A spontaneous mutation in the lysosomal acid phosphatase (Acp2) enzyme (nax: naked–ataxia) in experimental mice results in delayed hair appearance and severe cytoarchitectural impairments of the cerebellum, such as a Purkinje cell (PC) migration defect. In our previous investigation, our team showed that Acp2 expression plans a significant role in cerebellar development. On the other hand, the dopaminergic system is also a player in central nervous system (CNS) development, including cerebellar structure and function. In the current investigation, we have explored how Acp2 can be involved in the regulation of the dopaminergic pathway in the cerebellum via the regulation of dopamine receptor expression and patterning. We provided evidence about the distribution of different dopamine receptors in the developing cerebellum by comparing the expression of dopamine receptors on postnatal days (P) 5 and 17 between nax mice and wild–type (wt) littermates. To this aim, immunohistochemistry and Western blot analysis were conducted using five antibodies against dopamine receptors (DRD1, –2, –3, –4, and –5) accompanied by RNAseq data. Our results revealed that DRD1, –3, and –4 gene expressions significantly increased in nax cerebella but not in wt, while gene expressions of all 5 receptors were evident in PCs of both wt and nax cerebella. DRD3 was strongly expressed in the PCs’ somata and cerebellar nuclei neurons at P17 in nax mice, which was comparable to the expression levels in the cerebella of wt littermates. In addition, DRD3 was expressed in scattered cells in a granular layer reminiscent of Golgi cells and was observed in the wt cerebella but not in nax mice. DRD4 was expressed in a subset of PCs and appeared to align with the unique parasagittal stripes pattern. This study contributes to our understanding of alterations in the expression pattern of DRDs in the cerebellum of nax mice in comparison to their wt littermates, and it highlights the role of Acp2 in regulating the dopaminergic system.

Alzheimer's disease (AD) is the most common cause of dementia in adulthood, which is followed by cognitive impairment and behavioral deficits. Today, mesenchymal stem cell (MSC)-based therapy is a good therapeutic option to improve regenerative medicine in neurodegenerative disorders including AD. The aim of this study is to investigate the effects of the human Wharton’s jelly-derived MSCs (WJ-MSCs) on Alzheimer's rat models by studying the expression of neurotrophic factors involved in neurodegenerative diseases such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), as well as expression of apoptotic factors such as B-cell lymphoma 2 (BCL2, apoptosis inhibitor), BCL2-associated X protein (BAX, apoptosis initiator), and Caspase 3 (apoptosis executioner). Rat AD modeling was performed by intrahippocampal injection of amyloid β 1–42 (Aβ 1–42, 8 µg/kg). Animals were divided into 3 groups of 8 rat: I) control II) AD model III) MSC-treated. Behavioral tests (i.e. Passive Avoidance and Morris Water Maze) showed cognitive improvement, and amelioration of cells in the CA1 area of the hippocampus has been detected by cresyl violet (nissl) staining. Also, real-time polymerase chain reaction (RT-PCR) of the hippocampus indicated an increase in BDNF and NGF genes and a decrease in apoptosis-related genes (BCL2, BAX, and Caspase 3). Overall, WJ-MSCs improved cognitive functions in AD rat models by increasing neurotrophic factors and decreasing apoptotic factors.