocampal CA1 region. In addition, EE attenuated unfavorable changes induced by MCAO/R in cytokines and cholinergic proteins, and also enhanced LTP promoted by nicotine and attenuated by α-BGT; but showed no significantly difference in infarct volume. Conclusions: EE markedly improves cognitive impairment and enhances neuroplasticity in PSCI rats, which may be closely related to enhancement of α7-nAChR expression.
RESUMO Introdução: O ambiente enriquecido (AE) é uma intervenção simples e eficaz para melhorar a função cognitiva no comprometimento cognitivo pós-AVC, em parte devido ao reequilíbrio da via de sinalização colinérgica no hipocampo. O receptor nicotínico α7 de acetilcolina (α7-nAChR) é um receptor colinérgico cuja ativação inibe inflamação e promove a recuperação da função neurológica em pacientes com comprometimento cognitivo pós-AVC. No entanto, ainda não está claro se o AE pode regular α7-nAChR e ativar a via anti-inflamatória colinérgica (VAC) em comprometimento cognitivo pós-AVC. Objetivo: Investigar os efeitos do AE no comprometimento cognitivo e o papel do α7-nAChR no comprometimento cognitivo pós-AVC. Métodos: Modelo de comprometimento cognitivo pós-AVC foi induzido em ratos por oclusão e reperfusão da artéria cerebral média (MCAO/R), que foram criados em ambiente padrão (AP) ou em AE por 28d; grupo controle com cirurgia simulada. A função cognitiva foi determinada pelo teste do labirinto aquático de Morris. A potenciação de longo prazo (PLP) foi avaliada por eletrofisiologia. Métodos histopatológicos foram usados para determinar o volume do infarto, a expressão de α7-nAChR e a expressão de citocinas e proteínas colinérgicas. Resultados: Em comparação com o grupo AP, os ratos do grupo AE tiveram melhor função cognitiva, com maior expressão de neurônios positivos para α7-nAChR na região CA1 do hipocampo. Além disso, o AE atenuou alterações desfavoráveis induzidas por MCAO/R em citocinas e proteínas colinérgicas, e também aumentou a PLP promovida pela nicotina e atenuada por α-BGT, mas não mostrou nenhuma diferença significativa no volume do infarto. Conclusão: O AE melhora acentuadamente o comprometimento cognitivo e aumenta a neuroplasticidade em ratos com comprometimento cognitivo pós-AVC, o que pode estar intimamente relacionado ao aumento da expressão de α7-nAChR.
Subject(s)
Humans , Animals , Rats , Stroke , Cognitive Dysfunction , Long-Term Potentiation/physiology , Environment , alpha7 Nicotinic Acetylcholine Receptor/physiology , alpha7 Nicotinic Acetylcholine Receptor/chemistryABSTRACT
SUMMARY OBJECTIVE The study aims to explore the relationship between preoperative anxiety and chronic postoperative pain. METHODS A total of forty rats were divided into four groups, control, single-prolonged stress alone, Hysterectomy alone, and SPS+ Hysterectomy. The paw withdrawal mechanical thresholds (PWMT) were examined. qRT-PCR and western blotting assay were performed to detect the GFAP expression in astrocytes isolated from the anterior cingulate cortex (ACC) region. In addition, the long-term potentiation (LTP) in ACC was examined. RESULTS Rats in the SPS group or the Hysterectomy alone group had no significant effect on chronic pain formation, but SPS can significantly induce chronic pain after surgery. Astrocytes were still active, and the LTP was significantly increased three days after modeling in the SPS+Hysterectomy group. CONCLUSIONS anxiety can induce chronic pain by activating astrocytes in the ACC region.
RESUMO OBJETIVO O objetivo deste estudo é explorar a relação entre a ansiedade no pré-operatório e a dor crônica no pós-operatório. MÉTODOS Um total de 40 ratos foram divididos em quatro grupos: controle, estresse prolongado (SPS), histerectomia e SPS + histerectomia. Os limiares de retirada da pata em resposta a estímulo mecânico (PWMT) foram examinados. Ensaios qRT-PCR e imunoenzimáticos (western blotting) foram realizados para detectar a expressão de GFAP em astrócitos isolados da região do córtex cingulado anterior (CCA). Além disso, a potenciação de longa duração (LTP) no CCA também foi examinada. RESULTADOS Os ratos no grupo de estresse prolongado e no grupo de histerectomia não apresentaram nenhum efeito significativo na formação de dor crônica. Porém, o estresse prolongado foi capaz de induzir dor crônica significativamente após a cirurgia. Três dias após o modelo, o grupo de SPS + histerectomia ainda apresentava astrócitos ativos e LTP significativamente maior. CONCLUSÃO A ansiedade pode provocar dor crônica através da ativação de astrócitos na região do CCA.
Subject(s)
Animals , Female , Anxiety/complications , Pain, Postoperative/etiology , Astrocytes/metabolism , Chronic Pain/etiology , Pain, Postoperative/psychology , Stress, Psychological/etiology , Time Factors , Random Allocation , Rats, Sprague-Dawley , Pain Threshold/physiology , Long-Term Potentiation/physiology , Disease Models, Animal , Preoperative Period , Chronic Pain/psychology , Glial Fibrillary Acidic Protein/metabolism , Gyrus Cinguli/metabolism , Hindlimb , HysterectomyABSTRACT
We review recent work on three major lines of memory research: a) the possible role of the protein kinase M-zeta (PKMzeta) in memory persistence; b) the processes of “synaptic tagging and capture” in memory formation; c) the modulation of extinction learning, widely used in the psychotherapy of fear memories under the name of “exposure therapy”. PKMzeta is a form of protein kinase C (PKC) that apparently remains stimulated for months after the consolidation of a given memory. Synaptic tagging is a mechanism whereby the weak activation of one synapse can tag it with a protein so other synapses in the same cell can reactivate it by producing other proteins that bind to the tag. Extinction, once mistakenly labeled as a form of forgetting, is by itself a form of learning; through it animals can learn to inhibit a response. We now know it can be modulated by neurotransmitters or by synaptic tagging, which should enable better control of its clinical use.
Subject(s)
Humans , Memory/physiology , Protein Kinase C/physiology , Synapses/physiology , Enzyme Activation/physiology , Extinction, Psychological/physiology , Hippocampus/physiology , Long-Term Potentiation/physiologyABSTRACT
Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.
Subject(s)
Animals , Humans , Central Nervous System Diseases/therapy , Electric Stimulation/methods , Long-Term Potentiation/physiology , Long-Term Synaptic Depression/physiology , Photic Stimulation/methods , Central Nervous System Diseases/physiopathologyABSTRACT
OBJETIVES: Diabetes mellitus is a major public health concern in many regions of the world, including the Caribbean. Diabetes is associated with multi-system pathology and central nervous system complications have been receiving increasing attention (dementia, cognitive decline and memory loss). While such pathology has been shown to be associated with long term derangement in glucose metabolism,less is known about the effects of acute changes in glucose concentration on neuronal function. This study assesses the effects of acute changes in glucose concentration upon neuronal transmission and neuronal plasticity. METHODS: We made use of extracellular recordings from hippocampal slices of young adult rats and exposed them to changes in glucose concentration for 60 minutes before assessing synaptic plasticity. Experiments were carried out at both 30ºC and 35ºC. RESULTS: At 30ºC, glucose concentrations of 30 mM and 4 mM had little effect upon population spike potentials (PSP). However, reducing glucose concentration to 2 mM, 1 mM and 0 mM respectively resulted in a progressive decrease in the size of PSP until they were completely abolished. Similar results were observed at 35ºC except that 30 mM caused a significant increase in PSP size. Changes in glucose concentration had no effect upon synaptic plasticity at either 30ºC or 35ºC except below 2 mM glucose. CONCLUSION: Acute changes in glucose concentration have a limited impact on neuronal transmission unless concentrations drop below 2 mM. However, there seems to be little impairment of synaptic plasticity even at very low concentrations of glucose. We suggest that short term acute changes in glucose concentrations may not contribute directly to the cognitive decline associated with diabetes unless extremely severe.
OBJETIVOS: La diabetes mellitus es una de las principales preocupaciones de la salud pública en muchas regiones del mundo, incluyendo el Caribe. La diabetes se encuentra asociada con una patología multi-sistémica, y en tiempos recientes las complicaciones del sistema nervioso central han estado recibiendo cada vez mayor atención, incluyendo la demencia, el deterioro cognitivo y la pérdida de la memoria. Si bien se ha demostrado que esta patología se encuentra asociada con trastornos a largo plazo del metabolismo de la glucosa, poco se sabe de los efectos de los cambios agudos en la concentración de la glucosa en el funcionamiento neuronal. Este estudio evalúa los efectos de los cambios agudos en la concentración de glucosa, sobre la transmisión y la plasticidad neuronales. MÉTODOS:Se hizo uso de grabaciones extracelulares de segmentos del hipocampo de ratas adultas jóvenes. Las grabaciones fueron expuestas a cambios en la concentración de glucosa durante 60 minutos antes de evaluar la plasticidad sináptica. Los experimentos se llevaron a cabo a 30ºC y 35ºC. RESULTADOS: A 30ºC las concentraciones de glucosa de 30 mM y 4 mM tuvieron poco efecto sobre los potenciales de punta PSP (Population Spike Potentials). Sin embargo, la reducción de la concentración de glucosa a 2 mM, 1 mM y 0 mM respectivamente trajo como resultado una progresiva disminución del tamaño de los PSP hasta llegar a su total anulación. Resultados similares que observaron a 35ºC excepto en el caso de 30 mM, en el que se produjo un aumento significativo en la magnitud de los PSP. Los cambios en la concentración de glucosa no tuvieron efecto alguno sobre la plasticidad sináptica a 30ºC ni a 35ºC excepto por debajo de 2 mM de glucosa. CONCLUSIÓN: Los cambios agudos en la concentración de la glucosa tienen un impacto limitado sobre la transmisión neuronal a menos que las concentraciones caigan por debajo de 2 mM. Sin embargo, al parecer hay poca afectación de la plasticidad sináptica, incluso a concentraciones muy bajas de glucosa. Sugerimos que los cambios agudos a corto plazo de las concentraciones de glucosa pueden no contribuir directamente al deterioro cognitivo asociado con la diabetes, a menos que sea extremadamente severa.
Subject(s)
Animals , Rats , Action Potentials/physiology , Glucose/physiology , Hippocampus/physiology , In Vitro Techniques , Long-Term Potentiation/physiologyABSTRACT
Long-term potentiation (LTP) is the enhancement of postsynaptic responses for hours, days or weeks following the brief repetitive afferent stimulation of presynaptic afferents. It has been proposed many times over the last 30 years to be the basis of long-term memory. Several recent findings finally supported this hypothesis: a) memory formation of one-trial avoidance learning depends on a series of molecular steps in the CA1 region of the hippocampus almost identical to those of LTP in the same region; b)hippocampal LTP in this region accompanies memory formation of that task and of another similar task. However, CA1 LTP and the accompanying memory processes can be dissociated, and in addition plastic events in several other brain regions(amygdala, entorhinal cortex, parietal cortex) are also necessary for memory formation of the one-trial task, and perhaps of many others.
A potenciação de longa duração (LTP) é o aumento de respostas pós-sinápticas durante horas, dias ou semanas após a breve estimulação repetitiva de aferentes pre-sinápticos. Foi proposto durante 30 anos ser a base da memória de longa duração. Vários achados recentes finalmente apoiaram esta hipótese: a) a formação da memória de esquiva inibitória adquirida numa sessão depende de uma cadeia de processos moleculares na região CA1 do hipocampo quase idêntica à da LTP nessa mesma região; b) LTP hipocampal nessa região acompanha a formação da memóría dessa tarefa e de outra semelhante. No entanto, a LTP de CA1 e os processos de memória podem ser dissociados e, fora disso, processos plásticos em outras regiões cerebrais (amígdala, córtex entorrinal, córtex parietal) também são necessários para a formação da memória da tarefa de uma sessão e talvez de muitas outras.
Subject(s)
Animals , Humans , Rats , Hippocampus/physiology , Long-Term Potentiation/physiology , Memory/physiology , Avoidance Learning/physiologyABSTRACT
Research in the field of neurosciences and genetics has given us great insight into the understanding of learning and behavior and changes in the brain in response to experience. It is seen that brain is dynamically changing throughout life and is capable of learning at any time. Critical periods of neuroplasticity for various streams of development are also better understood. Technological advances in non invasive imaging techniques and advances in molecular genetics have helped us understand the basis of many developmental disorders which may help in planning effective intervention strategies.
Subject(s)
Adult , Age Factors , Brain Mapping , Child , Coffin-Lowry Syndrome/diagnosis , Critical Period, Psychological , Developmental Disabilities/diagnosis , Electroencephalography , Female , Fragile X Syndrome/diagnosis , Humans , Infant, Newborn , Long-Term Potentiation/physiology , Magnetic Resonance Imaging , Male , Molecular Biology , Neuronal Plasticity/physiology , Neurons/physiology , Neurophysiology , Neurosciences , Pregnancy , Research , Synapses/physiology , Time FactorsABSTRACT
A number of studies attempting to identify specific risk factors for dementia have noted an inverse relationship between educational background and the likelihood of developing dementia. This idea has been somewhat controversial as educational background can introduce a number of confounding factors that generally affect health and lifestyle. Despite these reservations, there is mounting evidence to support the concept of education (or increased mental activity) producing a functional reserve in the brain, a process that provides some protection against the clinical manifestation of dementia. Long-term potentiation (LTP) is a recognized neural correlate of learning and memory. We have shown recently that LTP reduces the sensitivity of hippocampal neurons to agonists of the neurotransmitter glutamate; additionally, we have reported that LTP protects the neurons from the effects of acute hypoxia. Given that the effect of hypoxia on neurons involves over-stimulation by glutamate, and hypoxia has been implicated in the aetio-pathology of some types of dementia, our observations suggest that LTP has a protective effect on neuronal tissue. Such an interaction offers a physiological basis for the epidemiological evidence that lifelong learning can protect a person from some types of dementia.
Subject(s)
Animals , Humans , Dementia , Educational Status , Learning , Risk Factors , Dementia , Learning , Memory , Glutamic Acid/physiology , Alzheimer Disease/prevention & control , Alzheimer Disease/psychology , Long-Term Potentiation/physiologyABSTRACT
BACKGROUND & OBJECTIVES: The endogenous opioid system plays an important role in cognitive functions and may also contribute to the progression of some kind of dementia. Naloxone has been shown to exert beneficial effects on memory deficits in patients with senile dementia and reverse some of the effects induced by endogeneous opioids. We therefore investigated the effects of naloxone on cognitive function in rats with vascular dementia (VD). METHODS: Vascular dementia was established by permanent occlusion of the common carotid arteries. Rats were divided into three groups viz., sham-operated controls, naloxone treated VD rats (naloxone 0.8 mg/kg, i.p. daily for 7 days), and nontreated VD rats. The Morris water maze test was performed to study spatial learning and memory. The extracellular recording technique was used to record long-term potentiation (LTP) of the Schaffer collateral-CA1 synapse in the rat hippocampal slices. RESULTS: In the hidden platform trials, escape latencies of the naloxone treated VD rats were significantly shorter than that of the nontreated VD rats (P < 0.001). In the probe trials, the number of enteries in the target area of the naloxone treated VD rats (8.36 +/- 1.38 times/min) were more than that of the nontreated VD rats (4.64 +/- 1.73 times/min) (P < 0.01). The magnitudes of LTP recorded in the CA1 pyramidal neurons of the naloxone treated VD rats were significantly augmented when compared to the nontreated VD rats (P < 0.05). INTERPRETATION & CONCLUSION: Naloxone could facilitate spatial learning and memory and enhance LTP in the CA1 region of hippocampus in rats with VD. It is postulated that naloxone might exert beneficial effects on cognitive function in VD in rats by modulating the synaptic plasticity in the hippocampal neuronal network.
Subject(s)
Animals , Cognition/drug effects , Dementia, Vascular/drug therapy , Electrophysiology , Hippocampus/cytology , Humans , Long-Term Potentiation/physiology , Maze Learning/drug effects , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Rats , Time FactorsABSTRACT
Bilateral aspiration lesions of the fimbria-fornix were performed in 10 male Sprague Dawley rats weighing 240-300 g under chloral hydrate narcose (420 mg/kg). Another 9 animals were operated in the same way, but no aspiration was carried out to constitute a control group. A week after surgery recording and stimulation electrodes were lowered to the dentate gyrus and the perforant path respectively, using the same narcose. After tetanic stimulation (10 trains at 400 Hz) a potentiation of the population spike develops in both groups, but the slope of the excitatory postsynaptic potential showed no potentiation in the lesioned group. Acetylcholinesterase histochemistry confirmed a severe reduction of the cholinergic innervation to the hippocampal formation, suggesting a causal relationship to the deficits seen in long-term potentiation. This impaired potentiation could be related to the memory deficits reported for fimbria-fornix lesioned rats. Such pattern of potentiation deviates from what has been described for aged, memory deficient rats, but closely corresponds to the changes described in infantile rats