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Glial cells play a pivotal role in the inflammatory processes, which are common features of several neurodevelopmental and neurodegenerative disorders. Their major role in modulating neuroinflammation underscores their significance in these conditions. Engrailed‐2 knockout mice (En2−/−) are considered a valuable model for autism spectrum disorder (ASD) due to their distinctive neuroanatomical and behavioral traits. Given the higher prevalence of ASD in males, our objective was to investigate glial and interneuron alterations in the cerebellum of En2−/− mice compared with wild‐type (WT) mice in both sexes. We employed immunohistochemical analysis to assess cell density for all cell types studied and analyzed the area (A) and shape factor (SF) of microglia cell bodies. Our findings revealed the following: (a) In WT mice, the density of microglia and astrocytes was higher in females than in males, while interneuron density was lower in females. Notably, in En2‐mutant mice, these differences between males and females were not present. (b) In both male and female En2−/− mice, astrocyte density exceeded that in WT mice, with microglia density being greater only in females. (c) In WT females, microglia cell bodies exhibited a larger area and a lower shape factor compared to WT males. Remarkably, the En2 mutation did not appear to influence these sex‐related differences. (d) In both male and female En2−/− mice, we observed a consistent pattern: microglia cell bodies displayed a larger area and a smaller shape factor. Given the ongoing debate surrounding the roles of glia and sex‐related factors in ASD, our observations provide valuable insights into understanding how an ASD‐associated gene En2 affects specific cell types in the cerebellum. [ABSTRACT FROM AUTHOR]

Neurotoxins such as rotenone, 1-methyl-4-phenylpyridinium (MPP+) and 6-hydroxydopamine (6-OHDA) are well known for their high toxicity on dopaminergic neurons and are associated with Parkinson's disease (PD) in murine models and humans. In addition, PD patients often have glucose intolerance and may develop type 2 diabetes (T2D), whereas T2D patients have higher risk of PD compared to general population. Based on these premises, we evaluated the toxicity of these three toxins on pancreatic β-cell lines (INS-1 832/13 and MIN6) and we showed that rotenone is the most potent for reducing β-cells viability and altering mitochondrial structure and bioenergetics in the low nanomolar range, similar to that found in dopaminergic cell lines. MPP+ and 6-OHDA show similar effects but at higher concentration. Importantly, rotenone-induced toxicity was counteracted by α-tocopherol and partially by metformin, which are endowed with strong antioxidative and cytoprotective properties. These data show similarities between dopaminergic neurons and β-cells in terms of vulnerability to toxins and pharmacological agents capable to protect both cell types. [ABSTRACT FROM AUTHOR]

Bipolar disorders (BDs) are a heterogeneous group of severe affective disorders generally described by the alternation of (hypo)manic, depressive, and mixed phases, with euthymic intervals of variable duration. BDs are burdened with high psychiatric and physical comorbidity, increased suicide risk and reduced life expectancy. In addition, BDs can progress into complicated forms (e.g., mixed states, rapid/irregular cycling), which are more difficult to treat and often require personalized pharmacological combinations. Mood stabilizers, particularly Lithium and Valproic acid (VPA), still represent the cornerstones of both acute and chronic pharmacotherapies of BDs. Lithium is the gold standard in BD-I and BDII with typical features, while VPA seems more effective for atypical forms (e.g., mixed-prevalence and rapid-cycling). However, despite appropriate mood stabilization, many patients show residual symptoms, and more than a half recur within 1-2 years, highlighting the need of additional strategies. Among these, the association of atypical antipsychotics (AAPs) with mood stabilizers is recurrent in the treatment of acute phases, but it is also being growingly explored in the maintenance pharmacotherapy. These combinations are clinically more aggressive and often needed in the acute phases, whereas simplifying pharmacotherapies to mood stabilizers only is preferable in the long-term, whenever possible. When mood stabilizers are not enough for maintenance treatment, Quetiapine and, less consistently, Aripiprazole have been proposed as the most advisable adjunctive strategies, for their safety and tolerability profiles. However, in view of the increased risk of serious adverse effects, a careful patient-centered balance between costs and benefits is mandatory., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)