The streptozotocin (STZ) experimental model of sporadic Alzheimer’s disease (SAD), the most prevalent form of this type of dementia, has become a valuable tool to study the behavioral and morphological changes that occur during the gradual development of this pathology. We used the STZ experimental model in combination with the novel object recognition test (NORT) and immunohistochemical techniques to evaluate the recognition memory decline and morphological alterations in memory-related structures (hippocampus and cortex). Our analysis included five different time points after intracerebroventricular (ICV) administration of 3 mg/kg of STZ or artificial cerebrospinal fluid (aCSF) as a control. The time points included three distinct stages: early (15 and 30 days), intermediate (60 days), and late (90 and 120 days). We found that recognition memory impairment started in the intermediate stage and persisted through the later stages. Morphologically, we detected significant astrogliosis starting in the early stages, whereas cholinergic changes began in the intermediate stage. No neuronal loss was observed at any of the time points analyzed. Our results further support the hypothesis that astrogliosis constitutes an initial pathological event that may compromise the hippocampal cholinergic system and can contribute to the onset of recognition memory deficits.

CCDC28B (coiled-coil domain-containing protein 28B) was identified as a modifier in the ciliopathy Bardet-Biedl syndrome (BBS). Our previous work in cells and zebrafish showed that CCDC28B plays a role regulating cilia length in a mechanism that is not completely understood. Here we report the generation of aCcdc28bmutant mouse using CRISPR/Cas9 (Ccdc28b mut). Depletion of CCDC28B resulted in a mild phenotype.Ccdc28b mutanimalsi)do not present clear structural cilia affectation, although we did observe mild defects in cilia density and cilia length in some tissues,ii)reproduce normally, andiii)do not develop retinal degeneration or obesity, two hallmark features of reported BBS murine models. In contrast,Ccdc28b mutmice did show clear social interaction defects as well as stereotypical behaviors. This finding is indeed relevant regardingCCDC28Bas a modifier of BBS since behavioral phenotypes have been documented in BBS. Overall, this work reports a novel mouse model that will be key to continue evaluating genetic interactions in BBS, deciphering the contribution ofCCDC28Bto modulate the presentation of BBS phenotypes. In addition, our data underscores a novel link betweenCCDC28Band behavioral defects, providing a novel opportunity to further our understanding of the genetic, cellular, and molecular basis of these complex phenotypes.

Current understanding recognizes that ribosomal proteins (RPs) have regulatory roles beyond their canonical structural functions in translation, raising the question of how their expression is organized across cell types. Given the diversity of neuronal cell types, understanding RP gene expression at the neuronal subtype level is an important and previously inaccessible question. Here, leveraging advances in single-cell transcriptomics, we analyzed single-cell RNA-seq datasets from the mouse cerebral cortex and hippocampus to examine RP mRNA expression across neuronal subtypes. We observed distinct RP mRNA expression profiles between excitatory and inhibitory neurons and found that higher Rps27 transcript levels in inhibitory neurons corresponded to increased Rps27 protein abundance. Beyond excitatory-inhibitory differences, RP mRNA expression further segregated across well-defined neuronal subclasses, with 59 of 84 RP genes differentially expressed, including enrichment of Rpl21 in Lamp5 and Rps27 in Vip interneurons. These patterns were consistent across cortical regions and reproducible across two independent single-cell technologies (Smart-seq2 and 10x Genomics). Analysis of aging- and stress-associated datasets revealed stable RP expression signatures, with limited phenotype-linked changes. Together, we present a comprehensive atlas of ribosomal protein gene expression at neuronal subclass resolution, revealing robust subclass-specific transcriptional signatures suggesting an underestimated regulatory layer.