Recombinant BDNF Rescues Deficits in Basal Synaptic Transmission and Hippocampal LTP in BDNF Knockout Mice

Abstract

Brain-derived neurotrophic factor (BDNF) is expressed at high levels in hippocampal neurons, and its expression is modulated by neural activity. Knockout mice can be used to study the roles of molecules like BDNF in synaptic plasticity with more molecular specificity than is possible using pharmacological approaches. Because in conventional knockouts the disrupted gene product is absent in all tissues throughout the life of the animal, developmental effects may complicate the interpretation of deficits in the adult. Rescue experiments can help to distinguish between developmental and acute requirements for the missing gene product. We here demonstrate that treatment of hippocampal slices from BDNF knockout mice with recombinant BDNF completely reverses deficits in long-term potentiation and significantly improves deficits in basal synaptic transmission at the Schaffer collateral-CA1 synapse. Thus, BDNF has an acute role in hippocampal synaptic function.

Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats

“…Collagen I and fibronectin may be involved in hMSC-induced functional improvement. At 6 weeks postgrafting, the latest time point of the present study, the grafted MSCs still maintained their primitive properties producing collagen I and fibronectin (41,44). Numerous studies have shown that extracellular matrix (ECM) proteins influence cell proliferation, migration, survival, and differentiation (20,21,46,58).…”

“…Numerous studies suggest that neurotrophic factors play important roles in brain plasticity. Neurotrophic factors can enhance neuronal sprouting (11), synaptogenesis (18), long-term potentiation (2,30,41), and neurotransmission (25) and increase neurotransmitter release (26,27,34). Humpel et al reported that human fetal cortical grafts expressed nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 mRNA after transplantation to cortical cavities in rats (23).…”

Downregulation of BDNF mRNA in the Hippocampal Dentate Gyrus after Re-exposure to Cues Previously Associated with Footshock,

“…Also of possible pertinence to such clinical neuropsychiatric disorders, BDNF has been shown to be essential to long-term potentiation (LTP), a cellular process proposed to underly learning and memory (Patterson et al 1996). Consistent with a role for BDNF in learning, rats pre-treated with anti-BDNF antibodies show impairments in spatial learning and memory (Mu et al 1999).…”

“…Alternatively, it is possible that stressinduced decreases in hippocampal BDNF levels may underly disturbances in memory and cognition common to several disorders that may otherwise vary in their etiology and symptom profiles (Wolfe and Schlesinger 1997;Yousef et al 1998). Also of possible pertinence to such clinical neuropsychiatric disorders, BDNF has been shown to be essential to long-term potentiation (LTP), a cellular process proposed to underly learning and memory (Patterson et al 1996). Consistent with a role for BDNF in learning, rats pre-treated with anti-BDNF antibodies show impairments in spatial learning and memory (Mu et al 1999).…”

“…BDNF as well as these other neurotrophins, plays an important role in neuronal growth and differentiation during development, and also contributes to the survival, function, and plasticity of neurons in the adult brain (Lewin and Barde 1996). Thus, through a variety of mechanisms in different brain regions, BDNF has been implicated in emergent phenomena such as learning and memory (Patterson et al 1996;Mu et al 1999) and even contributes to the modulation of overt behaviors such as aggression (Lyons et al 1999). The ability of BDNF to influence these processes is related, in part, to the activity dependent regulation of BDNF expression in adult brain (Lewin and Barde 1996).…”