Drebrin depletion alters neurotransmitter receptor levels in protein complexes, dendritic spine morphogenesis and memory‐related synaptic plasticity in the mouse hippocampus

Abstract

Drebrin an actin-bundling key regulator of dendritic spine genesis and morphology, has been recently proposed as a regulator of hippocampal glutamatergic activity which is critical for memory formation and maintenance. Here, we examined the effects of genetic deletion of drebrin on dendritic spine and on the level of complexes containing major brain receptors. To this end, homozygous and heterozygous drebrin knockout mice generated in our laboratory and related wild-type control animals were studied. Level of protein complexes containing dopamine receptor D1/dopamine receptor D2, 5-hydroxytryptamine receptor 1A (5-HT1 A R), and 5-hydroxytryptamine receptor 7 (5-HT7R) were significantly reduced in hippocampus of drebrin knockout mice whereas no significant changes were detected for GluR1, 2, and 3 and NR1 as examined by native gel-based immunoblotting. Drebrin depletion also altered dendritic spine formation, morphology, and reduced levels of dopamine receptor D1 in dendritic spines as evaluated using immunohistochemistry/confocal microscopy. Electrophysiological studies further showed significant reduction in memory-related hippocampal synaptic plasticity upon drebrin depletion. These findings provide unprecedented experimental support for a role of drebrin in the regulation of memory-related synaptic plasticity and neurotransmitter receptor signaling, offer relevant information regarding the interpretation of previous studies and help in the design of future studies on dendritic spines.

The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia

“…Dbn −/+ mice were phenotypically indistinguishable from WT mice, and their Dbn −/− progeny lacked any Drebrin protein as demonstrated by immunoblotting (Figure 1B). Although Dbn −/− mice generated on a mixed genetic background were not reported to exhibit neonatal lethality, 8 our Dbn −/− mice on a C57BL/6 genetic background exhibited neonatal lethality for unclear reasons (Table 1). No gross anatomic defects were noted on necropsy.…”

“…6,7 Drebrin knockout mice were recently reported to exhibit decreased dendritic spine density, neurotransmitter receptor levels, and memory-related synaptic plasticity in hippocampal neurons when compared to WT mice. 8 Outside of the nervous system, Drebrin E expression has been reported in a variety of cell types. 9-11 …”

Danggui-Shaoyao-San, a Traditional Chinese Medicine, Relieved Depression and Cognitive Disorder Induced by Chronic Restraint Stress Involved in Regulating Dendritic Spines Remodeling

“…The results from behavioral, 321 electrophysiological and biochemical studies have shown that GluR1 involved in neuron 322 plasticity in brain regions including hippocampus, amygdala, striatum and cerebellum [54]. The 323 expression of BDNF and GluR1 were significantly down-regulated in hippocampus of CRS 324 group while those were significantly normalized by DSS (5 g/kg).…”

Down-Regulated Drebrin Aggravates Cognitive Impairments in a Mouse Model of Alzheimer’s Disease

“…The basic unit of information transmission between neurons is the synapse, which is composed of dendritic spines on the surface of dendrites and plays an important role in learning and memory [1,2]. The developmentally regulated brain protein drebrin (Dbn) contains adult type (Dbn A) and embryonic type (Dbn E) [3,4], distributed widely in the central nervous system and peripheral tissue.…”

“…Additionally, a noticeable reduction in memory-related hippocampal synaptic plasticity was found in electrophysiological studies of Dbn depleted mice. However, that was rarely reported in transgenic mice, and behavioral activities, cerebral glucose metabolism, or other indexes were rarely studied [2]. …”