Table 4.
Top candidate age-associated spatial learning impairment (ASLI) hub genes in the yellow module of the R7 dataset.
| Hub gene | Function description | Reference |
|---|---|---|
| Camk1g | Encodes a protein similar to calcium/calmodulin-dependent protein kinase (CaMK), but its exact function is not known. CaMKs activated by the neuronal Ca2+ influx phosphorylate cyclic adenosine monophosphate (cAMP) responsive element binding protein (CREB), which has been implicated in spatial learning and memory formation. | Thomas and Huganir (2004) and Voglis and Tavernarakis (2006) |
| Cdk5r1* | Involved in the pathology of Alzheimer’s disease through the deregulated activity of cyclin-dependent kinase 5 (Cdk5), and also involved in synaptic plasticity, and learning and memory. | Angelo et al. (2006) and Shukla et al. (2012) |
| Cntn1 | Contributes to the formation and function of neuronal connections, axon-glia communication, and necessary for myelin sheath formation by oligodendrocytes. | Ranscht (1988) and Çolakoğlu et al. (2014) |
| Dlg3* | Encodes a member of the membrane-associated guanylate kinase protein family; may play a role in clustering of N-methyl-D-aspartate (NMDA) receptors at excitatory synapses. It is highly enriched in the postsynaptic density (PSD), and plays essential roles in synaptic organization and plasticity. | Elias and Nicoll (2007), Elias et al. (2008) and Wei et al. (2015) |
| Dpp6 | Encodes an auxiliary subunit of voltage-gated potassium-4 channels and regulates the A-type K+ current gradient, which regulates dendritic excitability. | Nadal et al. (2003) and Wolf et al. (2014) |
| Eif5 | Make 80S ribosomal initiation complex functional for translation. | Si et al. (1996) |
| Gabrg1 | Belongs to the ligand-gated ionic channel family. It is an integral membrane protein and plays an important role in inhibiting neurotransmission. | Pirker et al. (2000) and Ye and Carew (2010) |
| Kcnab2* | Encodes one of the beta subunits of the shaker-related Kv channels (Kv1.1 to Kv1.8) and found as a component of almost all potassium channel complexes containing Kv1 α subunits. It is a learning gene that is known to contribute to certain types of learning | Voglis and Tavernarakis (2006) and McKeown et al. (2008) |
| Mapk1* | Encodes a member of the MAP kinase family and is known as a learning gene. Hippocampal expression of Mapk1 is essential for synaptic plasticity and spatial learning. | Selcher et al. (2001), Sweatt (2001) and Thomas and Huganir (2004) |
| Mapre1 | It is involved in the regulation of microtubule structures and chromosome stability. | Tirnauer et al. (2002) and Kim et al. (2013) |
| Ndfip2 | Affects receptor tyrosine kinase signaling by ubiquitinating several key components of the signaling pathways through binding to E3 ubiquitin ligases. | Cristillo et al. (2003) and Mund and Pelham (2010) |
| Ppp2r2c | Ppp2r2c gene encodes one of the four B regulatory subunits of the protein phosphatase 2A (PP2A) enzyme complex. Inhibition of PP2A by inhibitor I1PP2A results in deficits in spatial reference memory and memory consolidation in adult rats. | Xu et al. (2006) and Backx et al. (2010) |
| Prkacb | Encodes the catalytic beta subunit of protein kinase A (PKA). PKA activates CREB and contributes to learning induced gene expression. Prkacb expression is required for LTP in the Hippocampus. | Qi et al. (1996), Howe et al. (2002) and Nguyen and Woo (2003) |
| Pten* | It modulates activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. PTEN independently controls the structural and functional properties of hippocampal synapses and plays a direct role in activity-dependent hippocampal synaptic plasticity such as LTP and LTD. | Maehama and Dixon (1998), Blair and Harvey (2012) and Sperow et al. (2012) |
| Rasgrp1 | It is a guanine nucleotide-exchange factor. When it is activated by Ca2+/calmodulin and diacylglycerol (DAG), it facilitates exchange of GDP to GTP and activates Ras. | Stone (2006) |
| Scn2b | Scn2b is a complex glycoprotein comprised of an alpha subunit and often one to several beta subunits. It was reported to have a role in epilepsy. | Baum et al. (2014) and XiYang et al. (2016) |
| Stxbp1 | Plays a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. | Kurps and de Wit (2012) |
Genes with an “*” were also identified as learning genes in a previous meta-analysis (Uddin and Singh, 2013). Legend: Camk1g, Calcium/calmodulin-dependent protein kinase I gamma; Cdk5r1, Cyclin-dependent kinase 5, regul. subunit 1 (p35); Cntn1, Contactin 1; Dlg3, Discs, large homolog 3; Dlgap1, Discs, large homolog-associated protein 1; Dpp6, Dipeptidyl-peptidase 6; Eif5, Eukaryotic translation initiation factor 5; Gabrg1, Gamma-aminobutyric acid (GABA) A receptor, gamma 1; Impact, Impact RWD domain protein (RWDD5); Kcnab2, Potassium channel, voltage gated shaker related subfamily A regulatory beta subunit 2; Mapk1, Mitogen-activated protein kinase 1 (ERK); Mapre1, Microtubule-associated protein, RP/EB family, member 1; Ndfip2, Nedd4 family interacting protein 2; Ppp2r2c, Protein phosphatase 2, regulatory subunit B, gamma; Prkacb, Protein kinase, cAMP-dependent, catalytic, beta; Pten, Phosphatase and tensin homolog; Rasgrp1, RAS guanyl releasing protein 1 (calcium and DAG-regulated); Scn2b, Sodium channel, voltage-gated, type II, beta; Stxbp1, Syntaxin binding protein 1.