CCL5-glutamate cross-talk in astrocyte-neuron communication in multiple sclerosis

The immune system (IS) and the central nervous system (CNS) are functionally coupled, and a large number of endogenous molecules (i.e., the chemokines for the IS and the classic neurotransmitters for the CNS) are shared in common between the two systems. These interactions are key elements for the elucidation of the pathogenesis of central inflammatory diseases. In recent years, evidence has been provided supporting the role of chemokines as modulators of central neurotransmission. It is the case of the chemokines CCL2 and CXCL12 that control pre- and/or post-synaptically the chemical transmission. This article aims to review the functional cross-talk linking another endogenous pro-inflammatory factor released by glial cells, i.e., the chemokine Regulated upon Activation Normal T-cell Expressed and Secreted (CCL5) and the principal neurotransmitter in CNS (i.e., glutamate) in physiological and pathological conditions. In particular, the review discusses preclinical data concerning the role of CCL5 as a modulator of central glutamatergic transmission in healthy and demyelinating disorders. The CCL5-mediated control of glutamate release at chemical synapses could be relevant either to the onset of psychiatric symptoms that often accompany the development of multiple sclerosis (MS), but also it might indirectly give a rationale for the progression of inflammation and demyelination. The impact of disease-modifying therapies for the cure of MS on the endogenous availability of CCL5 in CNS will be also summarized. We apologize in advance for omission in our coverage of the existing literature

Choreoacanthocytosis in a Mexican family.

BACKGROUND: Choreoacanthocytosis (CHAC) (Online Mendelian Inheritance in Man accession No. 200150) is a hereditary neurodegenerative syndrome characterized by movement disorders, cognitive decline, myopathy, behavioral changes, and acanthocytosis and is caused by mutations in the VPS13A gene. OBJECTIVE: To describe the cases of 2 Mexican women with clinical and molecular characteristics compatible with CHAC. DESIGN: Case reports. Patients Choreoacanthocytosis was identified in 2 Mexican mestizo sisters with healthy consanguineous parents. Clinical manifestations began at different ages. RESULTS: The onset of signs and symptoms of CHAC in the proband was at age 32 years and was characterized by balancing problems followed by chorea, compulsive lip and tongue biting with buccolingual self-mutilation, dysarthria, dysphagia, and weight loss. The first clinical manifestations in the proband's sister occurred at age 45 years and included multiple motor and verbal tics, with coprolalia, followed by lip and tongue biting, self-mutilation, and chorea. The clinical findings in both sisters were remarkable for acanthocytosis that developed late, when neurologic changes were already evident. Mutation screening of the VPS13A gene revealed homozygosity for the frameshift mutation c.3556_3557dupAC in exon 33. Currently, the proband's sister, in whom neurologic defects developed 13 years after onset of CHAC in the proband, is the least affected. CONCLUSIONS: The same mutation of the VPS13A gene can be expressed differently in the same family. This observation confirms the notion that there is considerable heterogeneity in the clinical manifestation of CHAC

Endogenous Neurogenesis After Traumatic Brain Injury

Adult neurogenesis in the central nervous system (CNS) is a distinctive process that leads to the renewal of neuronal populations in brain regions such as the olfactory bulb and hippocampal dentate gyrus. The existence of self-renewing, migratory neural stem/progenitor cells (NSPCs) in the adult brain has led to discoveries about their homeostatic role in neurogenesis and injury-induced changes following CNS trauma. Expansion and ectopic migration of quiescent endogenous NSPCs is thought to stabilize the injured milieu with the potential of providing cellular replacement of damaged or lost neurons. A better understanding of how resident NSPCs are robustly activated as well as limited will provide a way forward for maximizing the potential of these cells to reconstitute the cellular architecture in an attempt to regain function after injury. Here, we will focus specifically on traumatic brain injury and its effects on the neurogenic compartments in the adult brain and the subsequent responses