Overexpression of α-Klotho isoforms promotes distinct Effects on BDNF-Induced Alterations in Dendritic Morphology

• DOI: 10.1007/s12035-024-04171-y
• Publication Date: 2024-04-09T03:41:11Z
• Authors: Marina Minto Cara...; Ratchell Sadovnik; Allen Fu; Shradha Suresh; Srinivasa Gandu; Bonnie L. Firestein
• Keywords: Klotho

Abstract α-Klotho (α-Kl) is a modulator of aging, neuroprotection, and cognition. Transcription the Klotho gene produces two splice variants—a membrane protein (mKl), which can be cleaved released into extracellular milieu, truncated secreted form (sKl). Despite mounting evidence supporting role for α-Kl in brain function, specific roles isoforms neuronal development remain elusive. Here, we examined levels rat observed region-specific expression adult that differs between isoforms. In developing hippocampus, decrease after third postnatal week, marking end critical period development. We overexpressed primary cultures cortical neurons evaluated effects on brain-derived neurotrophic factor (BDNF) signaling. Overexpression either isoform attenuated BDNF-mediated signaling reduced intracellular Ca 2+ levels, with mKl promoting greater effect. or sKl overexpression hippocampal resulted partially overlapping reduction secondary dendrite branching. Moreover, increased number. BDNF treatment overexpressing branching phenotype similar to control neurons. mKl, restored higher order dendrites close, but not distal, soma. Taken together, data presented support idea play distinct development, specifically, morphogenesis.