Astrocytes Mediate Cholinergic Regulation of Adult Hippocampal Neurogenesis and Memory Through M1 Muscarinic Receptor

Li, Weipeng; Su, Xiuyun; Hu, Nan; Hu, Jian; Li, Xiaowen; Yang, Jian‐Ming; Gao, Tianming

doi:10.1016/j.biopsych.2022.04.019

Cited by 30 publications

(16 citation statements)

References 70 publications

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“…Accordingly, we hypothesized that DEX inhibits the activation of A1 astrocytes but promotes A2 astrocyte polarization after neonatal HIBD through the inhibition of microglial activation. A2 astrocytes are widely recognized for their critical role in facilitating neurogenesis through the secretion of various neurotrophic factors, such as BDNF 52,53 . In our subsequent investigation, we employed the TrkB inhibitor ANA‐12 and AAV‐shBDNF to specifically examine the role of the BDNF/TrkB/CREB pathway in DEX‐induced neurogenesis and neuroprotection in neonatal rats after HIBD.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates cognitive impairment by promoting hippocampal neurogenesis via BDNF/TrkB/CREB signaling pathway in hypoxic–ischemic neonatal rats

Chen,

Wei

et al. 2023

CNS Neurosci Ther

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AimsDexmedetomidine (DEX) has been reported to alleviate hypoxic–ischemic brain damage (HIBD) in neonates. This study aimed to investigate whether DEX improves cognitive impairment by promoting hippocampal neurogenesis via the BDNF/TrkB/CREB signaling pathway in neonatal rats with HIBD.MethodsHIBD was induced in postnatal day 7 rats using the Rice‐Vannucci method, and DEX (25 μg/kg) was administered intraperitoneally immediately after the HIBD induction. The BDNF/TrkB/CREB pathway was regulated by administering the TrkB receptor antagonist ANA‐12 through intraperitoneal injection or by delivering adeno‐associated virus (AAV)‐shRNA‐BDNF via intrahippocampal injection. Western blot was performed to measure the levels of BDNF, TrkB, and CREB. Immunofluorescence staining was utilized to identify the polarization of astrocytes and evaluate the levels of neurogenesis in the dentate gyrus of the hippocampus. Nissl and TTC staining were performed to evaluate the extent of neuronal damage. The MWM test was conducted to evaluate spatial learning and memory ability.ResultsThe levels of BDNF and neurogenesis exhibited a notable decrease in the hippocampus of neonatal rats after HIBD, as determined by RNA‐sequencing technology. Our results demonstrated that treatment with DEX effectively increased the protein expression of BDNF and the phosphorylation of TrkB and CREB, promoting neurogenesis in the dentate gyrus of the hippocampus in neonatal rats with HIBD. Specifically, DEX treatment significantly augmented the expression of BDNF in hippocampal astrocytes, while decreasing the proportion of detrimental A1 astrocytes and increasing the proportion of beneficial A2 astrocytes in neonatal rats with HIBD. Furthermore, inhibiting the BDNF/TrkB/CREB pathway using either ANA‐12 or AAV‐shRNA‐BDNF significantly counteracted the advantageous outcomes of DEX on hippocampal neurogenesis, neuronal survival, and cognitive improvement.ConclusionsDEX promoted neurogenesis in the hippocampus by activating the BDNF/TrkB/CREB pathway through the induction of polarization of A1 astrocytes toward A2 astrocytes, subsequently mitigating neuronal damage and cognitive impairment in neonates with HIBD.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates cognitive impairment by promoting hippocampal neurogenesis via BDNF/TrkB/CREB signaling pathway in hypoxic–ischemic neonatal rats

Chen,

Wei

et al. 2023

CNS Neurosci Ther

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“…For instance, mice performance was found to be reduced in spontaneous alternation Y-maze and novel object replacement task when astrocytic Gq-GPCRs were specifically blocked, indicating an impaired working and short-term spatial memory ( Nagai et al, 2021 ). Moreover, recent fear memory, a form of long-term memory was found to be impaired when muscarinic acetylcholine receptor M1 (m1-AChRs) was specifically deleted in astrocytes from the dentate gyrus ( Li et al, 2022 ). It is interesting to note that astrocytic metabolism is required for learning activities.…”

Section: Astrocytic Regulation Of Neuronal Signals At the Network And...mentioning

confidence: 99%

Astrocytic modulation of neuronal signalling

Purushotham

Buskila

2023

Front. Netw. Physiol.

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Neuronal signalling is a key element in neuronal communication and is essential for the proper functioning of the CNS. Astrocytes, the most prominent glia in the brain play a key role in modulating neuronal signalling at the molecular, synaptic, cellular, and network levels. Over the past few decades, our knowledge about astrocytes and their functioning has evolved from considering them as merely a brain glue that provides structural support to neurons, to key communication elements. Astrocytes can regulate the activity of neurons by controlling the concentrations of ions and neurotransmitters in the extracellular milieu, as well as releasing chemicals and gliotransmitters that modulate neuronal activity. The aim of this review is to summarise the main processes through which astrocytes are modulating brain function. We will systematically distinguish between direct and indirect pathways in which astrocytes affect neuronal signalling at all levels. Lastly, we will summarize pathological conditions that arise once these signalling pathways are impaired focusing on neurodegeneration.

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“…The proliferation of adult hippocampal NSCs necessitates the adenosine 5-triphosphate (ATP) released from astrocytes (Cao et al, 2013). Additionally, Li et al found that astrocytes are involved in mediating the cholinergic regulation of adult hippocampal neurogenesis and memory through the CHRM1 receptor (Li, Su, et al, 2022). Moreover, astrocytes rely on Piezo1-mediated mechanotransduction mechanisms to regulate adult neurogenesis and cognitive functions (Chi et al, 2022).…”

Section: Neurogenic Niche and Neurotrophic Factorsmentioning

confidence: 99%

Adult neurogenesis research in China

Luo,

Xu,

Guo

2023

Dev Growth Differ

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Neural stem cells are multipotent stem cells that generate functional newborn neurons through a process called neurogenesis. Neurogenesis in the adult brain is tightly regulated and plays a pivotal role in the maintenance of brain function. Disruption of adult neurogenesis impairs cognitive function and is correlated with numerous neurologic disorders. Deciphering the mechanisms underlying adult neurogenesis not only advances our understanding of how the brain functions, but also offers new insight into neurologic diseases and potentially contributes to the development of effective treatments. The field of adult neurogenesis is experiencing significant growth in China. Chinese researchers have demonstrated a multitude of factors governing adult neurogenesis and revealed the underlying mechanisms of and correlations between adult neurogenesis and neurologic disorders. Here, we provide an overview of recent advancements in the field of adult neurogenesis due to Chinese scientists.

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Astrocytes Mediate Cholinergic Regulation of Adult Hippocampal Neurogenesis and Memory Through M1 Muscarinic Receptor

Cited by 30 publications

References 70 publications

Dexmedetomidine alleviates cognitive impairment by promoting hippocampal neurogenesis via BDNF/TrkB/CREB signaling pathway in hypoxic–ischemic neonatal rats

Dexmedetomidine alleviates cognitive impairment by promoting hippocampal neurogenesis via BDNF/TrkB/CREB signaling pathway in hypoxic–ischemic neonatal rats

Astrocytic modulation of neuronal signalling

Adult neurogenesis research in China

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