ABSTRACT
As a crucial component of the cerebral cholinergic system and the Papez circuit in the basal forebrain, dysfunction of the nucleus basalis of Meynert (NBM) is associated with various neurodegenerative disorders. However, no drugs, including existing cholinesterase inhibitors, have been shown to reverse this dysfunction. Due to advancements in neuromodulation technology, researchers are exploring the use of deep brain stimulation (DBS) therapy targeting the NBM (NBM-DBS) to treat mental and neurological disorders as well as the related mechanisms. Herein, we provided an update on the research progress on cognition-related neural network oscillations and complex anatomical and projective relationships between the NBM and other cognitive structures and circuits. Furthermore, we reviewed previous animal studies of NBM lesions, NBM-DBS models, and clinical case studies to summarize the important functions of the NBM in neuromodulation. In addition to elucidating the mechanism of the NBM neural network, future research should focus on to other types of neurons in the NBM, despite the fact that cholinergic neurons are still the key target for cell type-specific activation by DBS.
ABSTRACT
Mitochondria are the centrol hub for cellular energy metabolisms. They regulate fuel metabolism by oxygen levels, participate in physiological signaling pathways, and act as oxygen sensors. Once oxygen deprived, the fuel utilizations can be switched from mitochondrial oxidative phosphorylation to glycolysis for ATP production. Notably, mitochondria can also adapt to hypoxia by making various functional and phenotypes changes to meet the demanding of oxygen levels. Hypoxic pulmonary hypertension is a life-threatening disease, but its exact pathgenesis mechanism is still unclear and there is no effective treatment available until now. Ample of evidence indicated that mitochondria play key factor in the development of hypoxic pulmonary hypertension. By hypoxia-inducible factors, multiple cells sense and transmit hypoxia signals, which then control the expression of various metabolic genes. This activation of hypoxia-inducible factors considered associations with crosstalk between hypoxia and altered mitochondrial metabolism, which plays an important role in the development of hypoxic pulmonary hypertension. Here, we review the molecular mechanisms of how hypoxia affects mitochondrial function, including mitochondrial biosynthesis, reactive oxygen homeostasis, and mitochondrial dynamics, to explore the potential of improving mitochondrial function as a strategy for treating hypoxic pulmonary hypertension.
ABSTRACT
Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases associated with the degradation of memory and cognitive ability. Current pharmacotherapies show little therapeutic effect in AD treatment and still cannot prevent the pathological progression of AD. Deep brain stimulation (DBS) has shown to enhance memory in morbid obese, epilepsy and traumatic brain injury patients, and cognition in Parkinson's disease (PD) patients deteriorates during DBS off. Some relevant animal studies and clinical trials have been carried out to discuss the DBS treatment for AD. Reviewing the fornix trials, no unified conclusion has been reached about the clinical benefits of DBS in AD, and the dementia ratings scale has not been effectively improved in the long term. However, some patients have presented promising results, such as improved glucose metabolism, increased connectivity in cognition-related brain regions and even elevated cognitive function rating scale scores. The fornix plays an important regulatory role in memory, attention, and emotion through its complex fibre projection to cognition-related structures, making it a promising target for DBS for AD treatment. Moreover, the current stereotaxic technique and various evaluation methods have provided references for the operator to select accurate stimulation points. Related adverse events and relatively higher costs in DBS have been emphasized. In this article, we summarize and update the research progression on fornix DBS in AD and seek to provide a reliable reference for subsequent experimental studies on DBS treatment of AD.
