Sat Jul 27, 2013 1:29 pm by 
Autism is a neurodevelopmental disorder characterized by significant impairments in social, behavioral and communicative functions. Current evidence suggests that neurobiological abnormalities in autism are associated with changes in cytoarchitectural and neuronal organization that may be determined by genetic, environmental, immunological and toxic factors. Neuropathological studies have shown that cytoarchitectural organizational abnormalities of the cerebral cortex, cerebellum and other subcortical structures as well as a reduction in the number of cortical minicolumns appear to be the most prominent morphological changes in autism.
The main goal of our research on autism is to determine the role of neuroglia (astrocytes and microglia) and immune mediated responses in pathogenic mechanisms responsible for autism.
Neuroglia such as astrocytes and microglia, along with perivascular macrophages and endothelial cells, play important roles in neuronal function and homeostasis. Neuroglial cells also have a number of crucial roles in the regulation of the CNS immune responses. Astrocytes, for example, are important in the detoxification of excess excitatory amino acids, integrity of the blood brain barrier, production of neurotrophic factors and play a fundamental role in the metabolism of glutamate. In normal homeostatic stages, astrocytes facilitate neuronal survival by production of growth factors, and uptake/removal of excitotoxic neurotransmitters, such as glutamate, from the synaptic microenvironment. However, during stages of astroglial activation secondary to injury or in response to neuronal dysfunction, astrocytes can produce several factors that may modulate inflammatory responses. Astrocytes can secrete pro-inflammatory cytokines, chemokines and metalloproteinases that may contribute to the magnification of immune reactions within the CNS. Similarly, microglial activation is an important factor in the neuroglial responses to injury or dysfunction. Microglia participate in processes of synaptic stripping, cortical plasticity and immune surveillance. In several neurological disorders such as Alzheimer's disease, HIV dementia, epilepsy and multiple sclerosis, astroglial and microglial responses are prominent and appear to mediate important mechanisms that lead to neuronal dysfunction. In HIV dementia for example, microglial activation and infiltration by macrophages participate in the mechanisms of neuronal damage responsible for the dementia. In other disorders such as epilepsy and particularly in Rasmussen's syndrome, a rare pediatric epileptic disorder, both astroglial and microglial reactions occur in parallel with T cell infiltration. Changes in astroglia and microglia can therefore produce marked neuronal dysfunction that is likely to be associated with mechanisms of seizure activity.
Why study neuroglial and immune reactions in autism?
Current evidence suggests that neurobiological abnormalities in autism are associated with changes in cytoarchitectural and neuronal organization that may be determined by genetic, environmental, immunological and toxic factors. Since neuroglia have central roles during brain development, cortical organization, neuronal function and immune responses, we hypothesize that neuroglia may contribute to the pathogenesis of autism in several ways:
Neuroglia may be dysfunctional during the process of neuronal organization and plasticity of cortical and subcortical structures, a change that may contribute to the neuropathological abnormalities observed in autism.
Neuroglia may react to extrinsic factors, such as systemic immune responses, toxins or infections, and produce disturbances in the CNS microenvironment that facilitate the development of immune mediated reactions.
Abnormal neuroglial activation may be present in autistic patients due to genetic susceptibility to inflammation, a change that can lead to abnormalities in neuronal-neuroglial interactions.
Neuroglial activation can trigger the development of cellular or humoral immune responses that lead to neuronal/neuroglial dysfunction.
Systemic immune responses may trigger abnormal pathogenic reactions in neuroglia.
Our experimental approaches include study of brain tissues obtained from patients with autism, determination of the profile of cytokines and chemokines and characterization of immune mediated reactions in cortical and subcortical regions of autistic brains. Further understanding of the role of neuroglia and immune reactions in the neurobiology of autism may contribute to the design of therapeutic interventions that minimize the neurological and behavioral abnormalities that occur in this disease.
The main goal of our research on autism is to determine the role of neuroglia (astrocytes and microglia) and immune mediated responses in pathogenic mechanisms responsible for autism.
Neuroglia such as astrocytes and microglia, along with perivascular macrophages and endothelial cells, play important roles in neuronal function and homeostasis. Neuroglial cells also have a number of crucial roles in the regulation of the CNS immune responses. Astrocytes, for example, are important in the detoxification of excess excitatory amino acids, integrity of the blood brain barrier, production of neurotrophic factors and play a fundamental role in the metabolism of glutamate. In normal homeostatic stages, astrocytes facilitate neuronal survival by production of growth factors, and uptake/removal of excitotoxic neurotransmitters, such as glutamate, from the synaptic microenvironment. However, during stages of astroglial activation secondary to injury or in response to neuronal dysfunction, astrocytes can produce several factors that may modulate inflammatory responses. Astrocytes can secrete pro-inflammatory cytokines, chemokines and metalloproteinases that may contribute to the magnification of immune reactions within the CNS. Similarly, microglial activation is an important factor in the neuroglial responses to injury or dysfunction. Microglia participate in processes of synaptic stripping, cortical plasticity and immune surveillance. In several neurological disorders such as Alzheimer's disease, HIV dementia, epilepsy and multiple sclerosis, astroglial and microglial responses are prominent and appear to mediate important mechanisms that lead to neuronal dysfunction. In HIV dementia for example, microglial activation and infiltration by macrophages participate in the mechanisms of neuronal damage responsible for the dementia. In other disorders such as epilepsy and particularly in Rasmussen's syndrome, a rare pediatric epileptic disorder, both astroglial and microglial reactions occur in parallel with T cell infiltration. Changes in astroglia and microglia can therefore produce marked neuronal dysfunction that is likely to be associated with mechanisms of seizure activity.
Why study neuroglial and immune reactions in autism?
Current evidence suggests that neurobiological abnormalities in autism are associated with changes in cytoarchitectural and neuronal organization that may be determined by genetic, environmental, immunological and toxic factors. Since neuroglia have central roles during brain development, cortical organization, neuronal function and immune responses, we hypothesize that neuroglia may contribute to the pathogenesis of autism in several ways:
Neuroglia may be dysfunctional during the process of neuronal organization and plasticity of cortical and subcortical structures, a change that may contribute to the neuropathological abnormalities observed in autism.
Neuroglia may react to extrinsic factors, such as systemic immune responses, toxins or infections, and produce disturbances in the CNS microenvironment that facilitate the development of immune mediated reactions.
Abnormal neuroglial activation may be present in autistic patients due to genetic susceptibility to inflammation, a change that can lead to abnormalities in neuronal-neuroglial interactions.
Neuroglial activation can trigger the development of cellular or humoral immune responses that lead to neuronal/neuroglial dysfunction.
Systemic immune responses may trigger abnormal pathogenic reactions in neuroglia.
Our experimental approaches include study of brain tissues obtained from patients with autism, determination of the profile of cytokines and chemokines and characterization of immune mediated reactions in cortical and subcortical regions of autistic brains. Further understanding of the role of neuroglia and immune reactions in the neurobiology of autism may contribute to the design of therapeutic interventions that minimize the neurological and behavioral abnormalities that occur in this disease.
