Gene Expression Signatures of Immaturity, Decreased pH, and Neural Hyperexcitation in the Hippocampus of Alzheimer's Disease Model Mice

Neuropsychopharmacology Reports, Год журнала: 2025, Номер 45(1)

Опубликована: Фев. 5, 2025

ABSTRACT Aims Alzheimer's disease (AD) is a leading cause of dementia, with increasing prevalence. Mutations in genes like MAPT, PSEN1, and PSEN2 are risk factors, to the development several AD model mice. Recent hypotheses suggest brain pathology involves abnormal neurodevelopment, decreased pH, neural hyperexcitation. However, it remains unclear what extent these pathologies reflected gene expression changes models. This study aims compare patterns brains multiple mice those related three evaluating overlap. Methods We conducted comprehensive search public databases, collecting 20 datasets from hippocampus These were compared sets hippocampal maturation, hyperexcitation statistically assess Pathway enrichment analysis explored biological relevance changes. Results The overlap maturity‐, pH‐, hyperexcitation‐associated varied across models, showing significant correlations between lower maturity, increased In MAPT mutant APP+PSEN1 homozygous transgenic mice, signatures became more pronounced age. meta‐analysis revealed that associated models involved synaptic channel functions, as well inflammatory responses, consistent previous studies. Conclusion findings pathophysiological play varying roles individual Our recent found negative correlation progression actual pH levels human patients. Considering results presented this study, maturity hyperexcitation, which correlated may also be linked progression. Thus, factors could useful markers for assessing

Язык: Английский

Exploring Oxidative Stress in Disease and Its Connection with Adenosine

Oxygen, Год журнала: 2024, Номер 4(3), С. 325 - 337

Опубликована: Авг. 19, 2024

Oxidative stress, characterized by an imbalance between the production of reactive oxygen species and body’s antioxidant defenses, plays important role in pathogenesis various health conditions, including cancer neurological disorders. For example, excessive ROS can lead to mutations, genomic instability, uncontrolled cell proliferation cancer. In disorders, oxidative stress contributes neuronal damage, inflammation, progression diseases such as Alzheimer’s Parkinson’s diseases. Adenosine, a nucleoside involved energy transfer signal transduction, is crucial maintaining cellular homeostasis. Its extends modulating stress. Adenosine receptors are implicated physiological processes pathophysiology The interplay adenosine signaling complex critical. modulate responses, providing therapeutic potential for conditions where key player. Understanding this connection opens up avenues novel strategies targeting mitigate damage.

Язык: Английский

Upregulation of adenosine A2A receptor by astrocytes is sufficient to trigger hippocampal multicellular dysfunctions and memory deficits.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 26, 2024

Adenosine is an ubiquitous neuromodulator that ensures cerebral homeostasis. It exerts numerous functions through the activation of G-protein-coupled adenosine receptors (ARs), in particular A₁ (A₁R) and A_2A (A_2AR) receptors. Interestingly, A_2AR levels are upregulated cortical hippocampal regions several pathological conditions such as Alzheimer’s disease, tauopathies or epilepsia. Such abnormal upregulations have been particularly reported astrocytes, glial cells play a key role regulating synaptic plasticity. However, overall impact underlying mechanisms associated with increased astrocytes remain poorly understood. In present study, we induced upregulation using dedicated AAVs comprehensively evaluated functional consequences 4 months-old C57Bl6/J mice. Our results show promotes cell-autonomous alterations astrocyte reactivity, morphology transcriptome, link to aging-like phenotype well non-cell autonomous impairments neuronal excitability microglial phenotype. These changes driven by restricted were sufficient induce short-term spatial memory (Y-Maze task) learning (Barnes Maze task). This study highlights astrocytic upregulation, seen various neurological conditions, on development detrimental multicellular response provides additional proof-of-concept for value targeting this receptor different neurodegenerative conditions.

Язык: Английский