Modification of pre-ictal cortico-hippocampal oscillations by medial ganglionic eminence precursor cells grafting in the pilocarpine model of epilepsy.

Cell replacement therapies using medial ganglionic eminence (MGE)-derived GABAergic precursors reduce seizures by restoring inhibition in animal models of epilepsy. However, how MGE-derived cells affect abnormal neuronal networks and consequently brain oscillations to reduce ictogenesis is still under investigation. We performed quantitative analysis of pre-ictal local field potentials (LFP) of cortical and hippocampal CA1 areas recorded in vivo in the pilocarpine rat model of epilepsy, with or without intrahippocampal MGE-precursor grafts (PILO and PILO+MGE groups, respectively).

Bradykinin promotes immune responses in differentiated embryonic neurospheres carrying APP and PS1 mutations.

Background: Neural progenitor cells (NPCs) can be cultivated from developing brains, reproducing many of the processes that occur during neural development. They can be isolated from a variety of animal models, such as transgenic mice carrying mutations in amyloid precursor protein (APP) and presenilin 1 and 2 (PSEN 1 and 2), characteristic of familial Alzheimer's disease (fAD). Modulating the development of these cells with inflammation-related peptides, such as bradykinin (BK) and its antagonist HOE-140, enables the understanding of the impact of such molecules in a relevant AD model.

Differentiated Embryonic Neurospheres from Familial Alzheimer's Disease Model Show Innate Immune and Glial Cell Responses.

Proteins involved in the Alzheimer's disease (AD), such as amyloid precursor protein (APP) and presenilin-1 (PS1), play critical roles in early development of the central nervous system (CNS), as well as in innate immune and glial cell responses. Familial AD is associated with the presence of APP and PS1 mutations. However, it is still unknown whether these mutations cause deficits in CNS development of carriers.

Neuroprotective effects of resistance physical exercise on the APP/PS1 mouse model of Alzheimer's disease.

Introduction: Physical exercise has beneficial effects by providing neuroprotective and anti-inflammatory responses to AD. Most studies, however, have been conducted with aerobic exercises, and few have investigated the effects of other modalities that also show positive effects on AD, such as resistance exercise (RE). In addition to its benefits in developing muscle strength, balance and muscular endurance favoring improvements in the quality of life of the elderly, RE reduces amyloid load and local inflammation, promotes memory and cognitive improvements, and protects the cortex and hippocampus from the degeneration that occurs in AD.

The effects of resistance exercise on cognitive function, amyloidogenesis, and neuroinflammation in Alzheimer's disease.

With the increasing prevalence of Alzheimer's disease (AD) and difficulties in finding effective treatments, it is essential to discover alternative therapies through new approaches. In this regard, non-pharmacological therapies, such as physical exercise, have been proposed and explored for the treatment of AD. Recent studies have suggested that resistance exercise (RE) is an effective strategy for promoting benefits in memory and cognitive function, producing neuroprotective and anti-inflammatory effects, and reducing amyloid load and plaques, thereby reducing the risk, and alleviating the neurodegeneration process of AD and other types of dementia in the elderly.

Purinergic signaling in cognitive impairment and neuropsychiatric symptoms of Alzheimer's disease.

About 10 million new cases of dementia develop worldwide each year, of which up to 70% are attributable to Alzheimer's disease (AD). In addition to the widely known symptoms of memory loss and cognitive impairment, AD patients frequently develop non-cognitive symptoms, referred to as behavioral and psychological symptoms of dementia (BPSDs). Sleep disorders are often associated with AD, but mood alterations, notably depression and apathy, comprise the most frequent class of BPSDs.

AAV-mediated neuronal expression of an scFv antibody selective for Aβ oligomers protects synapses and rescues memory in Alzheimer models.

The accumulation of soluble oligomers of the amyloid-β peptide (AβOs) in the brain has been implicated in synapse failure and memory impairment in Alzheimer's disease. Here, we initially show that treatment with NUsc1, a single-chain variable-fragment antibody (scFv) that selectively targets a subpopulation of AβOs and shows minimal reactivity to Aβ monomers and fibrils, prevents the inhibition of long-term potentiation in hippocampal slices and memory impairment induced by AβOs in mice. As a therapeutic approach for intracerebral antibody delivery, we developed an adeno-associated virus vector to drive neuronal expression of NUsc1 (AAV-NUsc1) within the brain.

Clozapine prevented social interaction deficits and reduced c-Fos immunoreactivity expression in several brain areas of rats exposed to acute restraint stress.

In the present study, we evaluate the effect of acute restraint stress (15 min) of male Wistar rats on social interaction measurements and c-Fos immunoreactivity (c-Fos-ir) expression, a marker of neuronal activity, in areas involved with the modulation of acute physical restraint in rats, i.e., the paraventricular nucleus of the hypothalamus (PVN), median raphe nucleus (MnR), medial prefrontal cortex (mPFC), cingulate prefrontal cortex (cPFC), nucleus accumbens (NaC), hippocampus (CA3), lateral septum (LS) and medial amygdala (MeA).

Intravenous infusion of bone marrow mononuclear cells promotes functional recovery and improves impaired cognitive function via inhibition of Rho guanine nucleotide triphosphatases and inflammatory signals in a model of chronic epilepsy.

Temporal lobe epilepsy is the most common form of intractable epilepsy in adults. More than 30% of individuals with epilepsy have persistent seizures and have drug-resistant epilepsy. Based on our previous findings, treatment with bone marrow mononuclear cells (BMMC) could interfere with early and chronic phase epilepsy in rats and in clinical settings.

Resistance Exercise Decreases Amyloid Load and Modulates Inflammatory Responses in the APP/PS1 Mouse Model for Alzheimer's Disease.

Neuroinflammation has been shown to play a crucial role in the development of Alzheimer's disease (AD) and also has an association with amyloid-β (Aβ) plaques, a hallmark of this disease. Physical exercise has emerged as an alternative treatment for pathological impairment in AD. In light of this evidence, together with the fact that the hippocampus is one of the first structures to be affected in AD, we analyzed hippocampal changes in Aβ load, inflammatory responses, and locomotor activity in transgenic APP/PS1 mouse model for AD submitted to a resistance exercise (RE) program.

Transplantation of inhibitory precursor cells from medial ganglionic eminence produces distinct responses in two different models of acute seizure induction.

Medial ganglionic eminence (MGE) is one of the sources of inhibitory interneurons during development. Following transplantation in postnatal developing brain, MGE cells can increase local inhibition suggesting a possible protection to GABAergic dysfunction in brain disorders, such as epilepsy. Since it has been shown that MGE-derived cells harvested as neurospheres are able to suppress seizures, it might be important to investigate whether these protective effects would change in different seizure models.

Post-sensitization treatment with rimonabant blocks the expression of cocaine-induced behavioral sensitization and c-Fos protein in mice.

CB1 receptor antagonists have been shown to prevent acute and long-term behavioral effects of cocaine. Here we evaluate the effectiveness of the CB1 receptor antagonist rimonabant to modify sensitized responses to cocaine. Mice were treated with saline or cocaine injections in a 15-day intermittent sensitization treatment and subsequently treated with either vehicle, 1 or 10mg/kg rimonabant in the drug-associated environment for 8 consecutive days.

Maternal deprivation alters growth, food intake, and neuropeptide Y in the hypothalamus of adolescent male and female rats.

Maternal deprivation (MD) for 24 hr during the neonatal period impairs body weight gain in adolescent and adult rats. It has been previously shown that maternally deprived rats consume less standard and carbohydrate-rich diets. Because neuropeptide Y (NPY) is implicated in feeding behavior, we assessed, prospectively, the effects of maternal deprivation, imposed on postnatal days (PND) 3 (DEP3) or 11 (DEP11), on physical development (snout-anal length and body weight gain, measured once a week) and food intake (assessed daily, during the rest and active phases, from PND 23 to PND 51); NPY-immunoreactivity (NPY-ir) in the arcuate nucleus of the hypothalamus was evaluated in male (at PND 52) and female rats in estrous (at PND 53-60).

Manganese-Enhanced MRI: Biological Applications in Neuroscience.

Magnetic resonance imaging (MRI) is an excellent non-invasive tool to investigate biological systems. The administration of the paramagnetic divalent ion manganese (Mn(2+)) enhances MRI contrast in vivo. Due to similarities between Mn(2+) and calcium (Ca(2+)), the premise of manganese-enhanced MRI (MEMRI) is that the former may enter neurons and other excitable cells through voltage-gated Ca(2+) channels.

Participation of bone marrow-derived cells in hippocampal vascularization after status epilepticus.

Purpose: Diseases such as temporal lobe epilepsy, brain trauma and stroke can induce endothelial cell proliferation and angiogenesis in specific brain areas. During status epilepticus (SE), bone marrow-derived cells are able to infiltrate and proliferate, dramatically increasing at the site of injury. However, it is still unclear whether these cells directly participate in vascular changes induced by SE.

Atypical antipsychotic olanzapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of dizocilpine (MK-801) into the inferior colliculus in rats.

Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). MK-801 is an NMDA receptor-antagonist known to produce hyperactivity, deficits in prepulse inhibition and social withdrawal, behaviors which correlate well with some of the positive, cognitive and negative symptoms of schizophrenia.

Anticonvulsant activity of bone marrow cells in electroconvulsive seizures in mice.

Background: Bone marrow is an accessible source of progenitor cells, which have been investigated as treatment for neurological diseases in a number of clinical trials. Here we evaluated the potential benefit of bone marrow cells in protecting against convulsive seizures induced by maximum electroconvulsive shock (MES), a widely used model for screening of anti-epileptic drugs. Behavioral and inflammatory responses were measured after MES induction in order to verify the effects promoted by transplantation of bone marrow cells.

Effect of the bone marrow cell transplantation on elevated plus-maze performance in hippocampal-injured mice.

Several reports have shown that the hippocampus plays an important role in different aspects of the emotional control. There is evidence that lesions in this structure cause behavioral disinhibition, with reduction of reactions expressing fear and anxiety. Thus, to portray the aptitude of cell therapy to abrogate injuries of hippocampal tissue, we examined the behavioral effects of bone marrow mononuclear cells (BMMCs) transplantation on C57BL/6 mice that had the hippocampus damaged by electrolytic lesion.

Manganese-enhanced magnetic resonance imaging in the acute phase of the pilocarpine-induced model of epilepsy.

Magnetic resonance images are useful in the study of experimental models of temporal lobe epilepsy. The manganese-enhanced MRI (MEMRI) technique is of interest since it combines the effects caused by manganese on the increased contrast in activated cell populations, when competing with calcium in synaptic transmission. Thus, the purpose of this study was to investigate the temporal evolution of the contrast related to manganese in the acute phase of temporal lobe epilepsy induced by systemic pilocarpine and compare it to the expression of the c-Fos protein.

Behavioral changes resulting from the administration of cycloheximide in the pilocarpine model of epilepsy.

Cycloheximide influences synaptic reorganization resulting from pilocarpine-induced status epilepticus (SE). To investigate the possible behavioral consequences of this effect, we subjected animals to pilocarpine-induced SE either in the absence (Pilo group) or presence of cycloheximide (Chx group). Animals were further divided regarding the occurrence of spontaneous recurrent seizures (SRS).