These results indicate that the abdominal vagus nerve is necessary for acquiring preference and that the lateral hypothalamus and limbic system could be key areas for integrating the information on gut glutamate and oronasal stimuli. “
“Amyotrophic lateral sclerosis PR 171 is a degenerative disease affecting the motor neurons. In spite of our growing insights into its biology, it remains a lethal condition. The identification of the cause of several of the familial forms of ALS allowed generation of models to study this disease both in vitro and in vivo. Here, we summarize what is known about the pathogenic
mechanisms of ALS induced by hereditary mutations, and attempt to identify the relevance of these findings for understanding the pathogenic mechanisms of the sporadic form of this disease. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with enormous impact on
the quality of life of patients and their carers. Although its incidence is only 1–2 per 100 000, ALS is not rare: the life time risk of developing ALS is estimated to approach 1/400–1/700 (Johnston et al., 2006). Men are somewhat more frequently affected than women (male to female ratio Bortezomib mouse is ∼1.5). Onset usually is in the sixth to seventh decade of life. ALS mainly but not exclusively affects the lower motor neurons in the brainstem and ventral horn of the spinal cord (hence the name amyotrophic) and the upper motor neurons in the cortex that give rise to the corticospinal tract which descends through the lateral spinal cord (hence the name lateral sclerosis). This results in muscle
atrophy and weakness, 17-DMAG (Alvespimycin) HCl fasciculations, and spasticity (Rowland & Shneider, 2001). Although evidence of both upper and lower motor neuron involvement needs to be present to make the diagnosis, lower motor neuron involvement predominates at presentation in some patients, while upper motor neuron involvement can be most prominent in others. The spinal region (limb onset) is affected first in most patients while, in about one out of four or five, the onset is bulbar. ALS is a progressive disease and, although survival is variable, it is fatal in most patients after 3–5 years of evolution, most often due to bulbar dysfunction and respiratory insufficiency. Biologically, ALS is more than a motor neuron disorder. It affects many other neuronal systems, but mostly to a degree below clinical detection threshold. The neuronal circuitries in the frontal region are, however, prominently affected. Many patients have (sometimes subclinical) evidence of frontal dysfunction and ∼15% develop a frontal dementia (Phukan et al., 2007). ALS is familial in ∼10% of patients. It is usually inherited in an autosomal dominant way, but recessive and even X-linked forms exist (Valdmanis et al., 2009; Van Damme & Robberecht, 2009).