Table 2 Microglia activation in ASD and schizophrenia

Overall deregulation of the immune system with increased production of pro-inflammatory cytokines, possible as a result of the activation of microglia

(Patterson, 2009; Rodriguez and Kern, 2011; Takano, 2015)

(Patterson, 2009; Takahashi et al. 2016)

Upregulation of iNOS, glutaminase, and inducible cyclooxygenase (COX-2) leading to an increase of nitric oxide (NO), glutamate and prostaglandins, respectively. These substances have a toxic effect in neurons(Fernandes et al. 2014)

Decrease in NK cell function, possibly as a result of increased production of NO by microglia

Enstrom et al., 2009)(Warren et al. 1987)

(Karpinski et al. 2016)

NK cells play important functions in innate immunity, sppecially against intracellular infections. Disfunction of NK cells may predispose to adverse neuroimmune interactions, namely, during development.

Glutathione (GSH) depletion, possibly caused by i-NOS increase

(Rodriguez and Kern, 2011)

(Ivanova et al. 2015; Zhang et al. 2016)

GSH (an antioxidant) has a protective effect on neurons. Its decrease may lead to easier neuron damage.

Increase in anti-phospholipid antibodies (APLAs)

Careaga et al., 2013)

NF

Increased risk of blood clotting and pregnancy losses

Denser distribution of microglia

In fronto-insular and visual cortex (Tetreault et al. 2012)

In pre-frontal white matter (Hercher et al. 2014). In frontal and temporal cortex(Garey, 2010)

Reduced number of neurons and/or disrupted neural connectivity

Increased levels of glial fibrillary acidic protein (GFAP) in the brain

Cerebrospinal fluid (Ahlsen et al. 1993). Cerebelum(Bailey et al. 1998). Anterior cingulate cortex white matter(Crawford et al. 2015)

Frontal cortex (Rao et al. 2013)

GFAP is an important protein in the central nervous system, in particular in repair after CNS injury. An increase in GFAP is a hallmark of reactive gliosis (Kamphuis et al., 2015), which follows trauma or injury.

Increases expression of NF-kB in activated microglia

(Young et al. 2011)

(Rao et al. 2013)

NF-kB plays a key role in inflammation, through its ability to induce transcription of pro-inflammatory genes.

Presence of HLA-DR positive cells

In serum(Lee et al. 2006; Mead and Ashwood, 2015)

Brain, post-mortem (Bayer et al. 1999; Garey, 2010; Radewicz et al. 2000; Rao et al. 2013)

HLA-DR is an immunohistochemical marker that is expressed in antigen presenting cells (B lymphocytes, dendritic cells, macrophages). It reacts with activated microglia cells.

Increase in calprotectin

Increased levels in feces(de Magistris et al. 2010)

Localization in microglia(Foster et al. 2006)

Calprotectin is a pro-inflammatory marker. Increased fecal levels are due to increased intestinal permeability.

Activation of microglia found by PET

(Suzuki et al. 2013)

(Bloomfield et al. 2016)

Confirms the importance of neuroinflammation in ASD and schizophrenia revealed by studies based on the analysis of tissues