Efficacy of invasive and non-invasive methods for the treatment of Parkinson's disease: Nanodelivery and enriched environment.

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterised by the loss of dopaminergic neurons in the substantia nigra pars compacta and the subsequent motor disability. The most frequently used treatments in clinics, such as L-DOPA, restore dopaminergic neurotransmission in the brain. However, these treatments are only symptomatic, have temporary efficacy, and produce side effects.

Effects of curcumin nanodelivery on schizophrenia and glioblastoma.

Curcumin is a natural polyphenol, which has a variety of pharmacological activities, including, antineoplastic, antioxidative and neuroprotective effects. Recent studies provided evidence for the bioactive role of curcumin in the prevention and treatment of various central nervous system (CNS)-related diseases including Parkinson's, Alzheimer's, Schizophrenia disease and glioma neoplasia. Schizophrenia is a disabling psychiatric disorder related with an aberrant functional coupling between hippocampus and prefrontal cortex that might be crucial for cognitive dysfunction.

Enriched environment as a nonpharmacological neuroprotective strategy.

The structure and functions of the central nervous system are influenced by environmental stimuli, which also play an important role in brain diseases. Enriched environment (EE) consists of producing modifications in the environment of standard laboratory animals to induce an improvement in their biological conditions. This paradigm promotes transcriptional and translational effects that result in ameliorated motor, sensory, and cognitive stimulation.

The role of ketamine in major depressive disorders: Effects on parvalbumin-positive interneurons in hippocampus.

Major depressive disorder (MDD) is a complex illness that is arising as a growing public health concern. Although several brain areas are related to this type of disorders, at the cellular level, the parvalbumin-positive cells of the hippocampus interplay a very relevant role. They control pyramidal cell bursts, neuronal networks, basic microcircuit functions, and other complex neuronal tasks involved in mood disorders.

Murine femur micro-computed tomography and biomechanical datasets for an ovariectomy-induced osteoporosis model.

The development of new effective and safer therapies for osteoporosis, in addition to improved diagnostic and prevention strategies, represents a serious need in the scientific community. Micro-CT image-based analyses in association with biomechanical testing have become pivotal tools in identifying osteoporosis in animal models by assessment of bone microarchitecture and resistance, as well as bone strength. Here, we describe a dataset of micro-CT scans and reconstructions of 15 whole femurs and biomechanical tests on contralateral femurs from C57BL/6JOlaHsd ovariectomized (OVX), resembling human post-menopausal osteoporosis, and sham operated (sham) female mice.

The effect of 5-HT receptor agonists on the entopeduncular nucleus is modified in 6-hydroxydopamine-lesioned rats.

Background And Purpose: l-DOPA prolonged treatment leads to disabling motor complications as dyskinesia that could be decreased by drugs acting on 5-HT receptors. Since the internal segment of the globus pallidus, homologous to the entopeduncular nucleus in rodents, seems to be involved in the etiopathology of l-DOPA-induced dyskinesia, we investigated whether the entopeduncular nucleus is modulated by the 5-HT receptor partial and full agonists, buspirone, and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) in control and 6-hydroxydopamine (6-OHDA)-lesioned rats with or without long-term l-DOPA treatment.

Experimental Approach: Extracellular single-unit electrocorticogram and local field potential recordings under anaesthesia, immunostaining assays and optogenetic manipulation coupled to electrophysiological recordings were performed.

6-Hydroxydopamine lesion and levodopa treatment modify the effect of buspirone in the substantia nigra pars reticulata.

Background And Purpose: l-DOPA-induced dyskinesia (LID) is considered a major complication in the treatment of Parkinson's disease (PD). Buspirone (5-HT partial agonist) have shown promising results in the treatment of PD and LID, however no 5-HT-based treatment has been approved in PD. The present study was aimed to investigate how the substantia nigra pars reticulata (SNr) is affected by buspirone and whether it is a good target to study 5-HT antidyskinetic treatments.

Enriched Environment Reverts Somatostatin Interneuron Loss in MK-801 Model of Schizophrenia.

Dysregulation of the inhibitory drive has been proposed to be a central mechanism to explain symptoms and pathophysiological hallmarks in schizophrenia. A number of recent neuroanatomical studies suggest that certain types of inhibitory cells are deficient in schizophrenia, including somatostatin-immunoreactive interneurons (SST+). The present study sought to use stereological methods to investigate whether the number of SST+ interneurons decreased after repeated injections of NMDA receptor antagonist MK-801 (0.

Therapeutic potential of cannabinoids as neuroprotective agents for damaged cells conducing to movement disorders.

The basal ganglia (BG), an organized network of nuclei that integrates cortical information, play a crucial role in controlling motor function. In fact, movement disorders such as Parkinson's disease (PD) and Huntington's disease (HD) are caused by the degeneration of specific structures within the BG. There is substantial evidence supporting the idea that cannabinoids may constitute novel promising compounds for the treatment of movement disorders as neuroprotective and anti-inflammatory agents.

Effects of adult enriched environment on cognition, hippocampal-prefrontal plasticity and NMDAR subunit expression in MK-801-induced schizophrenia model.

Schizophrenia is a mental disorder characterized by psychosis, negative symptoms and cognitive impairment. Cognitive deficits are enduring and represent the most disabling symptom but are currently poorly treated. N-methyl D-aspartate receptor (NMDAR) hypofunction hypothesis has been notably successful in explaining the pathophysiological findings and symptomatology of schizophrenia.

High-Altitude Cognitive Impairment Is Prevented by Enriched Environment Including Exercise via VEGF Signaling.

Exposure to hypobaric hypoxia at high altitude (above 2500 m asl) causes cognitive impairment, mostly attributed to changes in brain perfusion and consequently neuronal death. Enriched environment and voluntary exercise has been shown to improve cognitive function, to enhance brain microvasculature and neurogenesis, and to be neuroprotective. Here we show that high-altitude exposure (3540 m asl) of Long Evans rats during early adulthood (P48-P59) increases brain microvasculature and neurogenesis but impairs spatial and visual memory along with an increase in neuronal apoptosis.

Correction to: Deleterious Effects of VEGFR2 and RET Inhibition in a Preclinical Model of Parkinson's Disease.

The authors found a terrible mistake in the manuscript. The legends from the Fig. 5 and 6 are interchanged.

Nanoformulation: A Useful Therapeutic Strategy for Improving Neuroprotection and the Neurorestorative Potential in Experimental Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, but current therapies are only symptomatic. Experimental models are necessary to go deeper in the comprehension of pathophysiological mechanism and to assess new therapeutic strategies. The unilateral 6-hydroxydopamine (6-OHDA) lesion either in medial forebrain bundle (MFB) or into the striatum in rats affords to study various stages of PD depending on the evolution time lapsed.

Erratum to: Short-Term Exposure to Enriched Environment in Adult Rats Restores MK-801-Induced Cognitive Deficits and GABAergic Interneuron Immunoreactivity Loss.

The original version of this article unfortunately contained a mistake. The name of author was changed from "Pascual Gargiulo" to "Pascual Ángel Gargiulo.

Environmental Enrichment Reverses Tyrosine Kinase Inhibitor-Mediated Impairment Through BDNF-TrkB Pathway.

Exposure to an enriched environment (EE) has neuroprotective benefits and improves recovery from brain injury due to, among other, increased neurotrophic factor expression. Through these neurotrophins, important cortical and hippocampal changes occur. Vandetanib acts as a tyrosine kinase inhibitor of cell receptors, among others, the vascular endothelial growth factor receptor (VEGFR).

Deleterious Effects of VEGFR2 and RET Inhibition in a Preclinical Model of Parkinson's Disease.

Neurotrophic factors (NTFs) are a promising therapeutic option for Parkinson's disease (PD). They exert their function through tyrosine kinase receptors. Our goal was to assess the effects of administering a selective tyrosine kinase inhibitor (vandetanib) that blocks VEGFR2 and RET receptors in a preclinical model of PD.

Short-Term Exposure to Enriched Environment in Adult Rats Restores MK-801-Induced Cognitive Deficits and GABAergic Interneuron Immunoreactivity Loss.

Perinatal injections of N-methyl-D-aspartate (NMDA) receptor antagonist in rodents emulate some cognitive impairments and neurochemical alterations, such as decreased GABAergic (gamma aminobutyric acid) interneuron immunoreactivity, also found in schizophrenia. These features are pervasive, and developing neuroprotective or neurorestorative strategies is of special interest. In this work, we aimed to investigate if a short exposure to enriched environment (EE) in early adulthood (P55-P73) was an effective strategy to improve cognitive dysfunction and to restore interneuron expression in medial prefrontal cortex (mPFC) and hippocampus (HPC).

Morphological Changes in a Severe Model of Parkinson's Disease and Its Suitability to Test the Therapeutic Effects of Microencapsulated Neurotrophic Factors.

The unilateral 6-hydroxydopamine (6-OHDA) lesion of medial forebrain bundle (MFB) in rats affords us to study the advanced stages of Parkinson's disease (PD). Numerous evidences suggest synergic effects when various neurotrophic factors are administered in experimental models of PD. The aim of the present work was to assess the morphological changes along the rostro-caudal axis of caudo-putamen complex and substantia nigra (SN) in the referred model in order to test the suitability of a severe model to evaluate new neurorestorative therapies.

Topographical Distribution of Morphological Changes in a Partial Model of Parkinson's Disease--Effects of Nanoencapsulated Neurotrophic Factors Administration.

Administration of various neurotrophic factors is a promising strategy against Parkinson's disease (PD). An intrastriatal infusion of 6-hydroxidopamine (6-OHDA) in rats is a suitable model to study PD. This work aims to describe stereological parameters regarding rostro-caudal gradient, in order to characterize the model and verify its suitability for elucidating the benefits of therapeutic strategies.

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson's disease.

Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release.

Increased physical activity is not enough to recover astrocytic population from dark-rearing. Synergy with multisensory enrichment is required.

Elimination of sensory inputs (deprivation) modifies the properties of the sensory cortex and serves as a model for studying plasticity during postnatal development. Many studies on the effects of deprivation have been performed in the visual cortex using dark-rearing as a visual deprivation model. It induces changes in all cellular and molecular components, including astrocytes, which play an important role in the development, maintenance, and plasticity of the cortex, mediated by cytokines which have been termed angioglioneurins.

VEGF reverts the cognitive impairment induced by a focal traumatic brain injury during the development of rats raised under environmental enrichment.

The role of VEGF in the nervous system is extensive; apart from its angiogenic effect, VEGF has been described as a neuroprotective, neurotrophic and neurogenic molecule. Similar effects have been described for enriched environment (EE). Moreover, both VEGF and EE have been related to improved spatial memory.

Angiogenic signalling pathways altered in gliomas: selection mechanisms for more aggressive neoplastic subpopulations with invasive phenotype.

The angiogenesis process is a key event for glioma survival, malignancy and growth. The start of angiogenesis is mediated by a cascade of intratumoural events: alteration of the microvasculature network; a hypoxic microenvironment; adaptation of neoplastic cells and synthesis of pro-angiogenic factors. Due to a chaotic blood flow, a consequence of an aberrant microvasculature, tissue hypoxia phenomena are induced.

Enriched and deprived sensory experience induces structural changes and rewires connectivity during the postnatal development of the brain.

During postnatal development, sensory experience modulates cortical development, inducing numerous changes in all of the components of the cortex. Most of the cortical changes thus induced occur during the critical period, when the functional and structural properties of cortical neurons are particularly susceptible to alterations. Although the time course for experience-mediated sensory development is specific for each system, postnatal development acts as a whole, and if one cortical area is deprived of its normal sensory inputs during early stages, it will be reorganized by the nondeprived senses in a process of cross-modal plasticity that not only increases performance in the remaining senses when one is deprived, but also rewires the brain allowing the deprived cortex to process inputs from other senses and cortices, maintaining the modular configuration.

Effect of intracortical vascular endothelial growth factor infusion and blockade during the critical period in the rat visual cortex.

VEGF is the major angiogenic and vascular permeability factor in health and disease. Vascular development depends on function, and in sensory areas is experience-dependent. Our aim was to investigate, qualitatively and quantitatively, the effects of intracortical infusion and neutralisation of VEGF during the first days of the critical visual period, when peak levels of endogenous VEGF secretion are reached.