Microglial activation correlates with severity in Huntington disease: a clinical and PET study

Background: Huntington disease ( HD) is characterized by the progressive death of medium spiny dopamine receptor bearing striatal GABAergic neurons. In addition, microglial activation in the areas of neuronal loss has recently been described in postmortem studies. Activated microglia are known to release neurotoxic cytokines, and these may contribute to the pathologic process. Methods: To evaluate in vivo the involvement of microglia activation in HD, the authors studied patients at different stages of the disease using [ C-11]( R)-PK11195 PET, a marker of microglia activation, and [ C-11] raclopride PET, a marker of dopamine D2 receptor binding and hence striatal GABAergic cell function. Results: In HD patients, a significant increase in striatal [ C-11]( R)-PK11195 binding was observed, which significantly correlated with disease severity as reflected by the striatal reduction in [ C-11] raclopride binding, the Unified Huntington's Disease Rating Scale score, and the patients' CAG index. Also detected were significant increases in microglia activation in cortical regions including prefrontal cortex and anterior cingulate. Conclusions: These [ C-11]( R)-PK11195 PET findings show that the level of microglial activation correlates with Huntington disease ( HD) severity. They lend support to the view that microglia contribute to the ongoing neuronal degeneration in HD and indicate that [ C-11]( R)-PK11195 PET provides a valuable marker when monitoring the efficacy of putative neuroprotecting agents in this relentlessly progressive genetic disorder.

From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition

Growing evidence points toward a critical role for early (prenatal) atypical neurodevelopmental processes in the aetiology of autism spectrum condition (ASC). One such process that could impact early neural development is inflammation. We review the evidence for atypical expression of molecular markers in the amniotic fluid, serum, cerebrospinal fluid (CSF), and the brain parenchyma that suggest a role for inflammation in the emergence of ASC. This is complemented with a number of neuroimaging and neuropathological studies describing microglial activation. Implications for treatment are discussed.