瘤抑制剂p53调节活动依赖的突触强化,自闭症类行为和海马依赖的学习
Kwan Young Lee1, Haohan Wang2, Yeeun Yook3
1Department of Molecular and Integrative Physiology, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. lky@illinois.edu.
Molecular psychiatry
|September 27, 2023
概括
瘤抑制剂p53是一种新型的转录因子,对突触可塑性和依赖海马的学习和记忆至关重要. 它还抑制了类似自闭症的行为,在小鼠中观察到性别特异性的效应.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 行为遗传学 行为遗传学
背景情况:
- 突触强化对行为至关重要,并依赖于转录因子.
- 瘤抑制剂p53在突触可塑性和行为的作用在很大程度上是未知的.
研究的目的:
- 研究p53在突触强化,学习和行为中的作用.
- 为了确定参与这些过程的p53调节基因.
主要方法:
- 在初级神经元中,化学诱导的长期强化 (cLTP).
- 在小鼠中,前脑特异性降低了p53.
- 行为测试 (运动,焦虑,重复行为,社交能力).
- 海马长期增强 (LTP) 的评估.
- 河马组织的RNA测序 (RNAseq).
主要成果:
- 在cLTP时,p53水平增加,并且对于AMPA受体表面表达是必需的.
- 在小鼠中,p53 knockdown促进了重复行为,降低了社交能力,并损害了海马体LTP和记忆力.
- 在雄性小鼠中,学习缺陷更严重,这表明性别特异性的影响.
- RNAseq确定了参与突触可塑性和神经发育的p53-调节基因.
结论:
- p53作为一种活动依赖的转录因子,调节AMPA受体表面表达.
- p53对海马突触可塑性,学习和记忆至关重要.
- p53在抑制自闭症类行为方面发挥作用,并对学习和记忆表现出性别特异性影响.
相关概念视频
Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
Loss of Tumor Suppressor Gene Functions
4.9K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.9K
DNA Damage can Stall the Cell Cycle
9.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K
Long-term Potentiation
2.8K
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Hebbian LTP
LTP can occur when...
Hebbian LTP
LTP can occur when...
2.8K
Cancer-Critical Genes II: Tumor Suppressor Genes
7.5K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.5K


