Search Results (5)

Background/Objectives: Major Depression (MD) is a common disorder that has significant social and economic impacts. Approximately 30% of all MD patients are refractory to common treatments, representing a major obstacle to managing the impacts of depression. One potential explanation for the incomplete treatment efficacy in MD is a substantial divergence in the mechanisms and brain networks involved in different subtypes of the disorder. The aim of this study was to identify novel brain regional targets for MD clinical screening using a gene-informed approach. Methods: A new analysis pipeline, called “Analysis Tool for Local Association of Neuronal Transcript Expression” (ATLANTE), was generated and validated. The pipeline identifies brain regions based on the shared high expression of user-generated gene lists; in this study, the pipeline was applied to discover brain regions that may be significant to MD. Results: Nine discrete brain regions of interest to MD were identified, including the temporal pole, anterior transverse temporal gyrus (Heschl’s gyrus), olfactory tubercle, ventral tegmental area, postcentral gyrus, CA1 of the hippocampus, olfactory area, perirhinal gyrus, and posterior insular cortex. The application of network and clustering analyses identified genes of special importance, including, most notably, PRKN. Conclusions: This study provides two major insights. The first is that several brain regions have unique MD-associated genetic architectures, indicating a potential explanation for subtype-specific dysfunction. The second insight is that the PRKN gene, which is strongly associated with Parkinson’s disease, is a key player amongst the MD-associated genes. These findings reveal novel targets for the clinical screening of depression and reinforce a mechanistic connection between MD and Parkinson’s disease. Full article

Phortica okadai, a vector of Thelazia callipaeda, is associated with an increasing incidence of thelaziasis. The complex habitat and chemosensory system of P. okadai are critical for its proliferation and expansion. However, ultrastructural data across developmental stages remain limited. This study used scanning electron microscopy to examine the ultrastructure of P. okadai developmental stages, with a focus on head sensilla. The results showed that the eggs of P. okadai are dark brown and cylindro-oval. The larvae are vermiform, divided into 11 segments. The pupae are marked by a conspicuous respiratory tubercle, and the posterior spiracle contains three distinct spiracular slits. Among five types of sensilla (trichoid, intermediate, chaetica, coeloconic, and basiconic), coeloconic, intermediate, and trichoid sensilla were predominantly found on the antennae, while basiconic and chaetica sensilla were distributed on both the antennae and the maxillary palps of P. okadai. The analysis revealed that the absence of dorsal appendages on the eggs distinguishes P. okadai from D. melanogaster. Males have longer antennae and exhibit sexual dimorphism in the length of sensilla (ChII, TB, and LB). This study provides the first comprehensive ultrastructural characterization of P. okadai developmental stages and head sensilla, laying a foundation for species identification and olfactory system research. Full article

The anterior insula and rolandic operculum are key regions for flavour perception in the human brain; however, it is unclear how taste and congruent retronasal smell are perceived as flavours. The multisensory integration required for sour flavour perception has rarely been studied; therefore, we investigated the brain responses to taste and smell in the sour flavour-processing network in 35 young healthy adults. We aimed to characterise the brain response to three stimulations applied in the oral cavity—sour taste, retronasal smell of mango, and combined flavour of both—using functional magnetic resonance imaging. Effective connectivity of the flavour-processing network and modulatory effect from taste and smell were analysed. Flavour stimulation activated middle insula and olfactory tubercle (primary taste and olfactory cortices, respectively); anterior insula and rolandic operculum, which are associated with multisensory integration; and ventrolateral prefrontal cortex, a secondary cortex for flavour perception. Dynamic causal modelling demonstrated that neural taste and smell signals were integrated at anterior insula and rolandic operculum. These findings elucidated how neural signals triggered by sour taste and smell presented in liquid form interact in the brain, which may underpin the neurobiology of food appreciation. Our study thus demonstrated the integration and synergy of taste and smell. Full article

Mammalian transglutaminases (TGs) catalyze calcium-dependent irreversible posttranslational modifications of proteins and their enzymatic activities contribute to the pathogenesis of several human neurodegenerative diseases. Although different transglutaminases are found in many different tissues, the TG6 isoform is mostly expressed in the CNS. The present study was embarked on/undertaken to investigate expression, distribution and activity of transglutaminases in Huntington disease transgenic rodent models, with a focus on analyzing the involvement of TG6 in the age- and genotype-specific pathological features relating to disease progression in HD transgenic mice and a tgHD transgenic rat model using biochemical, histological and functional assays. Our results demonstrate the physical interaction between TG6 and (mutant) huntingtin by co-immunoprecipitation analysis and the contribution of its enzymatic activity for the total aggregate load in SH-SY5Y cells. In addition, we identify that TG6 expression and activity are especially abundant in the olfactory tubercle and piriform cortex, the regions displaying the highest amount of mHTT aggregates in transgenic rodent models of HD. Furthermore, mHTT aggregates were colocalized within TG6-positive cells. These findings point towards a role of TG6 in disease pathogenesis via mHTT aggregate formation. Full article

Rhes is one of the most interesting genes regulated by thyroid hormones that, through the inhibition of the striatal cAMP/PKA pathway, acts as a modulator of dopamine neurotransmission. Rhes mRNA is expressed at high levels in the dorsal striatum, with a medial-to-lateral expression gradient reflecting that of both dopamine D₂ and adenosine A_2A receptors. Rhes transcript is also present in the hippocampus, cerebral cortex, olfactory tubercle and bulb, substantia nigra pars compacta (SNc) and ventral tegmental area of the rodent brain. In line with Rhes-dependent regulation of dopaminergic transmission, data showed that lack of Rhes enhanced cocaine- and amphetamine-induced motor stimulation in mice. Previous studies showed that pharmacological depletion of dopamine significantly reduces Rhes mRNA levels in rodents, non-human primates and Parkinson’s disease (PD) patients, suggesting a link between dopaminergic innervation and physiological Rhes mRNA expression. Rhes protein binds to and activates striatal mTORC1, and modulates L-DOPA-induced dyskinesia in PD rodent models. Finally, Rhes is involved in the survival of mouse midbrain dopaminergic neurons of SNc, thus pointing towards a Rhes-dependent modulation of autophagy and mitophagy processes, and encouraging further investigations about mechanisms underlying dysfunctions of the nigrostriatal system. Full article