Implications for microglial sex differences in tau-related neurodegenerative diseases

Microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice

“…It has been recently recognized that microglia possess sexually dimorphic roles in the developing, adult and aged brain that have been associated with neurological disorders such as autism and traumatic brain injuries. 35,[58][59][60][61] The adult female mice, under physiological conditions, are usually exposed to short-term changes in gonadal hormones levels (estrous cycle). A recent study demonstrates that neuronal chromatin organization in the female ventral hippocampus of mouse fluctuates with the estrous cycle and that chromatin organizational changes associate with the transcriptional activity of genes important for neuronal function and behaviour.…”

Trajectories of Persistent Postconcussion Symptoms and Factors Associated With Symptom Reporting After Mild Traumatic Brain Injury

“…46 Interestingly, and perhaps relevant for headache observed after MTBI, is that signaling mechanisms underlying pain hypersensitivity (eg, glial cell activation) are sexually dimorphic. 47,48 Further adding to the complexity, not only gender but also perceptions of gender inequality are associated www.archives-pmr.org with psychological distress. 49 Future studies should further target how sex and gender influence outcome after MTBI.…”

Sex and Gender Differences in Neurodegenerative Diseases: Challenges for Therapeutic Opportunities

“…Even if microglia in the adult male brain appear to be more reactive to inflammatory events compared to females, inflammatory events in adulthood appear to promote age-related microglial dysfunction in females. However, microglia shift to a more pro-inflammatory state with reduced homeostatic functions during aging in both sexes [ 7 ]. Sexually dimorphic immune responses could also arise due to incomplete inactivation of the X chromosome in females.…”

“…In 33 pediatric and adult SMA patients, an inflammatory cytokine signature was found in both serum and CSF as an index of inflammation and immune system activation at peripheral and central levels [ 102 ]. Furthermore, peripheral immune organ abnormalities and T-cell maturation dysfunction have emerged in mouse models of SMA, and it is reasonable to assume that these intrinsic T-cell alterations may result in an abnormal neuroinflammatory response and disease exacerbation [ 7 ]. Increased astrogliosis was observed in necropsies of patients [ 103 ] and also in the mouse model with selective deletion of exon 7 in the SMN gene (SmnΔ7) both at pre-symptomatic and symptomatic stages [ 104 ], whereas microglial activation was only seen in the SmnΔ7 mouse model but not in the more severe mice with the homozygous Smn knockout allele (Smn −/−; SMN2) ( Table 1 ) [ 105 , 106 ].…”

“…Of interest, most of the clinical differences reported in NDs seem to be closely linked to sex, which may be justified by female/male significant changes in autoimmune mechanisms. It is worthy to note that microglia showed sexually dimorphic roles in the developing brain, which might explain some sex-differences in NDs [ 7 ].…”