Search

Oxidative stress (OS) is defined as the imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system. Living organisms produce ROS from molecular oxygen as a consequence of normal cellular metabolism. In order to prevent damage, cells have an antioxidant defense system constituted by an enzymatic component (including catalases, superoxide dismutases, etc.) and nonenzymatic antioxidants component (glutathione, α-tocopherol, ascorbic acid, etc.). When the levels of ROS exceed cell capacity, it can cause damage in cellular components such as carbohydrates, nucleic acids, lipids, and proteins, thus altering their function. Whenever this imbalance occurs within the central nervous system, it can lead to the development of the neurodegenerative disorders. Neurodegenerative diseases are characterized by the loss of neuronal cells and, in most cases, by the aggregates of proteins that form intracytoplasmic and intranuclear inclusions in neurons and glial cells. Data on the literature show that there are two possible mechanisms involved in most of neurodegenerative diseases: (1) mutations and/or aggregation of characteristic proteins of each disease such as α-synuclein in Parkinson’s disease (PD) or beta-amyloid peptide in Alzheimer’s disease (AD) and (2) dysfunction of mitochondrial energy metabolism in neurons. In this section, we will focus on this last one., Instituto de Investigaciones Bioquímicas de La Plata

Oxidative stress (OS) is defined as the imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system. Living organisms produce ROS from molecular oxygen as a consequence of normal cellular metabolism. In order to prevent damage, cells have an antioxidant defense system constituted by an enzymatic component (including catalases, superoxide dismutases, etc.) and nonenzymatic antioxidants component (glutathione, α-tocopherol, ascorbic acid, etc.). When the levels of ROS exceed cell capacity, it can cause damage in cellular components such as carbohydrates, nucleic acids, lipids, and proteins, thus altering their function. Whenever this imbalance occurs within the central nervous system, it can lead to the development of the neurodegenerative disorders. Neurodegenerative diseases are characterized by the loss of neuronal cells and, in most cases, by the aggregates of proteins that form intracytoplasmic and intranuclear inclusions in neurons and glial cells. Data on the literature show that there are two possible mechanisms involved in most of neurodegenerative diseases: (1) mutations and/or aggregation of characteristic proteins of each disease such as α-synuclein in Parkinson’s disease (PD) or beta-amyloid peptide in Alzheimer’s disease (AD) and (2) dysfunction of mitochondrial energy metabolism in neurons. In this section, we will focus on this last one. Instituto de Investigaciones Bioquímicas de La Plata

La enfermedad de Parkinson es una enfermedad neurodegenerativa de las neuronas dopaminérgicas de la vía nigrosestriatal. Es considerada de índole multifactorial debido a la multiplicidad de síntomas que experimentan los pacientes, los cuales pueden agruparse por su afección de las vías motoras y/o de las vías mesolímibicas. Si bien esta patología es conocida por sus déficits motores característicos, los pacientes también presentan una amplia variedadde síntomas no motores, como deterioro del aprendizaje y la memoria, depresión, problemas gastrointestinales, entre otros, que afectan severamente su calidad de vida. Estos síntomas no motores resultan de una disfunción de sistemas interconectados, que incluyen al cuerpo estriado, la neocorteza y el hipocampo y de los diferentes circuitos glutamatérgicos involucrados en la modulación de la plasticidad sináptica. Es por esto que la presente revisión busca profundizar el conocimiento actual en relación al deterioro cognitivo asociado a la patología parkinsoniana para lograr un mejor entendimiento de los cambios neuronales, a nivel molecular, químico y fisiológico, principalmente en el hipocampo. El conocimiento de estos mecanismos no motores participantes en la EP podrían resultar en un potencial enfoque de nuevas estrategias terapéuticas., Parkinson’s disease is a neurodegenerative disorder that results from a progressive dopaminergic neuronal loss. It is considered a multifactorial condition due to the multiplicity of symptoms experienced by patients, which can be grouped by their disturbance in motor pathways and / or mesolímibics pathways. While this condition is known for its characteristic motor deficits, patients also have a wide variety of non-motor symptoms, such as impaired learning and memory, depression, gastrointestinal problems, among others, which severely affect their quality of life. These non-motor symptoms result from dysfunction of interconnected systems, including the striatum, the neocortex and the hippocampus and the different glutamatergic circuits involved in synaptic plasticity modulation. This review seeks to deepen the current knowledge regarding to cognitive impairment associated with parkinsonian pathology for a better understanding of the neural changes at molecular, chemical and physiological level, mainly in the hippocampus. Knowledge of these mechanisms involved in non-motor PD could result in potential new therapeutic strategies., Facultad de Ciencias Médicas, Instituto de Investigaciones Bioquímicas de La Plata

In the current study we implemented ICV IGF-1 gene therapy in very old rats (28 months) and assessed the motor performance pre and 17-days after surgery. Glial immunoreactivity in striatum was evaluated by Iba1 and GFAP markers., Facultad de Ciencias Médicas

Microglial cells play an important role in healthy and diseased brain removing apoptotic neurons (Perry et al., 1985; Ashwell, 1990; Calderó et al., 2009; Sierra et al., 2010), establishing transient connections with neuronal synapses (Wake et al., 2009) and producing neurotrophic factors that modulate neurogenesis during embryogenesis and adulthood (Ueno et al., 2013; Xia et al., 2015).These cells are essential for ensuring neuroprotection in the normal and pathological condition of central nervous system as they are an important sources of neurotrophic factors. It has been described that aging reduces the ability of microglia to provide neuroprotection (Streit and Xue, 2014; Floden and Combs, 2011; Harry, 2013, Orre et al., 2014, Suh et al., 2013). Microglia-mediated neuroprotection has been described in the nervous system (Polazzi and Contestabile, 2002; Lai and Todd, 2008). Several studies have shown that, after axotomy of the motor axons of the facial nerve, the injured neurons regenerate when activated microglial cells are present (reviewed in Raivich, 2002), being the activation of microglia crucial for the regeneration to happen. Moreover, transplantation studies showing that engraftment of cultured microglial cells into the injured spinal cord promotes neurite growth into such microglial grafts (Rabchevsky and Streit, 1997) support this idea that microglial neuroinflammation is a vital component of the regenerative process. Previous studies of our group described that intracerebroventricular (ICV) Insulin-like growth factor-I (IGF-I) gene therapy induced a significant improvement in motor performance in aged rats (Sanchez et al., 2008, Nishida et al., 2011). Several works report that IGF-I stimulates microglia proliferation (O’Donnell et al., 2002;). We propose that restorative effects of IGF-I in motor skills could be mediated by glial cells. In the current study we implemented ICV IGF-I gene therapy in very old rats (28 months) and assessed the motor performance pre and 17-days after surgery. Glial immunoreactivity in striatum was evaluated by Iba1 and GFAP markers. Results: As we previously reported, IGF-I restored motor coordination and forelimb grip strength in aged rats (Sanchez et al., 2008). We found that microglia immunoreactivity (Iba-1+) was significantly increased for at least 17 days after treatment with IGF-I (Xm-senil-IGF-I=8.370±0.3297 vs Xm-senil-DsRed= 5.557±0.2553; p

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder which manifests as a motor disorder, characterized by slowness of movements, rigidity and tremor. Motor dysfunction of PD is due to dopamine loss in the neostriatum and due to the neurodegeneration of dopaminergic neuron’s cell bodies of the Substantia Nigra Pars Compacta (SNPC). Evidence suggests that chronic neuroinflammation, mediated by activated microglial and astroglial cells in the SNPC, could be essential for the degenerative process. It is well known that IGF1 plays a key role in neuroprotection in physiological conditions, both in health and disease. Previous studies of our group have shown that Rad-IGF ICV gene therapy had a restorative effect on motor skills of aged rats., Facultad de Ciencias Exactas