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Kunming, November 4 (Reporter Hu Yuanhang) The Kunming Institute of Zoology, Chinese Academy of Sciences, released news on the 3rd that the research team of Li Jiali of the Institute used a mouse disease model to analyze the neural circuit mechanism
of the occurrence of irritable symptoms of Alzheimer's disease.
The relevant research results were recently published in
the international academic journal Cell Reports.
Alzheimer's disease (AD) is one of the most important neurodegenerative diseases with complex etiology and pathogenesis affecting the health of the elderly population, with progressive cognitive decline as the most significant clinical manifestation, and the main neuropathological changes are the deposition of amyloid plaques and nerve fiber tangles
in the brain 。 Clinically, in addition to cognitive dysfunction, patients are often accompanied by neuropsychiatric symptoms such as depression and anxiety, increased aggressive behavior, abnormal rhythms, and auditory hallucinations, which not only seriously affect the quality of life of patients and caregivers, but also may accelerate the cognitive decline of patients
.
However, the neural circuit mechanism for the onset and progression of such symptoms is currently unknown
.
The medial prefrontal cortex (mPFC) plays an important role
in the progression of AD lesions.
Studies have found that pyramidal tract (PT) neurons projected to the thalamus, superior thalamus and brainstem and other extracranial regions have an important regulatory role
in non-cognitive functions such as feeding, attack, sleep, and emotions.
Therefore, it is likely that PT neurons in the mPFC region of AD lesions mediate the occurrence
of neuropsychiatric symptoms in patients.
In addition, PT neurons can be divided into A-type and B-type according to projection and expression characteristics
.
It is not clear whether these two types of neurons have different pathological changes in AD lesions and whether they play different roles
in the occurrence of neuropsychiatric symptoms.
In view of the above scientific problems, researchers in Li Jiali's research group successfully analyzed the specific electrophysiological abnormalities of two types of PT neurons in diseases and their relationship
with aggressive behavior by using the AD mouse model as the research object.
The researchers used the reverse tracer virus to label two types of PT neurons of PFC, so as to record them separately whole-cell, and found that the intrinsic excitatory abnormalities of the two types of neurons in AD mouse models showed high differences
.
In model mice, A-type PT neurons projected to the thalamus showed increased intrinsic excitability and increased action potential emission; However, B-type PT neurons that are mainly projected to the brainstem show a decrease in the capacity of action potential acceptance and a decrease
in action potential emission.
Among them, the increase of excitability of A-type PT neurons led to an increase in the aggressive behavior of model mice, and the excitability of such neurons could be regulated bidirectionally by chemical genetic means
.
In addition, by comparing the differences in transcriptomics between the two types of neurons, the mechanism of electrophysiological abnormalities of A-type PT neurons was located in the voltage-gated potassium channel Kv6.
3, and the decrease in the expression of Kv6.
3 of such neurons was determined by immunofluorescence, western blotting, single-cell qPCR and other means, and the electrophysiological abnormalities and the increase
of aggressive behavior of A-type PT neurons in model mice were reversed through the overexpression of Kv6.
3.
This study provides new insights into the mechanism of the occurrence of neuropsychiatric symptoms of AD, and also provides a new basis
for the classification of PFC neurons.
(End)