Tafa-2 plays an essential role in neuronal survival and neurobiological function in mice

Abstract

Tafa is a family of small secreted proteins with conserved cysteine residues and restricted expression in the brain. It is composed of five highly homologous genes referred to as Tafa-1 to -5. Among them, Tafa-2 is identified as one of the potential genes responsible for intellectual deficiency in a patient with mild mental retardation. To investigate the biological function of Tafa-2 in vivo, Tafa-2 knockout mice were generated. The mutant mice grew and developed normally but exhibited impairments in spatial learning and memory in Morris water maze test and impairments in short- and long-term memory in novel object recognition test, accompanied with increased level of anxiety-like behaviors in open-field test and elevated plus maze test, and decreased level of depression-like behaviors in forced-swim test and tail-suspension test. Further examinations revealed that Tafa-2 deficiency causes severe neuronal reduction and increased apoptosis in the brain of Tafa-2−/− mice via downregulation of PI3K/Akt and MAPK/Erk pathways. Conformably, the expression levels of CREB target genes including BDNF, c-fos and NF1, and CBP were found to be reduced in the brain of Tafa-2−/− mice. Taken together, our data indicate that Tafa-2 may function as a neurotrophic factor essential for neuronal survival and neurobiological functions.

Association of Serum FAM19A5 with Cognitive Impairment in Vascular Dementia

“…Emerging evidence has indicated that FAM19A family is involved in the pathological mechanism of cognition. FAM19A2 knockout mice exhibited decline in short-term and long-term memory via novel object recognition test and decline in spatial learning and memory via the Morris water maze (MWM) test [26,27]. However, FAM19A1 knockout mice only exhibited reduced anxiety and sensitivity to pain, and spatial learning and exploration are preserved [28,29].…”

Peptide ligands targeting FGF receptors promote recovery from dorsal root crush injury via AKT/mTOR signaling

“…These results suggested that the increased axon outgrowth by CH02 primarily depended on regulating AKT signaling downstream of FGFRs. Since ERK and AKT as pro-survival signaling molecules were implicated in regulating neuronal survival 66 - 69 , we determined whether CH02- mediated-enhanced neuron survival depended on the AKT or ERK signal downstream of FGFRs. We observed that both AKTi and U0126 significantly reduced the protective effect of CH02 on neurons from apoptosis induced by H 2 O 2 (Figure 6 M-N).…”

Peruvian Newborn Male with 3p13 Deletion Syndrome Encompassing the FOXP1 Gene: Review of the Literature

“…FAM19A1 is a ligand for GPR1 (G protein-coupled receptor 1), that has a function in the proliferation and self-renewal of neural stem cells. [22][23][24] The FAM19A1 gene has a HI of 8%; consequently, this partial deletion could contribute to development delay and hypotonia.…”