Pvalb-KO Mouse

Pvalb, encoding the calcium-binding protein parvalbumin, is involved in multiple biological functions. It is associated with calcium ion sequestration and regulation, which can influence cellular processes such as mitochondrial function and endoplasmic reticulum stress response [6]. Pvalb-positive neurons are crucial components in certain neural circuits, playing roles in neurotransmission and neural modulation.

In mice, parvalbumin-positive neurons in the sensory thalamic reticular nucleus (sTRNPvalb) are essential for social memory. Inhibition of the PPCCaMKII→sTRNPvalb→PF circuit disrupts the ability to discriminate familiar from novel conspecifics, indicating the importance of sTRNPvalb neurons in this corticothalamic circuit for social memory [1]. In hepatocellular carcinoma (HCC), low expression of PVALB is an independent prognostic factor. Its absence accelerates tumor progression by regulating NK cell infiltration, as reduced PVALB expression attenuates the anticancer effect of NK cells via the Fas/FasL pathway [2]. In the context of major depressive disorder, chemogenetic inhibition of Pvalb + GABA interneurons in the mPFC of male mice produces antidepressant effects, while stimulation of these interneurons abolishes the antidepressant effects of scopolamine [3]. In Alzheimer's disease, there is a loss of Pvalb + inhibitory neuron subtypes in the later disease phase [4]. In airway function, vagal neurons expressing PVALB mediate airway closure responses, and ablating these neurons eliminates gasping in response to airway closure [5]. In follicular thyroid carcinoma cells, PVALB sequesters free cytoplasmic Ca(2+), alters mitochondrial features, and inhibits cell growth likely through the AKT/GSK-3β pathway [6]. In epilepsy, Pvalb-expressing GABAergic interneurons show significant transcriptomic changes, suggesting their involvement in epileptogenesis [7]. Also, the antidepressant actions of ketamine are blocked by GluN2B-NMDAR knockdown on Pvalb-expressing GABA interneurons in the mPFC [8].

In summary, Pvalb plays diverse and critical roles in various biological processes and disease conditions. Gene-knockout or conditional-knockout mouse models have been instrumental in revealing its functions in social memory, cancer progression, mood disorders, neurodegenerative diseases, airway reflexes, thyroid carcinoma cell behavior, and epilepsy. These studies enhance our understanding of the underlying mechanisms of these biological processes and diseases, potentially paving the way for novel therapeutic strategies.

References:

1. Wang, Feidi, Sun, Huan, Chen, Mingyue, Wang, Qiang, Li, Yan. 2024. The thalamic reticular nucleus orchestrates social memory. In Neuron, 112, 2368-2385.e11. doi:10.1016/j.neuron.2024.04.013. https://pubmed.ncbi.nlm.nih.gov/38701789/

2. Gong, Yiyang, Zhou, Minqin, Zhu, Yanting, Geng, Xitong, Huang, Da. 2024. PVALB Was Identified as an Independent Prognostic Factor for HCC Closely Related to Immunity, and Its Absence Accelerates Tumor Progression by Regulating NK Cell Infiltration. In Journal of hepatocellular carcinoma, 11, 813-838. doi:10.2147/JHC.S450479. https://pubmed.ncbi.nlm.nih.gov/38737383/

3. Fogaça, Manoela V, Wu, Min, Li, Chan, Picciotto, Marina R, Duman, Ronald S. 2020. Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses. In Molecular psychiatry, 26, 3277-3291. doi:10.1038/s41380-020-00916-y. https://pubmed.ncbi.nlm.nih.gov/33070149/

4. Gabitto, Mariano I, Travaglini, Kyle J, Rachleff, Victoria M, Keene, C Dirk, Lein, Ed S. 2024. Integrated multimodal cell atlas of Alzheimer's disease. In Nature neuroscience, 27, 2366-2383. doi:10.1038/s41593-024-01774-5. https://pubmed.ncbi.nlm.nih.gov/39402379/

5. Schappe, Michael S, Brinn, Philip A, Joshi, Narendra R, Zhang, Chuchu, Liberles, Stephen D. 2024. A vagal reflex evoked by airway closure. In Nature, 627, 830-838. doi:10.1038/s41586-024-07144-2. https://pubmed.ncbi.nlm.nih.gov/38448588/

6. Mendes, Thais Biude, Nozima, Bruno Heidi, Budu, Alexandre, Gazarini, Marcos Leoni, Cerutti, Janete Maria. 2016. PVALB diminishes [Ca2+] and alters mitochondrial features in follicular thyroid carcinoma cells through AKT/GSK3β pathway. In Endocrine-related cancer, 23, 769-82. doi:10.1530/ERC-16-0181. https://pubmed.ncbi.nlm.nih.gov/27458244/

7. Pfisterer, Ulrich, Petukhov, Viktor, Demharter, Samuel, Kharchenko, Peter V, Khodosevich, Konstantin. 2020. Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis. In Nature communications, 11, 5038. doi:10.1038/s41467-020-18752-7. https://pubmed.ncbi.nlm.nih.gov/33028830/

8. Gerhard, Danielle M, Pothula, Santosh, Liu, Rong-Jian, Wohleb, Eric S, Duman, Ronald S. . GABA interneurons are the cellular trigger for ketamine's rapid antidepressant actions. In The Journal of clinical investigation, 130, 1336-1349. doi:10.1172/JCI130808. https://pubmed.ncbi.nlm.nih.gov/31743111/