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The cerebellar cortex has the most obvious neuropathology, yet cells in other brain regions are also abnormal. A-T mouse models have been produced that replicate much, though not all, of the complex A-T phenotype. Nongenetic factors, including modulations of the immune status of the animal, have also recently been found to play a role in the disease phenotype. Here we report that these modulations show both cytokine and brain region specificity. The CNS changes induced by broad-spectrum immune challenges, such as lipopolysaccharide (LPS) injections are a complex mixture of neuroprotective (TNF\u03b1) and neurodegenerative (IL1\u03b2) cytokine responses that change over time. For example, LPS first induces a protective response in A-T neurons through activation of tissue repair genes through infiltration of monocytes with M2 phenotype, followed over time by a set of more degenerative responses. Additional phenotypic complexity arises because the neuronal response to an immune challenge is regionally variable; cerebellum and cortex differ in important ways in their patterns of cellular and biochemical changes. Tracking these changes reveals an important though not exclusive role for the MAP kinase pathway. Our findings suggest brain responses to cytokine challenges are temporally and regionally specific and that both features are altered by the absence of ATM. This implies that management of the immune status of A-T patients might have significant clinical benefit.<\/jats:p>","DOI":"10.1523\/eneuro.0032-15.2015","type":"journal-article","created":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T01:49:28Z","timestamp":1438393768000},"page":"ENEURO.0032-15.2015","source":"Crossref","is-referenced-by-count":11,"title":["Individual Cytokines Modulate the Neurological Symptoms of<i>ATM<\/i>Deficiency in a Region Specific Manner"],"prefix":"10.1523","volume":"2","author":[{"given":"Chin 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