French Institute of Health and Medical Research

About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.

Apathy and the Functional Anatomy of the Prefrontal Cortex–Basal Ganglia Circuits

Abstract: The clinical signs grouped under the concept of apathy are a common feature of prefrontal and basal ganglia lesions or dysfunctions and can therefore help to improve our understanding of the functional anatomy of the prefrontal-basal ganglia system. Apathy is here defined as a quantitative reduction of voluntary, goal-directed behaviors. The underlying mechanisms responsible for apathy can be divided into three subtypes of disrupted processing: 'emotional-affective', 'cognitive' and 'auto-activation'. Apathy due to the disruption of 'emotional-affective' processing refers to the inability to establish the necessary linkage between emotional-affective signals and the ongoing or forthcoming behavior. It may be related to lesions of the orbital-medial prefrontal cortex or to the related subregions (limbic territory) within the basal ganglia (e.g. ventral striatum, ventral pallidum). Apathy due to the disruption of 'cognitive' processing refers to difficulties in elaborating the plan of actions necessary for the ongoing or forthcoming behavior. It may be related to lesions of the dorsolateral prefrontal cortex and the related subregions (associative territory) within the basal ganglia (e.g. dorsal caudate nucleus). The disruption of 'auto-activation' processing refers to the inability to self-activate thoughts or self-initiate actions contrasting with a relatively spared ability to generate externally driven behavior. It is responsible for the most severe form of apathy and in most cases the lesions affect bilaterally the associative and limbic territories of the internal portion of the globus pallidus. It characterizes the syndrome of 'auto-activation deficit' (also known as 'psychic akinesia' or 'athymormia'). This syndrome implies that direct lesions of the basal ganglia output result in a loss of amplification of the relevant signal, consequently leading to a diminished extraction of this signal within the frontal cortex. Likewise, apathy occurring in Parkinson's disease could be interpreted as secondary to the loss of spatial and temporal focalization of the signals transferred to the frontal cortex. In both situations (direct basal ganglia lesions and nigro-striatal dopaminergic loss), the capacity of the frontal cortex to select, initiate, maintain and shift programs of actions is impaired.

Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration

Abstract: Hypoxia stimulates angiogenesis through the binding of hypoxia-inducible factors to the hypoxia-response element in the vascular endothelial growth factor (Vegf) promotor. Here, we report that deletion of the hypoxia-response element in the Vegf promotor reduced hypoxic Vegf expression in the spinal cord and caused adult-onset progressive motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis. The neurodegeneration seemed to be due to reduced neural vascular perfusion. In addition, Vegf165 promoted survival of motor neurons during hypoxia through binding to Vegf receptor 2 and neuropilin 1. Acute ischemia is known to cause nonselective neuronal death. Our results indicate that chronic vascular insufficiency and, possibly, insufficient Vegf-dependent neuroprotection lead to the select degeneration of motor neurons.