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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]

The reticular thalamic nucleus (Rt) is a sheet of neurons that surrounds the dorsal thalamus laterally, along its dorso‐ventral and rostro‐caudal axes. It consists of inhibitory neurons releasing gamma‐aminobutyric acid (GABA). This nucleus participates in the circuitry between the thalamus and the cerebral cortex, and its impairment is associated with neuro‐psychiatric disorders. In this study, we investigated the Rt anatomy of Engrailed‐2 knockout mice (En2−/−), a mouse model of autism spectrum disorder (ASD), using parvalbumin as an immunohistochemical marker. We compared 4‐ and 6‐week‐old wild type (WT) and En2−/− mice using various morphometric parameters: cell area, shape factor, circularity and cell density. Significant differences were present in 6‐week‐old male mice with different genetic background (WT vs. En2−/−): the Rt neurons of En2−/− mice showed a bigger cell area, shape factor and circularity when compared with WT. Age (4 weeks vs. 6 weeks) influenced the shape factor of WT females, the circularity and cell density of En2−/− males, and the shape factor and circularity of En2−/− females. Gender affected cell density in 4‐week‐old WT mice, shape factor and cellularity of 6‐week‐old WT mice, and cell area, shape factor and cell density of En2−/− at 6 weeks. Intrasubject (left–right) asymmetry of Rt was never observed. These results show for the first time that sex‐ and age‐related changes occur in the Rt GABAergic neurons of the En2−/− ASD mouse model. [ABSTRACT FROM AUTHOR]

• Artificial light is an environmental factor influencing human health and chronic exposure can exert negative effects. • Light can penetrate in human brain and other tissues in the red and near infrared range. • Light can damage biological tissues by photoactivation of endogenous compounds with the formation of free radicals. • Prolonged exposure of rodents to bright light exerts detrimental effects on dopamine neurons in the substantia nigra. • Specific wavelengths locally applied to the substantia nigra exert protective effects on dopamine neurons in models of PD. Light exerts a major influence on human behaviour and health, mainly owing to the importance of sight in our lives, but also due to its entrainment of daily rhythms via the suprachiasmatic nucleus, the master pacemaker. Light may also be a useful clinical medium, as in lumino-therapy for the improvement of depressed mood. Further, as discussed herein, local application of near infrared light to the substantia nigra exerts neuroprotective properties in models of Parkinson's disease. However, light also has a darker side. In general, as regards the growing problem to human health - and the natural world - of excess exposure to artificial light: both urban glow and ubiquitous screens. Moreover, over-exposure to light, in particular fluorescent light, disrupts circadian rhythms and sleep, and may damage dopaminergic neurons. Is it, then, a neglected risk factor for Parkinson's disease? The present article discusses epidemiological and experimental evidence supporting beneficial and potentially deleterious impact of light on dopaminergic neurons and highlights the mechanisms whereby light might influence neuronal tissue. [ABSTRACT FROM AUTHOR]

Tissue clarification has been recently proposed to allow deep tissue imaging without light scattering. The clarification parameters are somewhat arbitrary and dependent on tissue type, source and dimension: every laboratory has its own protocol, but a quantitative approach to determine the optimum clearing time is still lacking. Since the use of transgenic mouse lines that express fluorescent proteins to visualize specific cell populations is widespread, a quantitative approach to determine the optimum clearing time for genetically labeled neurons from thick murine brain slices using CLARITY2 is described. In particular, as the main objective of the delipidation treatment is to clarify tissues, while limiting loss of fluorescent signal, the "goodness" of clarification was evaluated by considering the bulk tissue clarification index (BTCi) and the fraction of the fluorescent marker retained in the slice as easily quantifiable macroscale parameters. Here we describe the approach, illustrating an example of how it can be used to determine the optimum clearing time for 1 mm-thick cerebellar slice from transgenic L7GFP mice, in which Purkinje neurons express the GFP (green fluorescent protein) tag. To validate the method, we evaluated confocal stacks of our samples using standard image processing indices (i.e., the mean pixel intensity of neurons and the contrast-to -noise ratio) as figures of merit for image quality. The results show that detergent-based delipidation for more than 5 days does not increase tissue clarity but the fraction of GFP in the tissue continues to diminish. The optimum clearing time for 1 mm-thick slices was thus identified as 5 days, which is the best compromise between the increase in light penetration depth due to removal of lipids and a decrease in fluorescent signal as a consequence of protein loss: further clearing does not improve tissue transparency, but only leads to more protein removal or degradation. The rigorous quantitative approach described can be generalized to any clarification method to identify the moment when the clearing process should be terminated to avoid useless protein loss. [ABSTRACT FROM AUTHOR]

The present review update the relationship between acetaldehyde (ACE) and parkinsonism with a specific focus on the role of P450 system and CYP 2E1 isozyme particularly. We have indicated that ACE is able to enhance the parkinsonism induced in mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin able to damage the nigrostriatal dopaminergic pathway. Similarly diethyldithiocarbamate, the main metabolite of disulfiram, a drug widely used to control alcoholism, diallylsulfide (DAS) and phenylisothiocyanate also markedly enhance the toxin-related parkinsonism. All these compounds are substrate/inhibitors of CYP450 2E1 isozyme. The presence of CYP 2E1 has been detected in the dopamine (DA) neurons of rodent Substantia Nigra (SN), but a precise function of the enzyme has not been elucidated yet. By treating CYP 2E1 knockout (KO) mice with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the SN induced lesion was significantly reduced when compared with the lesion observed in wild-type animals. Several in vivo and in vitro studies led to the conclusion that CYP 2E1 may enhance the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice by increasing free radical production inside the dopaminergic neurons. ACE is a good substrate for CYP 2E1 enzyme as the other substrate-inhibitors and by this way may facilitate the susceptibility of dopaminergic neurons to toxic events. The literature suggests that ethanol and/or disulfiram may be responsible for toxic parkinsonism in human and it indicates that basal ganglia are the major targets of disulfiram toxicity. A very recent study reports that there are a decreased methylation of the CYP 2E1 gene and increased expression of CYP 2E1 mRNA in Parkinson's disease (PD) patient brains. This study suggests that epigenetic variants of this cytochrome contribute to the susceptibility, thus confirming multiples lines of evidence which indicate a link between environmental toxins and PD. [ABSTRACT FROM AUTHOR]